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Cannabis Use Linked to Brain Thinning in Adolescents
, research in mice and humans suggested.
The multilevel study demonstrated that tetrahydrocannabinol (THC), an active substance in cannabis, causes shrinkage of dendritic arborization — the neurons’ network of antennae that play a critical role in communication between brain cells.
The connection between dendritic arborization and cortical thickness was hinted at in an earlier study by Tomáš Paus, MD, PhD, professor of psychiatry and addictology at the University of Montreal, Quebec, Canada, and colleagues, who found that cannabis use in early adolescence was associated with lower cortical thickness in boys with a high genetic risk for schizophrenia.
“We speculated at that time that the differences in cortical thickness might be related to differences in dendritic arborization, and our current study confirmed it,” Paus said.
That confirmation came in the mouse part of the study, when coauthor Graciela Piñeyro, MD, PhD, also of the University of Montreal, counted the dendritic branches of mice exposed to THC and compared the total with the number of dendritic branches in unexposed mice. “What surprised me was finding that THC in the mice was targeting the same type of cells and structures that Dr. Paus had predicted would be affected from the human studies,” she said. “Structurally, they were mostly the neurons that contribute to synapses in the cortex, and their branching was reduced.”
Paus explained that in humans, a decrease in input from the affected dendrites “makes it harder for the brain to learn new things, interact with people, cope with new situations, et cetera. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”
The study was published online on October 9 in the Journal of Neuroscience.
Of Mice, Men, and Cannabis
Although associations between cannabis use by teenagers and variations in brain maturation have been well studied, the cellular and molecular underpinnings of these associations were unclear, according to the authors.
To investigate further, they conducted this three-step study. First, they exposed adolescent male mice to THC or a synthetic cannabinoid (WIN 55,212-2) and assessed differentially expressed genes, spine numbers, and the extent of dendritic complexity in the frontal cortex of each mouse.
Next, using MRI, they examined differences in cortical thickness in 34 brain regions in 140 male adolescents who experimented with cannabis before age 16 years and 327 who did not.
Then, they again conducted experiments in mice and found that 13 THC-related genes correlated with variations in cortical thickness. Virtual histology revealed that these 13 genes were coexpressed with cell markers of astrocytes, microglia, and a type of pyramidal cell enriched in genes that regulate dendritic expression.
Similarly, the WIN-related genes correlated with differences in cortical thickness and showed coexpression patterns with the same three cell types.
Furthermore, the affected genes were also found in humans, particularly in the thinner cortical regions of the adolescents who experimented with cannabis.
By acting on microglia, THC seems to promote the removal of synapses and, eventually, the reduction of the dendritic tree in mice, Piñeyro explained. That’s important not only because a similar mechanism may be at work in humans but also because “we now might have a model to test different types of cannabis products to see which ones are producing the greatest effect on neurons and therefore greater removal of synapses through the microglia. This could be a way of testing drugs that are out in the street to see which would be the most or least dangerous to the synapses in the brain.”
‘Significant Implications’
Commenting on the study, Yasmin Hurd, PhD, Ward-Coleman chair of translational neuroscience at the Icahn School of Medicine at Mount Sinai and director of the Addiction Institute of Mount Sinai in New York City, said, “These findings are in line with previous results, so they are feasible. This study adds more depth by showing that cortical genes that were differentially altered by adolescent THC correlated with cannabis-related changes in cortical thickness based on human neuroimaging data.” Hurd did not participate in the research.
“The results emphasize that consumption of potent cannabis products during adolescence can impact cortical function, which has significant implications for decision-making and risky behavior as well. It also can increase vulnerability to psychiatric disorders such as schizophrenia.”
Although a mouse model is “not truly the same as the human condition, the fact that the animal model also showed evidence of the morphological changes indicative of reduced cortical thickness, [like] the humans, is strong,” she said.
Additional research could include women and assess potential sex differences, she added.
Ronald Ellis, MD, PhD, an investigator in the Center for Medicinal Cannabis Research at the University of California, San Diego School of Medicine, said, “The findings are plausible and extend prior work showing evidence of increased risk for psychotic disorders later in life in adolescents who use cannabis.” Ellis did not participate in the research.
“Future studies should explore how these findings might vary across different demographic groups, which could provide a more inclusive understanding of how cannabis impacts the brain,” he said. “Additionally, longitudinal studies to track changes in the brain over time could help to establish causal relationships more robustly.
“The take-home message to clinicians at this point is to discuss cannabis use history carefully and confidentially with adolescent patients to better provide advice on its potential risks,” he concluded.
Paus added that he would tell patients, “If you’re going to use cannabis, don’t start early. If you have to, then do so in moderation. And if you have family history of mental illness, be very careful.”
No funding for the study was reported. Paus, Piñeyro, Hurd, and Ellis declared having no relevant financial relationships.
A version of this article appeared on Medscape.com.
, research in mice and humans suggested.
The multilevel study demonstrated that tetrahydrocannabinol (THC), an active substance in cannabis, causes shrinkage of dendritic arborization — the neurons’ network of antennae that play a critical role in communication between brain cells.
The connection between dendritic arborization and cortical thickness was hinted at in an earlier study by Tomáš Paus, MD, PhD, professor of psychiatry and addictology at the University of Montreal, Quebec, Canada, and colleagues, who found that cannabis use in early adolescence was associated with lower cortical thickness in boys with a high genetic risk for schizophrenia.
“We speculated at that time that the differences in cortical thickness might be related to differences in dendritic arborization, and our current study confirmed it,” Paus said.
That confirmation came in the mouse part of the study, when coauthor Graciela Piñeyro, MD, PhD, also of the University of Montreal, counted the dendritic branches of mice exposed to THC and compared the total with the number of dendritic branches in unexposed mice. “What surprised me was finding that THC in the mice was targeting the same type of cells and structures that Dr. Paus had predicted would be affected from the human studies,” she said. “Structurally, they were mostly the neurons that contribute to synapses in the cortex, and their branching was reduced.”
Paus explained that in humans, a decrease in input from the affected dendrites “makes it harder for the brain to learn new things, interact with people, cope with new situations, et cetera. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”
The study was published online on October 9 in the Journal of Neuroscience.
Of Mice, Men, and Cannabis
Although associations between cannabis use by teenagers and variations in brain maturation have been well studied, the cellular and molecular underpinnings of these associations were unclear, according to the authors.
To investigate further, they conducted this three-step study. First, they exposed adolescent male mice to THC or a synthetic cannabinoid (WIN 55,212-2) and assessed differentially expressed genes, spine numbers, and the extent of dendritic complexity in the frontal cortex of each mouse.
Next, using MRI, they examined differences in cortical thickness in 34 brain regions in 140 male adolescents who experimented with cannabis before age 16 years and 327 who did not.
Then, they again conducted experiments in mice and found that 13 THC-related genes correlated with variations in cortical thickness. Virtual histology revealed that these 13 genes were coexpressed with cell markers of astrocytes, microglia, and a type of pyramidal cell enriched in genes that regulate dendritic expression.
Similarly, the WIN-related genes correlated with differences in cortical thickness and showed coexpression patterns with the same three cell types.
Furthermore, the affected genes were also found in humans, particularly in the thinner cortical regions of the adolescents who experimented with cannabis.
By acting on microglia, THC seems to promote the removal of synapses and, eventually, the reduction of the dendritic tree in mice, Piñeyro explained. That’s important not only because a similar mechanism may be at work in humans but also because “we now might have a model to test different types of cannabis products to see which ones are producing the greatest effect on neurons and therefore greater removal of synapses through the microglia. This could be a way of testing drugs that are out in the street to see which would be the most or least dangerous to the synapses in the brain.”
‘Significant Implications’
Commenting on the study, Yasmin Hurd, PhD, Ward-Coleman chair of translational neuroscience at the Icahn School of Medicine at Mount Sinai and director of the Addiction Institute of Mount Sinai in New York City, said, “These findings are in line with previous results, so they are feasible. This study adds more depth by showing that cortical genes that were differentially altered by adolescent THC correlated with cannabis-related changes in cortical thickness based on human neuroimaging data.” Hurd did not participate in the research.
“The results emphasize that consumption of potent cannabis products during adolescence can impact cortical function, which has significant implications for decision-making and risky behavior as well. It also can increase vulnerability to psychiatric disorders such as schizophrenia.”
Although a mouse model is “not truly the same as the human condition, the fact that the animal model also showed evidence of the morphological changes indicative of reduced cortical thickness, [like] the humans, is strong,” she said.
Additional research could include women and assess potential sex differences, she added.
Ronald Ellis, MD, PhD, an investigator in the Center for Medicinal Cannabis Research at the University of California, San Diego School of Medicine, said, “The findings are plausible and extend prior work showing evidence of increased risk for psychotic disorders later in life in adolescents who use cannabis.” Ellis did not participate in the research.
“Future studies should explore how these findings might vary across different demographic groups, which could provide a more inclusive understanding of how cannabis impacts the brain,” he said. “Additionally, longitudinal studies to track changes in the brain over time could help to establish causal relationships more robustly.
“The take-home message to clinicians at this point is to discuss cannabis use history carefully and confidentially with adolescent patients to better provide advice on its potential risks,” he concluded.
Paus added that he would tell patients, “If you’re going to use cannabis, don’t start early. If you have to, then do so in moderation. And if you have family history of mental illness, be very careful.”
No funding for the study was reported. Paus, Piñeyro, Hurd, and Ellis declared having no relevant financial relationships.
A version of this article appeared on Medscape.com.
, research in mice and humans suggested.
The multilevel study demonstrated that tetrahydrocannabinol (THC), an active substance in cannabis, causes shrinkage of dendritic arborization — the neurons’ network of antennae that play a critical role in communication between brain cells.
The connection between dendritic arborization and cortical thickness was hinted at in an earlier study by Tomáš Paus, MD, PhD, professor of psychiatry and addictology at the University of Montreal, Quebec, Canada, and colleagues, who found that cannabis use in early adolescence was associated with lower cortical thickness in boys with a high genetic risk for schizophrenia.
“We speculated at that time that the differences in cortical thickness might be related to differences in dendritic arborization, and our current study confirmed it,” Paus said.
That confirmation came in the mouse part of the study, when coauthor Graciela Piñeyro, MD, PhD, also of the University of Montreal, counted the dendritic branches of mice exposed to THC and compared the total with the number of dendritic branches in unexposed mice. “What surprised me was finding that THC in the mice was targeting the same type of cells and structures that Dr. Paus had predicted would be affected from the human studies,” she said. “Structurally, they were mostly the neurons that contribute to synapses in the cortex, and their branching was reduced.”
Paus explained that in humans, a decrease in input from the affected dendrites “makes it harder for the brain to learn new things, interact with people, cope with new situations, et cetera. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”
The study was published online on October 9 in the Journal of Neuroscience.
Of Mice, Men, and Cannabis
Although associations between cannabis use by teenagers and variations in brain maturation have been well studied, the cellular and molecular underpinnings of these associations were unclear, according to the authors.
To investigate further, they conducted this three-step study. First, they exposed adolescent male mice to THC or a synthetic cannabinoid (WIN 55,212-2) and assessed differentially expressed genes, spine numbers, and the extent of dendritic complexity in the frontal cortex of each mouse.
Next, using MRI, they examined differences in cortical thickness in 34 brain regions in 140 male adolescents who experimented with cannabis before age 16 years and 327 who did not.
Then, they again conducted experiments in mice and found that 13 THC-related genes correlated with variations in cortical thickness. Virtual histology revealed that these 13 genes were coexpressed with cell markers of astrocytes, microglia, and a type of pyramidal cell enriched in genes that regulate dendritic expression.
Similarly, the WIN-related genes correlated with differences in cortical thickness and showed coexpression patterns with the same three cell types.
Furthermore, the affected genes were also found in humans, particularly in the thinner cortical regions of the adolescents who experimented with cannabis.
By acting on microglia, THC seems to promote the removal of synapses and, eventually, the reduction of the dendritic tree in mice, Piñeyro explained. That’s important not only because a similar mechanism may be at work in humans but also because “we now might have a model to test different types of cannabis products to see which ones are producing the greatest effect on neurons and therefore greater removal of synapses through the microglia. This could be a way of testing drugs that are out in the street to see which would be the most or least dangerous to the synapses in the brain.”
‘Significant Implications’
Commenting on the study, Yasmin Hurd, PhD, Ward-Coleman chair of translational neuroscience at the Icahn School of Medicine at Mount Sinai and director of the Addiction Institute of Mount Sinai in New York City, said, “These findings are in line with previous results, so they are feasible. This study adds more depth by showing that cortical genes that were differentially altered by adolescent THC correlated with cannabis-related changes in cortical thickness based on human neuroimaging data.” Hurd did not participate in the research.
“The results emphasize that consumption of potent cannabis products during adolescence can impact cortical function, which has significant implications for decision-making and risky behavior as well. It also can increase vulnerability to psychiatric disorders such as schizophrenia.”
Although a mouse model is “not truly the same as the human condition, the fact that the animal model also showed evidence of the morphological changes indicative of reduced cortical thickness, [like] the humans, is strong,” she said.
Additional research could include women and assess potential sex differences, she added.
Ronald Ellis, MD, PhD, an investigator in the Center for Medicinal Cannabis Research at the University of California, San Diego School of Medicine, said, “The findings are plausible and extend prior work showing evidence of increased risk for psychotic disorders later in life in adolescents who use cannabis.” Ellis did not participate in the research.
“Future studies should explore how these findings might vary across different demographic groups, which could provide a more inclusive understanding of how cannabis impacts the brain,” he said. “Additionally, longitudinal studies to track changes in the brain over time could help to establish causal relationships more robustly.
“The take-home message to clinicians at this point is to discuss cannabis use history carefully and confidentially with adolescent patients to better provide advice on its potential risks,” he concluded.
Paus added that he would tell patients, “If you’re going to use cannabis, don’t start early. If you have to, then do so in moderation. And if you have family history of mental illness, be very careful.”
No funding for the study was reported. Paus, Piñeyro, Hurd, and Ellis declared having no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM THE JOURNAL OF NEUROSCIENCE
Obesity Therapies: What Will the Future Bring?
“Obesity only recently caught the public’s attention as a disease,” Matthias Blüher, MD, professor of medicine at the Leipzig University and director of the Helmholtz Institute for Metabolism, Obesity and Vascular Research, Leipzig, Germany, told attendees in a thought-provoking presentation at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.
Even though the attitudes around how obesity is perceived may be relatively new, Blüher believes they are nonetheless significant. As a sign of how the cultural headwinds have shifted, he noted the 2022 film The Whale, which focuses on a character struggling with obesity. As Blüher pointed out, not only did the film’s star, Brendan Fraser, receive an Academy Award for his portrayal but he also theorized that the majority of celebrities in the audience were likely taking new weight loss medications.
“I strongly believe that in the future, obesity treatment will carry less stigma. It will be considered not as a cosmetic problem, but as a progressive disease.”
He sees several changes in the management of obesity likely to occur on the near horizon, beginning with when interventions directed at treating it will begin.
Obesity treatment should start at a young age, he said, because if you have overweight at ages 3-6 years, the likelihood of becoming an adult with obesity is approximately 90%. “Looking ahead, shouldn’t we put more emphasis on this age group?”
Furthermore, he hopes that clinical trials will move beyond body weight and body mass index (BMI) as their main outcome parameters. Instead, “we should talk about fat distribution, fat or adipose tissue function, muscle loss, body composition, and severity of disease.”
Blüher pointed to the recently published framework for the diagnosis, staging, and management of obesity in adults put forward by the European Association for the Study of Obesity. It states that obesity should be staged not based on BMI or body weight alone but also on an individual›s medical, functional, and psychological (eg, mental health and eating behavior) status.
“The causes of obesity are too complex to be individually targeted,” he continued, unlike examples such as hypercholesterolemia or smoking cessation, where clinicians may have one target to address.
“But overeating, slow metabolism, and low physical activity involve socio-cultural factors, global food marketing, and many other factors. Therefore, clinicians should be setting health targets, such as improving sleep apnea and improving physical functioning, rather than a kilogram number.”
Three Pillars of Treatment
Right now, clinicians have three pillars of treatments available, Blüher said. The first is behavioral intervention, including strategies such as counseling, diet, exercise, self-monitoring, stress management, and sleep management.
“We know that these behavioral aspects typically lack adherence and effect size, but they’re important, and for a certain group of people, they may be the best and safest treatment.”
The second pillar is pharmacotherapy, and the third is surgery.
Each pillar poses questions for future research, he explained.
“First, do we really need more evidence that behavioral interventions typically fail in the long run and are prone to rebound of body weight and health issues? No. Or which diet is best? We have hundreds of diet interventions, all of which basically show very similar outcomes. They lead to an average weight loss of 3% to 5% and do improve health conditions associated with obesity.”
When it comes to pharmacotherapies, Blüher does believe clinicians need more options.
Depending on affordability and access, glucagon-like peptide 1 (GLP-1) semaglutide will likely become the first-line therapy for most people living with obesity who want to take medications, he suggested. The dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide will be reserved for those with more severe conditions.
“But this is not the end of the story,” he said. “The pipelines for obesity pharmacotherapies are full, and they have different categories. We are optimistic that we will have more therapies not only for type 2 diabetes (T2D) but also for obesity. Combinations such as CagriSema (cagrilintide + semaglutide, currently indicated for T2D) may outperform the monotherapies. We have to see if they’re as safe, and we have to wait for phase 3 trials and long-term outcomes.”
“The field is open for many combinations, ideas and interactions among the incretin-based signaling systems, but personally, I think that the triple agonists have a very bright future,” Blüher said.
For example, retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors, showed promise in a phase 2 trial. Although that was not a comparative study, “the average changes in body weight suggest that in a dose-dependent manner, you can expect even more weight loss than with tirzepatide.”
Treating the Causes
The future of obesity therapy might also be directed at the originating factors that cause it, Blüher suggested, adding that “treating the causes is a dream of mine.”
One example of treating the cause is leptin therapy, as shown in a 1999 study of recombinant leptin in a child with congenital leptin deficiency. A more recent example is setmelanotide treatment for proopiomelanocortin deficiency.
“We are at the beginning for these causative treatments of obesity, and I hope that the future will hold much more of these insights and targets, as in cancer therapy.”
“Finally,” he said, “We eat with our brain. And so in the future, we also will be better able to use our knowledge about the complex neural circuits that are obesogenic, and how to target them. In doing so, we can learn from surgeons because obesity surgery is very effective in changing the anatomy, and we also observe hormonal changes. We see that ghrelin, GLP-1, peptide YY, and many others are affected when the anatomy changes. Why can’t we use that knowledge to design drugs that resemble or mimic the effect size of bariatric surgery?”
And that goes to the third pillar of treatment and the question of whether the new weight loss drugs may replace surgery, which also was the topic of another EASD session.
Blüher doesn’t see that happening for at least a decade, given that there is still an effect-size gap between tirzepatide and surgery, especially for individuals with T2D. In addition, he noted, there will still be nonresponders to drugs, and clinicians are not treating to target yet. Looking ahead, he foresees a combination of surgery and multi-receptor agonists.
“I believe that obesity won’t be cured in the future, but we will have increasingly better lifelong management with a multidisciplinary approach, although behavioral interventions still will not be as successful as pharmacotherapy and bariatric surgery,” he concluded.
Q&A
During the question-and-answer session following his lecture, several attendees asked Blüher for his thoughts around other emerging areas in this field. One wanted to know whether microbiome changes might be a future target for obesity treatment.
“So far, we don’t really understand which bacteria, which composition, at which age, and at which part of the intestine need to be targeted,” Blüher responded. “Before we know that mechanistically, I think it would be difficult, but it could be an avenue to go for, though I’m a little less optimistic about it compared to other approaches.”
Given that obesity is not one disease, are there cluster subtypes, as for T2D — eg, the hungry brain, the hungry gut, low metabolism — that might benefit from individualized treatment, another attendee asked.
“We do try to subcluster people living with obesity,” Blüher said. “We did that based on adipose tissue expression signatures, and indeed there is large heterogeneity. But we are far from addressing the root causes and all subtypes of the disease, and that would be a requirement before we could personalize treatment in that way.”
Next, an attendee asked what is responsible for the differential weight loss in people with diabetes and people without? Blüher responded that although he doesn’t have the answer, he does have hypotheses.
“One could be that the disease process — eg, deterioration of beta cell function, of the balance of hormones such as insulin and leptin, of inflammatory parameters, of insulin resistance — is much more advanced in diseases such as T2D and sleep apnea. Maybe it then takes more to address comorbid conditions such as inflammation and insulin resistance. Therefore, combining current therapies with insulin sensitizers, for example, could produce better results.”
What about using continuous glucose monitoring to help people stick to their diet?
“That’s an important question that speaks to personalized treatment,” he said. “It applies not only to continuous glucose monitoring but also to nutrition and other modes of self-monitoring, which seem to be among the most successful tools for long-term weight maintenance.”
Blüher finished by saying, “As we look into the future, I hope that there will be better approaches for all aspects of personalized medicine, whether it is nutrition, exercise, pharmacotherapy, or even surgical procedures.”
Blüher received honoraria for lectures and/or served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
“Obesity only recently caught the public’s attention as a disease,” Matthias Blüher, MD, professor of medicine at the Leipzig University and director of the Helmholtz Institute for Metabolism, Obesity and Vascular Research, Leipzig, Germany, told attendees in a thought-provoking presentation at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.
Even though the attitudes around how obesity is perceived may be relatively new, Blüher believes they are nonetheless significant. As a sign of how the cultural headwinds have shifted, he noted the 2022 film The Whale, which focuses on a character struggling with obesity. As Blüher pointed out, not only did the film’s star, Brendan Fraser, receive an Academy Award for his portrayal but he also theorized that the majority of celebrities in the audience were likely taking new weight loss medications.
“I strongly believe that in the future, obesity treatment will carry less stigma. It will be considered not as a cosmetic problem, but as a progressive disease.”
He sees several changes in the management of obesity likely to occur on the near horizon, beginning with when interventions directed at treating it will begin.
Obesity treatment should start at a young age, he said, because if you have overweight at ages 3-6 years, the likelihood of becoming an adult with obesity is approximately 90%. “Looking ahead, shouldn’t we put more emphasis on this age group?”
Furthermore, he hopes that clinical trials will move beyond body weight and body mass index (BMI) as their main outcome parameters. Instead, “we should talk about fat distribution, fat or adipose tissue function, muscle loss, body composition, and severity of disease.”
Blüher pointed to the recently published framework for the diagnosis, staging, and management of obesity in adults put forward by the European Association for the Study of Obesity. It states that obesity should be staged not based on BMI or body weight alone but also on an individual›s medical, functional, and psychological (eg, mental health and eating behavior) status.
“The causes of obesity are too complex to be individually targeted,” he continued, unlike examples such as hypercholesterolemia or smoking cessation, where clinicians may have one target to address.
“But overeating, slow metabolism, and low physical activity involve socio-cultural factors, global food marketing, and many other factors. Therefore, clinicians should be setting health targets, such as improving sleep apnea and improving physical functioning, rather than a kilogram number.”
Three Pillars of Treatment
Right now, clinicians have three pillars of treatments available, Blüher said. The first is behavioral intervention, including strategies such as counseling, diet, exercise, self-monitoring, stress management, and sleep management.
“We know that these behavioral aspects typically lack adherence and effect size, but they’re important, and for a certain group of people, they may be the best and safest treatment.”
The second pillar is pharmacotherapy, and the third is surgery.
Each pillar poses questions for future research, he explained.
“First, do we really need more evidence that behavioral interventions typically fail in the long run and are prone to rebound of body weight and health issues? No. Or which diet is best? We have hundreds of diet interventions, all of which basically show very similar outcomes. They lead to an average weight loss of 3% to 5% and do improve health conditions associated with obesity.”
When it comes to pharmacotherapies, Blüher does believe clinicians need more options.
Depending on affordability and access, glucagon-like peptide 1 (GLP-1) semaglutide will likely become the first-line therapy for most people living with obesity who want to take medications, he suggested. The dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide will be reserved for those with more severe conditions.
“But this is not the end of the story,” he said. “The pipelines for obesity pharmacotherapies are full, and they have different categories. We are optimistic that we will have more therapies not only for type 2 diabetes (T2D) but also for obesity. Combinations such as CagriSema (cagrilintide + semaglutide, currently indicated for T2D) may outperform the monotherapies. We have to see if they’re as safe, and we have to wait for phase 3 trials and long-term outcomes.”
“The field is open for many combinations, ideas and interactions among the incretin-based signaling systems, but personally, I think that the triple agonists have a very bright future,” Blüher said.
For example, retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors, showed promise in a phase 2 trial. Although that was not a comparative study, “the average changes in body weight suggest that in a dose-dependent manner, you can expect even more weight loss than with tirzepatide.”
Treating the Causes
The future of obesity therapy might also be directed at the originating factors that cause it, Blüher suggested, adding that “treating the causes is a dream of mine.”
One example of treating the cause is leptin therapy, as shown in a 1999 study of recombinant leptin in a child with congenital leptin deficiency. A more recent example is setmelanotide treatment for proopiomelanocortin deficiency.
“We are at the beginning for these causative treatments of obesity, and I hope that the future will hold much more of these insights and targets, as in cancer therapy.”
“Finally,” he said, “We eat with our brain. And so in the future, we also will be better able to use our knowledge about the complex neural circuits that are obesogenic, and how to target them. In doing so, we can learn from surgeons because obesity surgery is very effective in changing the anatomy, and we also observe hormonal changes. We see that ghrelin, GLP-1, peptide YY, and many others are affected when the anatomy changes. Why can’t we use that knowledge to design drugs that resemble or mimic the effect size of bariatric surgery?”
And that goes to the third pillar of treatment and the question of whether the new weight loss drugs may replace surgery, which also was the topic of another EASD session.
Blüher doesn’t see that happening for at least a decade, given that there is still an effect-size gap between tirzepatide and surgery, especially for individuals with T2D. In addition, he noted, there will still be nonresponders to drugs, and clinicians are not treating to target yet. Looking ahead, he foresees a combination of surgery and multi-receptor agonists.
“I believe that obesity won’t be cured in the future, but we will have increasingly better lifelong management with a multidisciplinary approach, although behavioral interventions still will not be as successful as pharmacotherapy and bariatric surgery,” he concluded.
Q&A
During the question-and-answer session following his lecture, several attendees asked Blüher for his thoughts around other emerging areas in this field. One wanted to know whether microbiome changes might be a future target for obesity treatment.
“So far, we don’t really understand which bacteria, which composition, at which age, and at which part of the intestine need to be targeted,” Blüher responded. “Before we know that mechanistically, I think it would be difficult, but it could be an avenue to go for, though I’m a little less optimistic about it compared to other approaches.”
Given that obesity is not one disease, are there cluster subtypes, as for T2D — eg, the hungry brain, the hungry gut, low metabolism — that might benefit from individualized treatment, another attendee asked.
“We do try to subcluster people living with obesity,” Blüher said. “We did that based on adipose tissue expression signatures, and indeed there is large heterogeneity. But we are far from addressing the root causes and all subtypes of the disease, and that would be a requirement before we could personalize treatment in that way.”
Next, an attendee asked what is responsible for the differential weight loss in people with diabetes and people without? Blüher responded that although he doesn’t have the answer, he does have hypotheses.
“One could be that the disease process — eg, deterioration of beta cell function, of the balance of hormones such as insulin and leptin, of inflammatory parameters, of insulin resistance — is much more advanced in diseases such as T2D and sleep apnea. Maybe it then takes more to address comorbid conditions such as inflammation and insulin resistance. Therefore, combining current therapies with insulin sensitizers, for example, could produce better results.”
What about using continuous glucose monitoring to help people stick to their diet?
“That’s an important question that speaks to personalized treatment,” he said. “It applies not only to continuous glucose monitoring but also to nutrition and other modes of self-monitoring, which seem to be among the most successful tools for long-term weight maintenance.”
Blüher finished by saying, “As we look into the future, I hope that there will be better approaches for all aspects of personalized medicine, whether it is nutrition, exercise, pharmacotherapy, or even surgical procedures.”
Blüher received honoraria for lectures and/or served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
“Obesity only recently caught the public’s attention as a disease,” Matthias Blüher, MD, professor of medicine at the Leipzig University and director of the Helmholtz Institute for Metabolism, Obesity and Vascular Research, Leipzig, Germany, told attendees in a thought-provoking presentation at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.
Even though the attitudes around how obesity is perceived may be relatively new, Blüher believes they are nonetheless significant. As a sign of how the cultural headwinds have shifted, he noted the 2022 film The Whale, which focuses on a character struggling with obesity. As Blüher pointed out, not only did the film’s star, Brendan Fraser, receive an Academy Award for his portrayal but he also theorized that the majority of celebrities in the audience were likely taking new weight loss medications.
“I strongly believe that in the future, obesity treatment will carry less stigma. It will be considered not as a cosmetic problem, but as a progressive disease.”
He sees several changes in the management of obesity likely to occur on the near horizon, beginning with when interventions directed at treating it will begin.
Obesity treatment should start at a young age, he said, because if you have overweight at ages 3-6 years, the likelihood of becoming an adult with obesity is approximately 90%. “Looking ahead, shouldn’t we put more emphasis on this age group?”
Furthermore, he hopes that clinical trials will move beyond body weight and body mass index (BMI) as their main outcome parameters. Instead, “we should talk about fat distribution, fat or adipose tissue function, muscle loss, body composition, and severity of disease.”
Blüher pointed to the recently published framework for the diagnosis, staging, and management of obesity in adults put forward by the European Association for the Study of Obesity. It states that obesity should be staged not based on BMI or body weight alone but also on an individual›s medical, functional, and psychological (eg, mental health and eating behavior) status.
“The causes of obesity are too complex to be individually targeted,” he continued, unlike examples such as hypercholesterolemia or smoking cessation, where clinicians may have one target to address.
“But overeating, slow metabolism, and low physical activity involve socio-cultural factors, global food marketing, and many other factors. Therefore, clinicians should be setting health targets, such as improving sleep apnea and improving physical functioning, rather than a kilogram number.”
Three Pillars of Treatment
Right now, clinicians have three pillars of treatments available, Blüher said. The first is behavioral intervention, including strategies such as counseling, diet, exercise, self-monitoring, stress management, and sleep management.
“We know that these behavioral aspects typically lack adherence and effect size, but they’re important, and for a certain group of people, they may be the best and safest treatment.”
The second pillar is pharmacotherapy, and the third is surgery.
Each pillar poses questions for future research, he explained.
“First, do we really need more evidence that behavioral interventions typically fail in the long run and are prone to rebound of body weight and health issues? No. Or which diet is best? We have hundreds of diet interventions, all of which basically show very similar outcomes. They lead to an average weight loss of 3% to 5% and do improve health conditions associated with obesity.”
When it comes to pharmacotherapies, Blüher does believe clinicians need more options.
Depending on affordability and access, glucagon-like peptide 1 (GLP-1) semaglutide will likely become the first-line therapy for most people living with obesity who want to take medications, he suggested. The dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide will be reserved for those with more severe conditions.
“But this is not the end of the story,” he said. “The pipelines for obesity pharmacotherapies are full, and they have different categories. We are optimistic that we will have more therapies not only for type 2 diabetes (T2D) but also for obesity. Combinations such as CagriSema (cagrilintide + semaglutide, currently indicated for T2D) may outperform the monotherapies. We have to see if they’re as safe, and we have to wait for phase 3 trials and long-term outcomes.”
“The field is open for many combinations, ideas and interactions among the incretin-based signaling systems, but personally, I think that the triple agonists have a very bright future,” Blüher said.
For example, retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors, showed promise in a phase 2 trial. Although that was not a comparative study, “the average changes in body weight suggest that in a dose-dependent manner, you can expect even more weight loss than with tirzepatide.”
Treating the Causes
The future of obesity therapy might also be directed at the originating factors that cause it, Blüher suggested, adding that “treating the causes is a dream of mine.”
One example of treating the cause is leptin therapy, as shown in a 1999 study of recombinant leptin in a child with congenital leptin deficiency. A more recent example is setmelanotide treatment for proopiomelanocortin deficiency.
“We are at the beginning for these causative treatments of obesity, and I hope that the future will hold much more of these insights and targets, as in cancer therapy.”
“Finally,” he said, “We eat with our brain. And so in the future, we also will be better able to use our knowledge about the complex neural circuits that are obesogenic, and how to target them. In doing so, we can learn from surgeons because obesity surgery is very effective in changing the anatomy, and we also observe hormonal changes. We see that ghrelin, GLP-1, peptide YY, and many others are affected when the anatomy changes. Why can’t we use that knowledge to design drugs that resemble or mimic the effect size of bariatric surgery?”
And that goes to the third pillar of treatment and the question of whether the new weight loss drugs may replace surgery, which also was the topic of another EASD session.
Blüher doesn’t see that happening for at least a decade, given that there is still an effect-size gap between tirzepatide and surgery, especially for individuals with T2D. In addition, he noted, there will still be nonresponders to drugs, and clinicians are not treating to target yet. Looking ahead, he foresees a combination of surgery and multi-receptor agonists.
“I believe that obesity won’t be cured in the future, but we will have increasingly better lifelong management with a multidisciplinary approach, although behavioral interventions still will not be as successful as pharmacotherapy and bariatric surgery,” he concluded.
Q&A
During the question-and-answer session following his lecture, several attendees asked Blüher for his thoughts around other emerging areas in this field. One wanted to know whether microbiome changes might be a future target for obesity treatment.
“So far, we don’t really understand which bacteria, which composition, at which age, and at which part of the intestine need to be targeted,” Blüher responded. “Before we know that mechanistically, I think it would be difficult, but it could be an avenue to go for, though I’m a little less optimistic about it compared to other approaches.”
Given that obesity is not one disease, are there cluster subtypes, as for T2D — eg, the hungry brain, the hungry gut, low metabolism — that might benefit from individualized treatment, another attendee asked.
“We do try to subcluster people living with obesity,” Blüher said. “We did that based on adipose tissue expression signatures, and indeed there is large heterogeneity. But we are far from addressing the root causes and all subtypes of the disease, and that would be a requirement before we could personalize treatment in that way.”
Next, an attendee asked what is responsible for the differential weight loss in people with diabetes and people without? Blüher responded that although he doesn’t have the answer, he does have hypotheses.
“One could be that the disease process — eg, deterioration of beta cell function, of the balance of hormones such as insulin and leptin, of inflammatory parameters, of insulin resistance — is much more advanced in diseases such as T2D and sleep apnea. Maybe it then takes more to address comorbid conditions such as inflammation and insulin resistance. Therefore, combining current therapies with insulin sensitizers, for example, could produce better results.”
What about using continuous glucose monitoring to help people stick to their diet?
“That’s an important question that speaks to personalized treatment,” he said. “It applies not only to continuous glucose monitoring but also to nutrition and other modes of self-monitoring, which seem to be among the most successful tools for long-term weight maintenance.”
Blüher finished by saying, “As we look into the future, I hope that there will be better approaches for all aspects of personalized medicine, whether it is nutrition, exercise, pharmacotherapy, or even surgical procedures.”
Blüher received honoraria for lectures and/or served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM EASD 2024
Time to Stop Saying Thyroid Cancer Is a ‘Good’ Cancer
Papillary thyroid cancer is widely known as the “good cancer.” This term has been around for years and is used ubiquitously. Some think it’s “appropriate” because the cancer is highly treatable and has good survival rates. Yet, recent research, provider experiences, and patient feedback suggest the term should no longer be used.
Papillary is the most common type of thyroid cancer, comprising about 70%-80% of all thyroid cancers. It tends to grow slowly and “has a generally excellent outlook, even if there is spread to the lymph nodes,” according to the American Thyroid Association.
This “excellent outlook” can prompt a physician to call it a “good” cancer.
“There is often a perception that a patient is diagnosed, treated, and then once treatment is complete, gets to go back to their ‘normal’ lives,” said Fiona Schulte, PhD, RPsych, of the University of Calgary, Alberta, Canada.
“The surgery and other treatments thyroid patients may require are not benign and leave patients with many long-term challenging consequences,” she said in an interview. “For many, treatment is just the beginning of a long journey of dealing with multiple late effects.”
Misguided ‘Support’
“I do believe the doctor’s intention is to bring comfort to the patient by saying they have a very curable disease,” Miranda Fidler-Benaoudia, MD, of the University of Calgary, said in an interview. Fidler-Benaoudia is the principal author of a recent survey/interview study of early-onset thyroid cancer survivors, titled “No such thing as a good cancer.” Despite the doctor’s intention, her team found that “for the majority of individuals interviewed, the response was actually quite negative.”
“Specifically,” she said, “thyroid cancer patients felt that the use of the term ‘good cancer’ minimized their diagnosis and experience, often making them feel like their struggles with the diagnosis and its treatment were not justified. While they were indeed cancer patients, they did not feel they could claim to be one because their prognosis was very positive or they didn’t have more intensive therapies like radiotherapy or chemotherapy.”
These feelings were echoed in a recent Moffitt Center article. When Emma Stevens learned she had thyroid cancer at age 19, she said she heard the same statements repeatedly, including: “At least it’s only thyroid cancer.” “It’s the good cancer, and easy to deal with.”
“These are such weird things to say to me,” said Stevens, now 26. “I know they didn’t have any ill will and they couldn’t see how such statements could be upsetting. It’s been my goal to shed some light on how what they see as encouraging thoughts can upset someone like me.”
In an article on the appropriateness of the term “good cancer,” Reese W. Randle, MD, now at Wake Forest University School of Medicine, Winston-Salem, North Carolina, and colleagues wrote, “Patients with papillary thyroid cancer commonly confront the perception that their malignancy is ‘good,’ but the favorable prognosis and treatability of the disease do not comprehensively represent their cancer fight.”
“The ‘good cancer’ perception is at the root of many mixed and confusing emotions,” they continued. “Clinicians emphasize optimistic outcomes, hoping to comfort, but they might inadvertently invalidate the impact thyroid cancer has on patients’ lives.”
Life-Altering
“Having a diagnosis of thyroid cancer, even with usually a very good prognosis, can be life-altering, said Caitlin P. McMullen, MD, a head and neck cancer specialist at Moffitt Cancer Center, Tampa, Florida.
Most papillary thyroid cancers are cured with surgery alone, sometimes followed by radioactive iodine, she said in an interview. “The surgery involves removing half (lobectomy), or sometimes all (total thyroidectomy), of the thyroid gland.” Patients with lymph node involvement have a longer surgery that includes lymph node removal.
Many patients must also remain on medication permanently to replace their thyroid hormone, she continued. And, after treatment is complete, “patients require regular follow up with bloodwork and imaging for many years to ensure the cancer does not return.”
“Repeated visits, medications, and testing can also result in financial toxicities and repeated disruptions for patients,” she added. “These downstream effects of a thyroid cancer diagnosis can significantly alter a patient’s life.”
Kaniksha Desai, MD, Endocrinology Quality Director at Stanford University School of Medicine, Palo Alto, California, said in an interview that thyroid cancer treatments carry some risks that shouldn’t be overlooked and may affect recovery for years. These include:
- Recurrent laryngeal nerve damage: Thyroid surgery can lead to vocal cord paralysis, affecting speech and swallowing.
- Hypoparathyroidism: Postsurgical damage to the parathyroid glands can cause long-term calcium regulation problems resulting in pain and emergency department visits as well as lifelong supplementation with calcium and vitamin D.
- Radioactive iodine (RAI) treatment: RAI can have side effects such as dry mouth, tear duct obstruction, salivary gland dysfunction, and an increased risk of secondary cancers.
- Psychosocial Impact: Being told they have cancer can create significant psychological distress for patients, including fear of recurrence, body image concerns, and anxiety, all of which persist even with a “good prognosis.”
Fidler-Benaoudia’s studies focused specifically on the psychosocial impact on younger patients. “Facing a cancer diagnosis at a young age really forces the person to hit the ‘pause button’ – they may need to take a break from school or work, and it may impact their relationships with their family and friends.”
“Even if their cancer has a very high survival rate, when a young person receives a cancer diagnosis they are often facing their own immortality for the first time, which can be very distressing,” she said. Many of her study participants also struggled to maintain appropriate thyroid hormone levels with medication, which left them feeling tired, losing hair or gaining weight. The surgery itself “can leave a substantial scar on the throat that is visible unless purposefully covered with clothing or accessories,” she noted. “We found that this scar impacted quite a few survivors’ body image.”
Awareness, Education
Two recent studies pointed to the need for clinicians to be aware of their patients’ reactions to a thyroid diagnosis. Susan C. Pitt, MD, associate professor of surgery and director of the endocrine surgery health services research program at the University of Michigan, Ann Arbor, and colleagues reviewed the literature on patient perception of receiving a thyroid diagnosis and found, “Fear and worry about cancer in general and the possibility for recurrence contribute to lasting psychological distress and decreased quality of life. Patients’ perceptions of their diagnosis and resulting emotional reactions influence treatment decision making and have the potential to contribute to decisions that may over-treat a low-risk thyroid cancer.”
In another recent study, Pitt and colleagues assessed fear of thyroid cancer in the general US population and found that close to half of 1136 respondents to an online survey had high levels of thyroid cancer-specific fear, particularly women and those under age 40. “Because disease-specific fear is associated with overtreatment, targeted education about the seriousness, incidence, and risk factors for developing thyroid cancer may decrease public fear and possibly overtreatment related to ‘scared decision-making,’” the authors concluded.
McMullen added, “Taking the time to educate the patient on the diagnosis, prognosis, and treatments can provide reassurance without being dismissive. Most patients are very receptive and understanding once things are explained thoroughly and their questions are answered. We find that factual information can be even more reassuring for patients than saying, ‘This is a good cancer.’”
Desai advised, “Clinicians should acknowledge the spectrum of experiences patients may have.” They should provide empathy and reassurance as well as personalized discussions regarding prognosis and treatment options. In addition, “they should focus on survivorship care by addressing both the long-term and short-term effects on health and lifestyle that can occur post treatment,” as well as the possible need for mental health support.
“I heard many times in residency that, ‘if you had to have cancer, have thyroid cancer,’ ” Malini Gupta, MD, director of G2Endo Endocrinology & Metabolism, Memphis, Tennessee, and vice chair of the American Association of Clinical Endocrinology’s Disease State Networks, said in an interview.
“One should not want any cancer,” she said. “There are some very aggressive tumor markers in differentiated thyroid cancer that can have a worse prognosis. There are many aspects of thyroid cancer treatment that cause anxiety and a stress burden. Recovery varies from person to person.”
“There needs to be education across all sectors of healthcare, particularly in primary care,” she added. “I personally have medullary thyroid cancer that I found myself while fixing my ultrasound. There are many aspects to survivorship.”
Fidler-Benaoudia, Schulte, McMullen, and Desai declared no competing interests. Gupta is on the speaker bureau for Amgen (Tepezza) and IBSA (Tirosint) and is a creative consultant for AbbVie.
A version of this article first appeared on Medscape.com.
Papillary thyroid cancer is widely known as the “good cancer.” This term has been around for years and is used ubiquitously. Some think it’s “appropriate” because the cancer is highly treatable and has good survival rates. Yet, recent research, provider experiences, and patient feedback suggest the term should no longer be used.
Papillary is the most common type of thyroid cancer, comprising about 70%-80% of all thyroid cancers. It tends to grow slowly and “has a generally excellent outlook, even if there is spread to the lymph nodes,” according to the American Thyroid Association.
This “excellent outlook” can prompt a physician to call it a “good” cancer.
“There is often a perception that a patient is diagnosed, treated, and then once treatment is complete, gets to go back to their ‘normal’ lives,” said Fiona Schulte, PhD, RPsych, of the University of Calgary, Alberta, Canada.
“The surgery and other treatments thyroid patients may require are not benign and leave patients with many long-term challenging consequences,” she said in an interview. “For many, treatment is just the beginning of a long journey of dealing with multiple late effects.”
Misguided ‘Support’
“I do believe the doctor’s intention is to bring comfort to the patient by saying they have a very curable disease,” Miranda Fidler-Benaoudia, MD, of the University of Calgary, said in an interview. Fidler-Benaoudia is the principal author of a recent survey/interview study of early-onset thyroid cancer survivors, titled “No such thing as a good cancer.” Despite the doctor’s intention, her team found that “for the majority of individuals interviewed, the response was actually quite negative.”
“Specifically,” she said, “thyroid cancer patients felt that the use of the term ‘good cancer’ minimized their diagnosis and experience, often making them feel like their struggles with the diagnosis and its treatment were not justified. While they were indeed cancer patients, they did not feel they could claim to be one because their prognosis was very positive or they didn’t have more intensive therapies like radiotherapy or chemotherapy.”
These feelings were echoed in a recent Moffitt Center article. When Emma Stevens learned she had thyroid cancer at age 19, she said she heard the same statements repeatedly, including: “At least it’s only thyroid cancer.” “It’s the good cancer, and easy to deal with.”
“These are such weird things to say to me,” said Stevens, now 26. “I know they didn’t have any ill will and they couldn’t see how such statements could be upsetting. It’s been my goal to shed some light on how what they see as encouraging thoughts can upset someone like me.”
In an article on the appropriateness of the term “good cancer,” Reese W. Randle, MD, now at Wake Forest University School of Medicine, Winston-Salem, North Carolina, and colleagues wrote, “Patients with papillary thyroid cancer commonly confront the perception that their malignancy is ‘good,’ but the favorable prognosis and treatability of the disease do not comprehensively represent their cancer fight.”
“The ‘good cancer’ perception is at the root of many mixed and confusing emotions,” they continued. “Clinicians emphasize optimistic outcomes, hoping to comfort, but they might inadvertently invalidate the impact thyroid cancer has on patients’ lives.”
Life-Altering
“Having a diagnosis of thyroid cancer, even with usually a very good prognosis, can be life-altering, said Caitlin P. McMullen, MD, a head and neck cancer specialist at Moffitt Cancer Center, Tampa, Florida.
Most papillary thyroid cancers are cured with surgery alone, sometimes followed by radioactive iodine, she said in an interview. “The surgery involves removing half (lobectomy), or sometimes all (total thyroidectomy), of the thyroid gland.” Patients with lymph node involvement have a longer surgery that includes lymph node removal.
Many patients must also remain on medication permanently to replace their thyroid hormone, she continued. And, after treatment is complete, “patients require regular follow up with bloodwork and imaging for many years to ensure the cancer does not return.”
“Repeated visits, medications, and testing can also result in financial toxicities and repeated disruptions for patients,” she added. “These downstream effects of a thyroid cancer diagnosis can significantly alter a patient’s life.”
Kaniksha Desai, MD, Endocrinology Quality Director at Stanford University School of Medicine, Palo Alto, California, said in an interview that thyroid cancer treatments carry some risks that shouldn’t be overlooked and may affect recovery for years. These include:
- Recurrent laryngeal nerve damage: Thyroid surgery can lead to vocal cord paralysis, affecting speech and swallowing.
- Hypoparathyroidism: Postsurgical damage to the parathyroid glands can cause long-term calcium regulation problems resulting in pain and emergency department visits as well as lifelong supplementation with calcium and vitamin D.
- Radioactive iodine (RAI) treatment: RAI can have side effects such as dry mouth, tear duct obstruction, salivary gland dysfunction, and an increased risk of secondary cancers.
- Psychosocial Impact: Being told they have cancer can create significant psychological distress for patients, including fear of recurrence, body image concerns, and anxiety, all of which persist even with a “good prognosis.”
Fidler-Benaoudia’s studies focused specifically on the psychosocial impact on younger patients. “Facing a cancer diagnosis at a young age really forces the person to hit the ‘pause button’ – they may need to take a break from school or work, and it may impact their relationships with their family and friends.”
“Even if their cancer has a very high survival rate, when a young person receives a cancer diagnosis they are often facing their own immortality for the first time, which can be very distressing,” she said. Many of her study participants also struggled to maintain appropriate thyroid hormone levels with medication, which left them feeling tired, losing hair or gaining weight. The surgery itself “can leave a substantial scar on the throat that is visible unless purposefully covered with clothing or accessories,” she noted. “We found that this scar impacted quite a few survivors’ body image.”
Awareness, Education
Two recent studies pointed to the need for clinicians to be aware of their patients’ reactions to a thyroid diagnosis. Susan C. Pitt, MD, associate professor of surgery and director of the endocrine surgery health services research program at the University of Michigan, Ann Arbor, and colleagues reviewed the literature on patient perception of receiving a thyroid diagnosis and found, “Fear and worry about cancer in general and the possibility for recurrence contribute to lasting psychological distress and decreased quality of life. Patients’ perceptions of their diagnosis and resulting emotional reactions influence treatment decision making and have the potential to contribute to decisions that may over-treat a low-risk thyroid cancer.”
In another recent study, Pitt and colleagues assessed fear of thyroid cancer in the general US population and found that close to half of 1136 respondents to an online survey had high levels of thyroid cancer-specific fear, particularly women and those under age 40. “Because disease-specific fear is associated with overtreatment, targeted education about the seriousness, incidence, and risk factors for developing thyroid cancer may decrease public fear and possibly overtreatment related to ‘scared decision-making,’” the authors concluded.
McMullen added, “Taking the time to educate the patient on the diagnosis, prognosis, and treatments can provide reassurance without being dismissive. Most patients are very receptive and understanding once things are explained thoroughly and their questions are answered. We find that factual information can be even more reassuring for patients than saying, ‘This is a good cancer.’”
Desai advised, “Clinicians should acknowledge the spectrum of experiences patients may have.” They should provide empathy and reassurance as well as personalized discussions regarding prognosis and treatment options. In addition, “they should focus on survivorship care by addressing both the long-term and short-term effects on health and lifestyle that can occur post treatment,” as well as the possible need for mental health support.
“I heard many times in residency that, ‘if you had to have cancer, have thyroid cancer,’ ” Malini Gupta, MD, director of G2Endo Endocrinology & Metabolism, Memphis, Tennessee, and vice chair of the American Association of Clinical Endocrinology’s Disease State Networks, said in an interview.
“One should not want any cancer,” she said. “There are some very aggressive tumor markers in differentiated thyroid cancer that can have a worse prognosis. There are many aspects of thyroid cancer treatment that cause anxiety and a stress burden. Recovery varies from person to person.”
“There needs to be education across all sectors of healthcare, particularly in primary care,” she added. “I personally have medullary thyroid cancer that I found myself while fixing my ultrasound. There are many aspects to survivorship.”
Fidler-Benaoudia, Schulte, McMullen, and Desai declared no competing interests. Gupta is on the speaker bureau for Amgen (Tepezza) and IBSA (Tirosint) and is a creative consultant for AbbVie.
A version of this article first appeared on Medscape.com.
Papillary thyroid cancer is widely known as the “good cancer.” This term has been around for years and is used ubiquitously. Some think it’s “appropriate” because the cancer is highly treatable and has good survival rates. Yet, recent research, provider experiences, and patient feedback suggest the term should no longer be used.
Papillary is the most common type of thyroid cancer, comprising about 70%-80% of all thyroid cancers. It tends to grow slowly and “has a generally excellent outlook, even if there is spread to the lymph nodes,” according to the American Thyroid Association.
This “excellent outlook” can prompt a physician to call it a “good” cancer.
“There is often a perception that a patient is diagnosed, treated, and then once treatment is complete, gets to go back to their ‘normal’ lives,” said Fiona Schulte, PhD, RPsych, of the University of Calgary, Alberta, Canada.
“The surgery and other treatments thyroid patients may require are not benign and leave patients with many long-term challenging consequences,” she said in an interview. “For many, treatment is just the beginning of a long journey of dealing with multiple late effects.”
Misguided ‘Support’
“I do believe the doctor’s intention is to bring comfort to the patient by saying they have a very curable disease,” Miranda Fidler-Benaoudia, MD, of the University of Calgary, said in an interview. Fidler-Benaoudia is the principal author of a recent survey/interview study of early-onset thyroid cancer survivors, titled “No such thing as a good cancer.” Despite the doctor’s intention, her team found that “for the majority of individuals interviewed, the response was actually quite negative.”
“Specifically,” she said, “thyroid cancer patients felt that the use of the term ‘good cancer’ minimized their diagnosis and experience, often making them feel like their struggles with the diagnosis and its treatment were not justified. While they were indeed cancer patients, they did not feel they could claim to be one because their prognosis was very positive or they didn’t have more intensive therapies like radiotherapy or chemotherapy.”
These feelings were echoed in a recent Moffitt Center article. When Emma Stevens learned she had thyroid cancer at age 19, she said she heard the same statements repeatedly, including: “At least it’s only thyroid cancer.” “It’s the good cancer, and easy to deal with.”
“These are such weird things to say to me,” said Stevens, now 26. “I know they didn’t have any ill will and they couldn’t see how such statements could be upsetting. It’s been my goal to shed some light on how what they see as encouraging thoughts can upset someone like me.”
In an article on the appropriateness of the term “good cancer,” Reese W. Randle, MD, now at Wake Forest University School of Medicine, Winston-Salem, North Carolina, and colleagues wrote, “Patients with papillary thyroid cancer commonly confront the perception that their malignancy is ‘good,’ but the favorable prognosis and treatability of the disease do not comprehensively represent their cancer fight.”
“The ‘good cancer’ perception is at the root of many mixed and confusing emotions,” they continued. “Clinicians emphasize optimistic outcomes, hoping to comfort, but they might inadvertently invalidate the impact thyroid cancer has on patients’ lives.”
Life-Altering
“Having a diagnosis of thyroid cancer, even with usually a very good prognosis, can be life-altering, said Caitlin P. McMullen, MD, a head and neck cancer specialist at Moffitt Cancer Center, Tampa, Florida.
Most papillary thyroid cancers are cured with surgery alone, sometimes followed by radioactive iodine, she said in an interview. “The surgery involves removing half (lobectomy), or sometimes all (total thyroidectomy), of the thyroid gland.” Patients with lymph node involvement have a longer surgery that includes lymph node removal.
Many patients must also remain on medication permanently to replace their thyroid hormone, she continued. And, after treatment is complete, “patients require regular follow up with bloodwork and imaging for many years to ensure the cancer does not return.”
“Repeated visits, medications, and testing can also result in financial toxicities and repeated disruptions for patients,” she added. “These downstream effects of a thyroid cancer diagnosis can significantly alter a patient’s life.”
Kaniksha Desai, MD, Endocrinology Quality Director at Stanford University School of Medicine, Palo Alto, California, said in an interview that thyroid cancer treatments carry some risks that shouldn’t be overlooked and may affect recovery for years. These include:
- Recurrent laryngeal nerve damage: Thyroid surgery can lead to vocal cord paralysis, affecting speech and swallowing.
- Hypoparathyroidism: Postsurgical damage to the parathyroid glands can cause long-term calcium regulation problems resulting in pain and emergency department visits as well as lifelong supplementation with calcium and vitamin D.
- Radioactive iodine (RAI) treatment: RAI can have side effects such as dry mouth, tear duct obstruction, salivary gland dysfunction, and an increased risk of secondary cancers.
- Psychosocial Impact: Being told they have cancer can create significant psychological distress for patients, including fear of recurrence, body image concerns, and anxiety, all of which persist even with a “good prognosis.”
Fidler-Benaoudia’s studies focused specifically on the psychosocial impact on younger patients. “Facing a cancer diagnosis at a young age really forces the person to hit the ‘pause button’ – they may need to take a break from school or work, and it may impact their relationships with their family and friends.”
“Even if their cancer has a very high survival rate, when a young person receives a cancer diagnosis they are often facing their own immortality for the first time, which can be very distressing,” she said. Many of her study participants also struggled to maintain appropriate thyroid hormone levels with medication, which left them feeling tired, losing hair or gaining weight. The surgery itself “can leave a substantial scar on the throat that is visible unless purposefully covered with clothing or accessories,” she noted. “We found that this scar impacted quite a few survivors’ body image.”
Awareness, Education
Two recent studies pointed to the need for clinicians to be aware of their patients’ reactions to a thyroid diagnosis. Susan C. Pitt, MD, associate professor of surgery and director of the endocrine surgery health services research program at the University of Michigan, Ann Arbor, and colleagues reviewed the literature on patient perception of receiving a thyroid diagnosis and found, “Fear and worry about cancer in general and the possibility for recurrence contribute to lasting psychological distress and decreased quality of life. Patients’ perceptions of their diagnosis and resulting emotional reactions influence treatment decision making and have the potential to contribute to decisions that may over-treat a low-risk thyroid cancer.”
In another recent study, Pitt and colleagues assessed fear of thyroid cancer in the general US population and found that close to half of 1136 respondents to an online survey had high levels of thyroid cancer-specific fear, particularly women and those under age 40. “Because disease-specific fear is associated with overtreatment, targeted education about the seriousness, incidence, and risk factors for developing thyroid cancer may decrease public fear and possibly overtreatment related to ‘scared decision-making,’” the authors concluded.
McMullen added, “Taking the time to educate the patient on the diagnosis, prognosis, and treatments can provide reassurance without being dismissive. Most patients are very receptive and understanding once things are explained thoroughly and their questions are answered. We find that factual information can be even more reassuring for patients than saying, ‘This is a good cancer.’”
Desai advised, “Clinicians should acknowledge the spectrum of experiences patients may have.” They should provide empathy and reassurance as well as personalized discussions regarding prognosis and treatment options. In addition, “they should focus on survivorship care by addressing both the long-term and short-term effects on health and lifestyle that can occur post treatment,” as well as the possible need for mental health support.
“I heard many times in residency that, ‘if you had to have cancer, have thyroid cancer,’ ” Malini Gupta, MD, director of G2Endo Endocrinology & Metabolism, Memphis, Tennessee, and vice chair of the American Association of Clinical Endocrinology’s Disease State Networks, said in an interview.
“One should not want any cancer,” she said. “There are some very aggressive tumor markers in differentiated thyroid cancer that can have a worse prognosis. There are many aspects of thyroid cancer treatment that cause anxiety and a stress burden. Recovery varies from person to person.”
“There needs to be education across all sectors of healthcare, particularly in primary care,” she added. “I personally have medullary thyroid cancer that I found myself while fixing my ultrasound. There are many aspects to survivorship.”
Fidler-Benaoudia, Schulte, McMullen, and Desai declared no competing interests. Gupta is on the speaker bureau for Amgen (Tepezza) and IBSA (Tirosint) and is a creative consultant for AbbVie.
A version of this article first appeared on Medscape.com.
Tirzepatide Shortage Resolved? FDA Says Yes, Compounders No
The agency wrote in a clarification aimed at compounders that Lilly said it can meet the “present and projected national demand” and that compounders are restricted from making the products.
Nevertheless, patients and prescribers may still see “intermittent localized supply disruptions as the products move through the supply chain,” the FDA noted.
The Alliance for Pharmacy Compounding (APC) responded swiftly, alerting its members and the public to the resolved shortage and stating that compounders “must immediately cease preparing and dispensing compounded copies” of the two drugs.
However, APC CEO Scott Brunner added it often takes a long time for FDA-approved versions of the drug to become widely available to wholesalers, hospitals, and clinics. Even after Lilly announced greater availability for the drugs, including in a new vial format for low doses, “for most pharmacies, they’re lucky to get two or three boxes of Zepbound a day from their wholesaler — for a patient waiting list that can number in the hundreds.”
“We have already heard this morning from APC members that they are unable to fill orders for their patients,” he said.
Furthermore, he contended, “I suspect plenty of patients taking compounded tirzepatide are going to be caught flat-footed by this. They are being cut off cold turkey, their prescription no longer fillable. They’ll need to get in to see their provider to get a new prescription, and that will take some time. It’s possible that so many patients presently taking compounded GLP-1s [glucagon-like peptide 1] will be eventually switched to the FDA-approved versions — if they can afford them, of course — that it will push tirzepatide injection back into shortage.”
Commenting on the shortage resolution, endocrinologist Beverly Tchang, MD, DABOM, an assistant professor of clinical medicine at Weill Cornell Medicine in New York City told this news organization, “we are not yet experiencing relief from the shortages, but I hope this resolves at least one barrier to access for our patients.”
“I don’t think it will create confusion,” she said. “Fortunately or unfortunately, patients and clinicians are adept by now with therapeutic transitions because we’ve been forced to do so whenever insurance withdraws coverage or a shortage recurs or a coupon expires. It’s obviously not ideal but patients are motivated and clinicians don’t give up.”
This news organization has previously reported on the impact of the shortages and how endocrinologists and obesity medicine specialists were handling them, in light of concerns about compounding pharmacies that may or may not be well founded.
Dr. Tchang declared that she is an adviser to Novo Nordisk.
A version of this article appeared on Medscape.com.
The agency wrote in a clarification aimed at compounders that Lilly said it can meet the “present and projected national demand” and that compounders are restricted from making the products.
Nevertheless, patients and prescribers may still see “intermittent localized supply disruptions as the products move through the supply chain,” the FDA noted.
The Alliance for Pharmacy Compounding (APC) responded swiftly, alerting its members and the public to the resolved shortage and stating that compounders “must immediately cease preparing and dispensing compounded copies” of the two drugs.
However, APC CEO Scott Brunner added it often takes a long time for FDA-approved versions of the drug to become widely available to wholesalers, hospitals, and clinics. Even after Lilly announced greater availability for the drugs, including in a new vial format for low doses, “for most pharmacies, they’re lucky to get two or three boxes of Zepbound a day from their wholesaler — for a patient waiting list that can number in the hundreds.”
“We have already heard this morning from APC members that they are unable to fill orders for their patients,” he said.
Furthermore, he contended, “I suspect plenty of patients taking compounded tirzepatide are going to be caught flat-footed by this. They are being cut off cold turkey, their prescription no longer fillable. They’ll need to get in to see their provider to get a new prescription, and that will take some time. It’s possible that so many patients presently taking compounded GLP-1s [glucagon-like peptide 1] will be eventually switched to the FDA-approved versions — if they can afford them, of course — that it will push tirzepatide injection back into shortage.”
Commenting on the shortage resolution, endocrinologist Beverly Tchang, MD, DABOM, an assistant professor of clinical medicine at Weill Cornell Medicine in New York City told this news organization, “we are not yet experiencing relief from the shortages, but I hope this resolves at least one barrier to access for our patients.”
“I don’t think it will create confusion,” she said. “Fortunately or unfortunately, patients and clinicians are adept by now with therapeutic transitions because we’ve been forced to do so whenever insurance withdraws coverage or a shortage recurs or a coupon expires. It’s obviously not ideal but patients are motivated and clinicians don’t give up.”
This news organization has previously reported on the impact of the shortages and how endocrinologists and obesity medicine specialists were handling them, in light of concerns about compounding pharmacies that may or may not be well founded.
Dr. Tchang declared that she is an adviser to Novo Nordisk.
A version of this article appeared on Medscape.com.
The agency wrote in a clarification aimed at compounders that Lilly said it can meet the “present and projected national demand” and that compounders are restricted from making the products.
Nevertheless, patients and prescribers may still see “intermittent localized supply disruptions as the products move through the supply chain,” the FDA noted.
The Alliance for Pharmacy Compounding (APC) responded swiftly, alerting its members and the public to the resolved shortage and stating that compounders “must immediately cease preparing and dispensing compounded copies” of the two drugs.
However, APC CEO Scott Brunner added it often takes a long time for FDA-approved versions of the drug to become widely available to wholesalers, hospitals, and clinics. Even after Lilly announced greater availability for the drugs, including in a new vial format for low doses, “for most pharmacies, they’re lucky to get two or three boxes of Zepbound a day from their wholesaler — for a patient waiting list that can number in the hundreds.”
“We have already heard this morning from APC members that they are unable to fill orders for their patients,” he said.
Furthermore, he contended, “I suspect plenty of patients taking compounded tirzepatide are going to be caught flat-footed by this. They are being cut off cold turkey, their prescription no longer fillable. They’ll need to get in to see their provider to get a new prescription, and that will take some time. It’s possible that so many patients presently taking compounded GLP-1s [glucagon-like peptide 1] will be eventually switched to the FDA-approved versions — if they can afford them, of course — that it will push tirzepatide injection back into shortage.”
Commenting on the shortage resolution, endocrinologist Beverly Tchang, MD, DABOM, an assistant professor of clinical medicine at Weill Cornell Medicine in New York City told this news organization, “we are not yet experiencing relief from the shortages, but I hope this resolves at least one barrier to access for our patients.”
“I don’t think it will create confusion,” she said. “Fortunately or unfortunately, patients and clinicians are adept by now with therapeutic transitions because we’ve been forced to do so whenever insurance withdraws coverage or a shortage recurs or a coupon expires. It’s obviously not ideal but patients are motivated and clinicians don’t give up.”
This news organization has previously reported on the impact of the shortages and how endocrinologists and obesity medicine specialists were handling them, in light of concerns about compounding pharmacies that may or may not be well founded.
Dr. Tchang declared that she is an adviser to Novo Nordisk.
A version of this article appeared on Medscape.com.
Cannabis Use Rising in Diabetes: What Do Endos Need to Know?
A recent US prevalence study estimated that 9% adults with diabetes used cannabis in the last month, a 33.7% increase between 2021 and 2022. Nearly half (48.9%) of users were younger than 50 years.
Cannabis use is also increasing sharply among those aged 65 years or older, many of whom have diabetes and other chronic conditions. In this demographic, the perceived risk surrounding regular cannabis use has dropped significantly, even as the data tell another story — that they are particularly at risk from emergency department visits for cannabis poisoning.
As legalization continues and cannabis products proliferate, endocrinologists will likely face more patients of all ages seeking advice about its use. Yet with few evidence-based resources to turn to, endocrinologists advising patients in this area are mostly left fending for themselves.
Evidence ‘Limited’
“The evidence on cannabis is limited mainly because of its scheduling in the United States,” Jay Shubrook, DO, a professor and diabetologist at College of Osteopathic Medicine, Touro University California, in Vallejo, California, told this news organization.
“It was declared to be a schedule I drug in the 1970s, which meant it was ‘dangerous’ and ‘had no medical benefit.’ This made it hard to access and study in human trials.”
That will likely change soon. On May 16, 2024, the US Department of Justice submitted a proposal to move marijuana from a schedule I to a schedule III drug under the Controlled Substances Act, emphasizing its accepted medical use. If approved, the door will open to more investigators seeking to study the effects of cannabis.
Yet, even in Canada, where recreational use has been legal since 2018 and cannabis is sold widely with government support, there are little hard data to guide practice. In 2019, Diabetes Canada issued a position statement on recreational cannabis use in people with type 1 diabetes (T1D) and type 2 diabetes (T2D). It sought to evaluate the effects of cannabis on metabolic factors and diabetes complications, as well as self-management behaviors in those aged 13 years or older.
The authors noted that five of the six studies upon which the statement was based did not consider or report the routes of cannabis administration, which have differing risks. In addition, their recommendations were based on grade D evidence and consensus.
What Patients Are Taking
Cannabis — also known as marijuana, weed, pot, or bud — refers to the dried flowers, leaves, stems, and seeds of the cannabis plant. The plant contains more than 100 compounds, including tetrahydrocannabinol (THC), which is responsible for the euphoric “high,” and other active compounds, including cannabidiol (CBD), which by itself is not mind-altering.
Cannabis can be ingested in several ways. It can be smoked (ie, joints, blunts, pipes, and water pipes), ingested in edible form (mixed or infused into foods), and inhaled using electronic vaporizing devices (ie, e-cigarettes or vape pens).
Compounds in cannabis can also be extracted to make oils and concentrates that can be vaped or inhaled. Smoking oils, concentrates, and extracts from the cannabis plant, known as “dabbing,” are on the rise in the United States.
There are no validated or standard dosage recommendations for cannabis strains and formulations, THC/CBD ratios, or modes of administration. Therefore, the Canadian Pharmacists Association prepared a guide for finding a safe and effective dose for medical purposes. GoodRx, a website with information on prescription drug prices, says that larger doses of THC pose greater risks, noting that the potency of cannabis has increased from 4% in 1995 to about 14% in 2019.
Potential Risks and Benefits: Canadian and US Perspectives
Health and safety risks vary with each of the different ways of using cannabis for individuals with and without diabetes, depending on a host of patient- and product-specific factors.
In a recent article proposing a “THC unit” for Canada’s legal cannabis market, researchers reported that consumers lack familiarity with THC levels, don’t know what constitutes a “low” or “high” THC amount, have trouble dosing, overconsume, and commonly experience adverse health events from cannabis use.
A recent study suggested that most clinicians are similarly uninformed, with “a lack of knowledge of beneficial effects, adverse effects, and of how to advise patients,” even for medical cannabis.
Diabetes Canada takes a stab at summarizing what’s known with respect to cannabis and diabetes, stating that:
“Research on recreational cannabis use suggests it may negatively impact diabetes metabolic factors and self-management behaviors. The safety of recreational cannabis use has not been demonstrated, whereas regular cannabis use is associated with worsening glycemic control, more diabetes-related complications, and poorer self-care behaviors, such as adequate glucose monitoring, adherence to medications, and compliance with dietary and physical activity recommendations for people living with both type 1 and type 2 diabetes.”
The American Diabetes Association’s information on cannabis consists of a patient-oriented article on CBD oil. The article stated:
“There’s a lot of hype surrounding CBD oil and diabetes. There is no noticeable effect on blood glucose (blood sugar) or insulin levels in people with type 2 diabetes. Researchers continue to study the effects of CBD on diabetes in animal studies.”
It concludes that:
“Although many claims continue to be made about CBD oil, there is little evidence of any benefit. It’s certainly not an alternative to traditional diabetes management. The safety of CBD is also unknown — it may have dangerous side effects that we won’t know about unless further research is done.”
A Roundup of Recent Studies
A smattering of recent studies have touched on various aspects of cannabis consumption and diabetes.
Angela Bryan, PhD, professor and co-director of CUChange at the University of Colorado Boulder, has been evaluating cannabis use in young adults (ages 21-40 years) in the SONIC study. Dr. Bryan reported at the American Diabetes Association (ADA) 84th Scientific Sessions that cannabis users were more likely to have a lower body mass index and less likely to develop T2D. Furthermore, chronic cannabis users were less likely to have measures of inflammation and no loss of insulin sensitivity.
Another study by Dr. Bryan’s group found that CBD-dominant forms of cannabis were associated with acute tension reduction, which might lead to longer-term reductions in anxiety. Bryan said the findings could be relevant in the context of diabetes distress.
Similarly positive results were found in a 15-week, double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD spray for neuropathic pain among treatment-resistant patients. The investigators reported that “clinically important improvements” were seen in pain, sleep quality, and subjective impressions of pain. Another small study of inhaled cannabis in treatment-refractory patients found a dose-dependent reduction in diabetic peripheral neuropathy pain.
Findings from a 9-year longitudinal study of approximately 18,000 Swedish men and women suggested no association between cannabis and subsequent T2D development after controlling for age, although these authors also called for longer follow-up and more detailed information about cannabis use to make “more robust” conclusions.
On the other side of the spectrum, a “rapid” review of recreational cannabis use in people with T1D and T2D found that recreational cannabis use may negatively impact diabetes metabolic factors and self-management behaviors and may increase risks for peripheral arterial occlusion, myocardial infarction, and renal disease. However, the authors cautioned that more robust research is needed to confirm the potential impact of cannabis on diabetes.
How to Advise Patients
When Dr. Shubrook was working with patients with diabetes in his family medicine practice in Ohio, cannabis wasn’t legal.
“’Don’t ask, don’t tell’ was the way we handled it then,” he said.
By contrast, in California, where he’s currently located, “it’s pretty well accepted and legal, and patients volunteer information about use, even if it’s recreational,” he said. “Realizing this was something we could talk about was really eye-opening to me.”
Talking to patients about cannabis use is a “20-minute conversation that details what they’re doing,” he said. He proceeds by asking questions: Are you using for recreational or medicinal purposes? What do you take? What do you take it for? Does it work?
“People will tell you,” Dr. Shubrook said. “They know exactly what it works or doesn’t work for and how it affects their glucose control, which in most cases is only minimally.”
He tells patients he would prefer they don’t inhale cannabis, given the risks posed to the lungs.
“Edibles may have a slower onset of effect, but depending on what they’re adding it to, glucose might be affected,” he noted. “And I have seen that chronic use can lead to hyperemesis syndrome.”
Overall, he said, “Take the time to talk to your patients about cannabis — it will allow them to be honest with you, and you can improve the specificity and safety of its use. If cannabis is legal in your state, encourage people to go to legal dispensaries, which will reduce the risk of it being laced with another drug that could increase the danger of use.”
A recent US prevalence study found that people with diabetes who use cannabis likely engage in other substance and psychoactive substance use, including tobacco use, binge drinking, and misuse of opioids and stimulants.
“Use of these additional substances could further exacerbate the health risks associated with diabetes and also emphasizes the importance of addressing polysubstance use among adults with diabetes,” the study’s author Benjamin H. Han, MD, Division of Geriatrics, Gerontology and Palliative Care, Department of Medicine, US San Diego School of Medicine in La Jolla, California, told this news organization.
“We were surprised at how strong the associations were, especially with use of substances that can increase cardiovascular risk,” Dr. Han added. “And given the strong association we found between cannabis use and use of other psychoactive substances in diabetes, clinicians must screen all their patients for psychoactive substance use.”
Diabetes Canada’s position paper states that despite the limited evidence, “there were sufficient data to begin developing recommendations for type 1 and type 2 diabetes about education, counseling, and management related to recreational cannabis use.”
Their recommendations include the following:
- Healthcare professionals should engage their patients in discussions about substance use on a regular basis, with a nonjudgmental approach.
- The use of recreational cannabis is not recommended for adolescents and adults with diabetes.
- People with T1D should avoid recreational cannabis use because of the increased risk for diabetic ketoacidosis.
- For adults with T1D or T2D who intend to use cannabis recreationally, individualized assessment and counseling should be offered to inform them of the general risks of cannabis, with a focus on harm reduction and reduction of the risk for potential adverse effects on diabetes management and complications.
- People with T1D or T2D should be offered education on and encouraged to read public information available through resources from various Canadian health authorities about the general risks of cannabis use to reduce the risk for nondiabetes-related adverse effects of cannabis consumption.
Of note, in 2018, the Canadian government produced an exhaustive compendium of information on cannabis for healthcare professionals that includes information relevant to managing patients with diabetes.
Dr. Shubrook and Dr. Han reported no competing interests.
A version of this article appeared on Medscape.com.
A recent US prevalence study estimated that 9% adults with diabetes used cannabis in the last month, a 33.7% increase between 2021 and 2022. Nearly half (48.9%) of users were younger than 50 years.
Cannabis use is also increasing sharply among those aged 65 years or older, many of whom have diabetes and other chronic conditions. In this demographic, the perceived risk surrounding regular cannabis use has dropped significantly, even as the data tell another story — that they are particularly at risk from emergency department visits for cannabis poisoning.
As legalization continues and cannabis products proliferate, endocrinologists will likely face more patients of all ages seeking advice about its use. Yet with few evidence-based resources to turn to, endocrinologists advising patients in this area are mostly left fending for themselves.
Evidence ‘Limited’
“The evidence on cannabis is limited mainly because of its scheduling in the United States,” Jay Shubrook, DO, a professor and diabetologist at College of Osteopathic Medicine, Touro University California, in Vallejo, California, told this news organization.
“It was declared to be a schedule I drug in the 1970s, which meant it was ‘dangerous’ and ‘had no medical benefit.’ This made it hard to access and study in human trials.”
That will likely change soon. On May 16, 2024, the US Department of Justice submitted a proposal to move marijuana from a schedule I to a schedule III drug under the Controlled Substances Act, emphasizing its accepted medical use. If approved, the door will open to more investigators seeking to study the effects of cannabis.
Yet, even in Canada, where recreational use has been legal since 2018 and cannabis is sold widely with government support, there are little hard data to guide practice. In 2019, Diabetes Canada issued a position statement on recreational cannabis use in people with type 1 diabetes (T1D) and type 2 diabetes (T2D). It sought to evaluate the effects of cannabis on metabolic factors and diabetes complications, as well as self-management behaviors in those aged 13 years or older.
The authors noted that five of the six studies upon which the statement was based did not consider or report the routes of cannabis administration, which have differing risks. In addition, their recommendations were based on grade D evidence and consensus.
What Patients Are Taking
Cannabis — also known as marijuana, weed, pot, or bud — refers to the dried flowers, leaves, stems, and seeds of the cannabis plant. The plant contains more than 100 compounds, including tetrahydrocannabinol (THC), which is responsible for the euphoric “high,” and other active compounds, including cannabidiol (CBD), which by itself is not mind-altering.
Cannabis can be ingested in several ways. It can be smoked (ie, joints, blunts, pipes, and water pipes), ingested in edible form (mixed or infused into foods), and inhaled using electronic vaporizing devices (ie, e-cigarettes or vape pens).
Compounds in cannabis can also be extracted to make oils and concentrates that can be vaped or inhaled. Smoking oils, concentrates, and extracts from the cannabis plant, known as “dabbing,” are on the rise in the United States.
There are no validated or standard dosage recommendations for cannabis strains and formulations, THC/CBD ratios, or modes of administration. Therefore, the Canadian Pharmacists Association prepared a guide for finding a safe and effective dose for medical purposes. GoodRx, a website with information on prescription drug prices, says that larger doses of THC pose greater risks, noting that the potency of cannabis has increased from 4% in 1995 to about 14% in 2019.
Potential Risks and Benefits: Canadian and US Perspectives
Health and safety risks vary with each of the different ways of using cannabis for individuals with and without diabetes, depending on a host of patient- and product-specific factors.
In a recent article proposing a “THC unit” for Canada’s legal cannabis market, researchers reported that consumers lack familiarity with THC levels, don’t know what constitutes a “low” or “high” THC amount, have trouble dosing, overconsume, and commonly experience adverse health events from cannabis use.
A recent study suggested that most clinicians are similarly uninformed, with “a lack of knowledge of beneficial effects, adverse effects, and of how to advise patients,” even for medical cannabis.
Diabetes Canada takes a stab at summarizing what’s known with respect to cannabis and diabetes, stating that:
“Research on recreational cannabis use suggests it may negatively impact diabetes metabolic factors and self-management behaviors. The safety of recreational cannabis use has not been demonstrated, whereas regular cannabis use is associated with worsening glycemic control, more diabetes-related complications, and poorer self-care behaviors, such as adequate glucose monitoring, adherence to medications, and compliance with dietary and physical activity recommendations for people living with both type 1 and type 2 diabetes.”
The American Diabetes Association’s information on cannabis consists of a patient-oriented article on CBD oil. The article stated:
“There’s a lot of hype surrounding CBD oil and diabetes. There is no noticeable effect on blood glucose (blood sugar) or insulin levels in people with type 2 diabetes. Researchers continue to study the effects of CBD on diabetes in animal studies.”
It concludes that:
“Although many claims continue to be made about CBD oil, there is little evidence of any benefit. It’s certainly not an alternative to traditional diabetes management. The safety of CBD is also unknown — it may have dangerous side effects that we won’t know about unless further research is done.”
A Roundup of Recent Studies
A smattering of recent studies have touched on various aspects of cannabis consumption and diabetes.
Angela Bryan, PhD, professor and co-director of CUChange at the University of Colorado Boulder, has been evaluating cannabis use in young adults (ages 21-40 years) in the SONIC study. Dr. Bryan reported at the American Diabetes Association (ADA) 84th Scientific Sessions that cannabis users were more likely to have a lower body mass index and less likely to develop T2D. Furthermore, chronic cannabis users were less likely to have measures of inflammation and no loss of insulin sensitivity.
Another study by Dr. Bryan’s group found that CBD-dominant forms of cannabis were associated with acute tension reduction, which might lead to longer-term reductions in anxiety. Bryan said the findings could be relevant in the context of diabetes distress.
Similarly positive results were found in a 15-week, double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD spray for neuropathic pain among treatment-resistant patients. The investigators reported that “clinically important improvements” were seen in pain, sleep quality, and subjective impressions of pain. Another small study of inhaled cannabis in treatment-refractory patients found a dose-dependent reduction in diabetic peripheral neuropathy pain.
Findings from a 9-year longitudinal study of approximately 18,000 Swedish men and women suggested no association between cannabis and subsequent T2D development after controlling for age, although these authors also called for longer follow-up and more detailed information about cannabis use to make “more robust” conclusions.
On the other side of the spectrum, a “rapid” review of recreational cannabis use in people with T1D and T2D found that recreational cannabis use may negatively impact diabetes metabolic factors and self-management behaviors and may increase risks for peripheral arterial occlusion, myocardial infarction, and renal disease. However, the authors cautioned that more robust research is needed to confirm the potential impact of cannabis on diabetes.
How to Advise Patients
When Dr. Shubrook was working with patients with diabetes in his family medicine practice in Ohio, cannabis wasn’t legal.
“’Don’t ask, don’t tell’ was the way we handled it then,” he said.
By contrast, in California, where he’s currently located, “it’s pretty well accepted and legal, and patients volunteer information about use, even if it’s recreational,” he said. “Realizing this was something we could talk about was really eye-opening to me.”
Talking to patients about cannabis use is a “20-minute conversation that details what they’re doing,” he said. He proceeds by asking questions: Are you using for recreational or medicinal purposes? What do you take? What do you take it for? Does it work?
“People will tell you,” Dr. Shubrook said. “They know exactly what it works or doesn’t work for and how it affects their glucose control, which in most cases is only minimally.”
He tells patients he would prefer they don’t inhale cannabis, given the risks posed to the lungs.
“Edibles may have a slower onset of effect, but depending on what they’re adding it to, glucose might be affected,” he noted. “And I have seen that chronic use can lead to hyperemesis syndrome.”
Overall, he said, “Take the time to talk to your patients about cannabis — it will allow them to be honest with you, and you can improve the specificity and safety of its use. If cannabis is legal in your state, encourage people to go to legal dispensaries, which will reduce the risk of it being laced with another drug that could increase the danger of use.”
A recent US prevalence study found that people with diabetes who use cannabis likely engage in other substance and psychoactive substance use, including tobacco use, binge drinking, and misuse of opioids and stimulants.
“Use of these additional substances could further exacerbate the health risks associated with diabetes and also emphasizes the importance of addressing polysubstance use among adults with diabetes,” the study’s author Benjamin H. Han, MD, Division of Geriatrics, Gerontology and Palliative Care, Department of Medicine, US San Diego School of Medicine in La Jolla, California, told this news organization.
“We were surprised at how strong the associations were, especially with use of substances that can increase cardiovascular risk,” Dr. Han added. “And given the strong association we found between cannabis use and use of other psychoactive substances in diabetes, clinicians must screen all their patients for psychoactive substance use.”
Diabetes Canada’s position paper states that despite the limited evidence, “there were sufficient data to begin developing recommendations for type 1 and type 2 diabetes about education, counseling, and management related to recreational cannabis use.”
Their recommendations include the following:
- Healthcare professionals should engage their patients in discussions about substance use on a regular basis, with a nonjudgmental approach.
- The use of recreational cannabis is not recommended for adolescents and adults with diabetes.
- People with T1D should avoid recreational cannabis use because of the increased risk for diabetic ketoacidosis.
- For adults with T1D or T2D who intend to use cannabis recreationally, individualized assessment and counseling should be offered to inform them of the general risks of cannabis, with a focus on harm reduction and reduction of the risk for potential adverse effects on diabetes management and complications.
- People with T1D or T2D should be offered education on and encouraged to read public information available through resources from various Canadian health authorities about the general risks of cannabis use to reduce the risk for nondiabetes-related adverse effects of cannabis consumption.
Of note, in 2018, the Canadian government produced an exhaustive compendium of information on cannabis for healthcare professionals that includes information relevant to managing patients with diabetes.
Dr. Shubrook and Dr. Han reported no competing interests.
A version of this article appeared on Medscape.com.
A recent US prevalence study estimated that 9% adults with diabetes used cannabis in the last month, a 33.7% increase between 2021 and 2022. Nearly half (48.9%) of users were younger than 50 years.
Cannabis use is also increasing sharply among those aged 65 years or older, many of whom have diabetes and other chronic conditions. In this demographic, the perceived risk surrounding regular cannabis use has dropped significantly, even as the data tell another story — that they are particularly at risk from emergency department visits for cannabis poisoning.
As legalization continues and cannabis products proliferate, endocrinologists will likely face more patients of all ages seeking advice about its use. Yet with few evidence-based resources to turn to, endocrinologists advising patients in this area are mostly left fending for themselves.
Evidence ‘Limited’
“The evidence on cannabis is limited mainly because of its scheduling in the United States,” Jay Shubrook, DO, a professor and diabetologist at College of Osteopathic Medicine, Touro University California, in Vallejo, California, told this news organization.
“It was declared to be a schedule I drug in the 1970s, which meant it was ‘dangerous’ and ‘had no medical benefit.’ This made it hard to access and study in human trials.”
That will likely change soon. On May 16, 2024, the US Department of Justice submitted a proposal to move marijuana from a schedule I to a schedule III drug under the Controlled Substances Act, emphasizing its accepted medical use. If approved, the door will open to more investigators seeking to study the effects of cannabis.
Yet, even in Canada, where recreational use has been legal since 2018 and cannabis is sold widely with government support, there are little hard data to guide practice. In 2019, Diabetes Canada issued a position statement on recreational cannabis use in people with type 1 diabetes (T1D) and type 2 diabetes (T2D). It sought to evaluate the effects of cannabis on metabolic factors and diabetes complications, as well as self-management behaviors in those aged 13 years or older.
The authors noted that five of the six studies upon which the statement was based did not consider or report the routes of cannabis administration, which have differing risks. In addition, their recommendations were based on grade D evidence and consensus.
What Patients Are Taking
Cannabis — also known as marijuana, weed, pot, or bud — refers to the dried flowers, leaves, stems, and seeds of the cannabis plant. The plant contains more than 100 compounds, including tetrahydrocannabinol (THC), which is responsible for the euphoric “high,” and other active compounds, including cannabidiol (CBD), which by itself is not mind-altering.
Cannabis can be ingested in several ways. It can be smoked (ie, joints, blunts, pipes, and water pipes), ingested in edible form (mixed or infused into foods), and inhaled using electronic vaporizing devices (ie, e-cigarettes or vape pens).
Compounds in cannabis can also be extracted to make oils and concentrates that can be vaped or inhaled. Smoking oils, concentrates, and extracts from the cannabis plant, known as “dabbing,” are on the rise in the United States.
There are no validated or standard dosage recommendations for cannabis strains and formulations, THC/CBD ratios, or modes of administration. Therefore, the Canadian Pharmacists Association prepared a guide for finding a safe and effective dose for medical purposes. GoodRx, a website with information on prescription drug prices, says that larger doses of THC pose greater risks, noting that the potency of cannabis has increased from 4% in 1995 to about 14% in 2019.
Potential Risks and Benefits: Canadian and US Perspectives
Health and safety risks vary with each of the different ways of using cannabis for individuals with and without diabetes, depending on a host of patient- and product-specific factors.
In a recent article proposing a “THC unit” for Canada’s legal cannabis market, researchers reported that consumers lack familiarity with THC levels, don’t know what constitutes a “low” or “high” THC amount, have trouble dosing, overconsume, and commonly experience adverse health events from cannabis use.
A recent study suggested that most clinicians are similarly uninformed, with “a lack of knowledge of beneficial effects, adverse effects, and of how to advise patients,” even for medical cannabis.
Diabetes Canada takes a stab at summarizing what’s known with respect to cannabis and diabetes, stating that:
“Research on recreational cannabis use suggests it may negatively impact diabetes metabolic factors and self-management behaviors. The safety of recreational cannabis use has not been demonstrated, whereas regular cannabis use is associated with worsening glycemic control, more diabetes-related complications, and poorer self-care behaviors, such as adequate glucose monitoring, adherence to medications, and compliance with dietary and physical activity recommendations for people living with both type 1 and type 2 diabetes.”
The American Diabetes Association’s information on cannabis consists of a patient-oriented article on CBD oil. The article stated:
“There’s a lot of hype surrounding CBD oil and diabetes. There is no noticeable effect on blood glucose (blood sugar) or insulin levels in people with type 2 diabetes. Researchers continue to study the effects of CBD on diabetes in animal studies.”
It concludes that:
“Although many claims continue to be made about CBD oil, there is little evidence of any benefit. It’s certainly not an alternative to traditional diabetes management. The safety of CBD is also unknown — it may have dangerous side effects that we won’t know about unless further research is done.”
A Roundup of Recent Studies
A smattering of recent studies have touched on various aspects of cannabis consumption and diabetes.
Angela Bryan, PhD, professor and co-director of CUChange at the University of Colorado Boulder, has been evaluating cannabis use in young adults (ages 21-40 years) in the SONIC study. Dr. Bryan reported at the American Diabetes Association (ADA) 84th Scientific Sessions that cannabis users were more likely to have a lower body mass index and less likely to develop T2D. Furthermore, chronic cannabis users were less likely to have measures of inflammation and no loss of insulin sensitivity.
Another study by Dr. Bryan’s group found that CBD-dominant forms of cannabis were associated with acute tension reduction, which might lead to longer-term reductions in anxiety. Bryan said the findings could be relevant in the context of diabetes distress.
Similarly positive results were found in a 15-week, double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD spray for neuropathic pain among treatment-resistant patients. The investigators reported that “clinically important improvements” were seen in pain, sleep quality, and subjective impressions of pain. Another small study of inhaled cannabis in treatment-refractory patients found a dose-dependent reduction in diabetic peripheral neuropathy pain.
Findings from a 9-year longitudinal study of approximately 18,000 Swedish men and women suggested no association between cannabis and subsequent T2D development after controlling for age, although these authors also called for longer follow-up and more detailed information about cannabis use to make “more robust” conclusions.
On the other side of the spectrum, a “rapid” review of recreational cannabis use in people with T1D and T2D found that recreational cannabis use may negatively impact diabetes metabolic factors and self-management behaviors and may increase risks for peripheral arterial occlusion, myocardial infarction, and renal disease. However, the authors cautioned that more robust research is needed to confirm the potential impact of cannabis on diabetes.
How to Advise Patients
When Dr. Shubrook was working with patients with diabetes in his family medicine practice in Ohio, cannabis wasn’t legal.
“’Don’t ask, don’t tell’ was the way we handled it then,” he said.
By contrast, in California, where he’s currently located, “it’s pretty well accepted and legal, and patients volunteer information about use, even if it’s recreational,” he said. “Realizing this was something we could talk about was really eye-opening to me.”
Talking to patients about cannabis use is a “20-minute conversation that details what they’re doing,” he said. He proceeds by asking questions: Are you using for recreational or medicinal purposes? What do you take? What do you take it for? Does it work?
“People will tell you,” Dr. Shubrook said. “They know exactly what it works or doesn’t work for and how it affects their glucose control, which in most cases is only minimally.”
He tells patients he would prefer they don’t inhale cannabis, given the risks posed to the lungs.
“Edibles may have a slower onset of effect, but depending on what they’re adding it to, glucose might be affected,” he noted. “And I have seen that chronic use can lead to hyperemesis syndrome.”
Overall, he said, “Take the time to talk to your patients about cannabis — it will allow them to be honest with you, and you can improve the specificity and safety of its use. If cannabis is legal in your state, encourage people to go to legal dispensaries, which will reduce the risk of it being laced with another drug that could increase the danger of use.”
A recent US prevalence study found that people with diabetes who use cannabis likely engage in other substance and psychoactive substance use, including tobacco use, binge drinking, and misuse of opioids and stimulants.
“Use of these additional substances could further exacerbate the health risks associated with diabetes and also emphasizes the importance of addressing polysubstance use among adults with diabetes,” the study’s author Benjamin H. Han, MD, Division of Geriatrics, Gerontology and Palliative Care, Department of Medicine, US San Diego School of Medicine in La Jolla, California, told this news organization.
“We were surprised at how strong the associations were, especially with use of substances that can increase cardiovascular risk,” Dr. Han added. “And given the strong association we found between cannabis use and use of other psychoactive substances in diabetes, clinicians must screen all their patients for psychoactive substance use.”
Diabetes Canada’s position paper states that despite the limited evidence, “there were sufficient data to begin developing recommendations for type 1 and type 2 diabetes about education, counseling, and management related to recreational cannabis use.”
Their recommendations include the following:
- Healthcare professionals should engage their patients in discussions about substance use on a regular basis, with a nonjudgmental approach.
- The use of recreational cannabis is not recommended for adolescents and adults with diabetes.
- People with T1D should avoid recreational cannabis use because of the increased risk for diabetic ketoacidosis.
- For adults with T1D or T2D who intend to use cannabis recreationally, individualized assessment and counseling should be offered to inform them of the general risks of cannabis, with a focus on harm reduction and reduction of the risk for potential adverse effects on diabetes management and complications.
- People with T1D or T2D should be offered education on and encouraged to read public information available through resources from various Canadian health authorities about the general risks of cannabis use to reduce the risk for nondiabetes-related adverse effects of cannabis consumption.
Of note, in 2018, the Canadian government produced an exhaustive compendium of information on cannabis for healthcare professionals that includes information relevant to managing patients with diabetes.
Dr. Shubrook and Dr. Han reported no competing interests.
A version of this article appeared on Medscape.com.
AI-Assisted Pathology Poised to Transform Liver Disease Care
Although the technology is not yet approved for routine clinical use, it’s constantly improving and aims to address the limitations inherent in today’s pathology processes.
“You do a biopsy, but instead of having a pathologist read it with their very rough scores of stage 1, 2, or 3, you read it by an AI-driven machine that can quantify it with a score of 1.5 or 1.75 instead of 1 or 2,” Vlad Ratziu, MD, PhD, professor of hepatology at the Sorbonne Université and Hôpital Pitié-Salpêtrière Medical School in Paris, France, and coeditor of The Journal of Hepatology, said in an interview.
“The technology is automated, more sensitive to change, and more highly quantitative. It has implications for liver disease diagnoses, clinical trials, and treatments,” added Dr. Ratziu, who has written about the promise and challenges inherent in developing treatments for metabolic dysfunction–associated steatotic liver disease (MASLD).
To explore the potential impact of AI-powered technologies for the clinic, this news organization spoke with representatives from three companies identified by Dr. Ratziu as leaders in the field: HistoIndex, PathAI, and PharmaNest. Each company uses proprietary technology augmented by AI, and their tools have been used in published trials.
Moving Toward Better Diagnoses and Disease Management
The traditional approach for staging liver fibrosis relies on trained pathologists manually evaluating stained tissue samples obtained from biopsies of the liver.
But this method, though still considered the gold standard, doesn’t always provide the granularity needed for an accurate diagnosis or a reliable assessment in clinical trials, said Dean Tai, PhD, HistoIndex’s cofounder and chief scientific officer.
Although noninvasive tests (NITs), alone or with traditional histologic examination, are increasingly used during clinical management because they are less invasive and more repeatable for disease monitoring, they are limited in their precision and ability to provide comprehensive information, Dr. Tai said. That’s because “no single NIT or single-dimensional measurement of a biomarker offers a full assessment of disease activity, fibrogenic drive, and fibrosis load.”
In contrast, AI provides “a highly reproducible and objective assessment of liver fibrosis severity,” he said. “It eliminates the variability associated with staining methods, while revealing changes in the nano-architecture and morphology of collagen fibers not discernible by the human eye or current NITs, especially in the early stages of fibrosis or in cases of simultaneous progression and regression.”
Mathieu Petitjean, PhD, founder and CEO of PharmaNest, has a similar view.
Although degree of liver fibrosis is associated with long-term outcomes of patients with MASLD, “poor detection thresholds due to their categorical nature mean that small and relevant changes are not reflected by changes in staging,” he said. “The reliable detection [with AI] of subtle changes in the phenotypes of fibrosis will significantly enrich the understanding of progression and regression of fibrosis severity.”
The ability of AI-based tools to see patterns the human eye cannot also means they could “help in predicting which patient may respond to a drug, in order to get the right treatments to the right patients as soon as possible,” said Katy Wack, PhD, vice president of clinical development at PathAI.
“Additionally, AI-based algorithms have been developed to provide more quantitative continuous scores to better capture change and discover new tissue-based biomarkers, which may be prognostic or predictive of clinical benefit,” she said.
Such tools are currently undergoing testing and validation for use in trials and diagnostically.
The standardization and reproducibility offered by AI-driven technology could facilitate more consistent diagnoses across different healthcare settings, Dr. Tai suggested. “As the integration of the technology with other blood-, imaging-, and omics-based techniques evolves, it may enable earlier detection of liver diseases, more accurate monitoring of disease progression, and better evaluation of treatment responses, ultimately improving patient care and outcomes.”
More Effective Clinical Trials
The limitations of conventional pathology may be responsible, at least in part, for the repeated failure of novel compounds to move from phase 2 to phase 3 clinical trials, and from clinical trials to approval, the sources agreed.
“In clinical trials, patients are subject to enrollment criteria using liver biopsies, which are scored with a composite scoring system involving four different histologic components to grade and stage the disease,” Dr. Wack noted.
However, there is wide variability between pathologists on biopsy scoring, and an individual pathologist presented with the same sample may give it a different score after some time has passed, she said.
That means “we are using a nonstandardized and inconsistent scoring system to determine whether a patient can be enrolled or not into a trial,” Dr. Wack said.
The change in the composite score over a follow-up period, usually 1-2 years, determines whether a patient has responded to the candidate drug and, ultimately, whether that drug could be considered for approval, Dr. Wack said.
Because scores at the baseline and follow-up timepoints are not precise and inconsistent across pathologist readers, and even the same reader over time, there are often many “false-positive” and “false-negative” responses that can result in potential therapeutics either failing or succeeding in clinical trials, she said.
To address this variability in biopsy scoring as it relates to clinical trials, regulatory bodies have recommended a consensus approach, in which multiple pathologists read the same biopsy independently and a median score is used, or pathologists convene to come to an agreement, Dr. Wack said.
“This is a very costly and burdensome approach and is still subject to interconsensus panel variation,” she said.
The introduction of digital pathology using validated digital viewers, where pathologists can view a glass slide digitally and pan and zoom over the image as they can with a microscope, means that many pathologists can read the same slide in parallel, she explained.
“If they need to discuss, they can do so efficiently over a phone call, each using their own computer screen and shared annotation tools to facilitate their discussion.”
Although this consensus approach can improve consistency, it still leads to variability in scoring across different groups of pathologists, Dr. Wack said.
This is where AI-assisted pathology comes into play.
“With this approach, a pathologist still views the image digitally, but an algorithm has predicted and highlighted key features and recommended quantitative scores,” she said.
This approach has been shown to increase precision for pathologists, thereby increasing reproducibility and standardizing scoring across timepoints and clinical trials.
What’s Ahead
These AI tools could address pathology’s lack of scalability, the result of a limited number of trained pathologists capable of doing liver biopsy assessments, Dr. Tai said.
“Digital pathology workflows enable the transformation of conventional histologic glass slides into large digital images using scanners, allowing significant productivity gains in terms of workflow and collaboration,” he said.
Although AI-assisted pathology tools are still being validated, their promise for improving diagnoses and uncovering new treatments is clear, the interviewees agreed.
Extending its use to stage fibrosis in other liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and alcoholic liver disease, is also in progress on an experimental basis but will take time to validate.
“The landscape will evolve quickly in the coming 3-4 years,” Dr. Petitjean predicted. “To start, their intended use will likely be limited to a decision-support tool to enhance the performance of pathologists and perhaps stratify or triage cases sent for routine vs expert review.”
Dr. Petitjean even suggested that the increasing role of NITs and the amount of data being generated prospectively and retrospectively around liver biomarkers could mean that liver biopsies might not be needed one day.
A version of this article appeared on Medscape.com.
Although the technology is not yet approved for routine clinical use, it’s constantly improving and aims to address the limitations inherent in today’s pathology processes.
“You do a biopsy, but instead of having a pathologist read it with their very rough scores of stage 1, 2, or 3, you read it by an AI-driven machine that can quantify it with a score of 1.5 or 1.75 instead of 1 or 2,” Vlad Ratziu, MD, PhD, professor of hepatology at the Sorbonne Université and Hôpital Pitié-Salpêtrière Medical School in Paris, France, and coeditor of The Journal of Hepatology, said in an interview.
“The technology is automated, more sensitive to change, and more highly quantitative. It has implications for liver disease diagnoses, clinical trials, and treatments,” added Dr. Ratziu, who has written about the promise and challenges inherent in developing treatments for metabolic dysfunction–associated steatotic liver disease (MASLD).
To explore the potential impact of AI-powered technologies for the clinic, this news organization spoke with representatives from three companies identified by Dr. Ratziu as leaders in the field: HistoIndex, PathAI, and PharmaNest. Each company uses proprietary technology augmented by AI, and their tools have been used in published trials.
Moving Toward Better Diagnoses and Disease Management
The traditional approach for staging liver fibrosis relies on trained pathologists manually evaluating stained tissue samples obtained from biopsies of the liver.
But this method, though still considered the gold standard, doesn’t always provide the granularity needed for an accurate diagnosis or a reliable assessment in clinical trials, said Dean Tai, PhD, HistoIndex’s cofounder and chief scientific officer.
Although noninvasive tests (NITs), alone or with traditional histologic examination, are increasingly used during clinical management because they are less invasive and more repeatable for disease monitoring, they are limited in their precision and ability to provide comprehensive information, Dr. Tai said. That’s because “no single NIT or single-dimensional measurement of a biomarker offers a full assessment of disease activity, fibrogenic drive, and fibrosis load.”
In contrast, AI provides “a highly reproducible and objective assessment of liver fibrosis severity,” he said. “It eliminates the variability associated with staining methods, while revealing changes in the nano-architecture and morphology of collagen fibers not discernible by the human eye or current NITs, especially in the early stages of fibrosis or in cases of simultaneous progression and regression.”
Mathieu Petitjean, PhD, founder and CEO of PharmaNest, has a similar view.
Although degree of liver fibrosis is associated with long-term outcomes of patients with MASLD, “poor detection thresholds due to their categorical nature mean that small and relevant changes are not reflected by changes in staging,” he said. “The reliable detection [with AI] of subtle changes in the phenotypes of fibrosis will significantly enrich the understanding of progression and regression of fibrosis severity.”
The ability of AI-based tools to see patterns the human eye cannot also means they could “help in predicting which patient may respond to a drug, in order to get the right treatments to the right patients as soon as possible,” said Katy Wack, PhD, vice president of clinical development at PathAI.
“Additionally, AI-based algorithms have been developed to provide more quantitative continuous scores to better capture change and discover new tissue-based biomarkers, which may be prognostic or predictive of clinical benefit,” she said.
Such tools are currently undergoing testing and validation for use in trials and diagnostically.
The standardization and reproducibility offered by AI-driven technology could facilitate more consistent diagnoses across different healthcare settings, Dr. Tai suggested. “As the integration of the technology with other blood-, imaging-, and omics-based techniques evolves, it may enable earlier detection of liver diseases, more accurate monitoring of disease progression, and better evaluation of treatment responses, ultimately improving patient care and outcomes.”
More Effective Clinical Trials
The limitations of conventional pathology may be responsible, at least in part, for the repeated failure of novel compounds to move from phase 2 to phase 3 clinical trials, and from clinical trials to approval, the sources agreed.
“In clinical trials, patients are subject to enrollment criteria using liver biopsies, which are scored with a composite scoring system involving four different histologic components to grade and stage the disease,” Dr. Wack noted.
However, there is wide variability between pathologists on biopsy scoring, and an individual pathologist presented with the same sample may give it a different score after some time has passed, she said.
That means “we are using a nonstandardized and inconsistent scoring system to determine whether a patient can be enrolled or not into a trial,” Dr. Wack said.
The change in the composite score over a follow-up period, usually 1-2 years, determines whether a patient has responded to the candidate drug and, ultimately, whether that drug could be considered for approval, Dr. Wack said.
Because scores at the baseline and follow-up timepoints are not precise and inconsistent across pathologist readers, and even the same reader over time, there are often many “false-positive” and “false-negative” responses that can result in potential therapeutics either failing or succeeding in clinical trials, she said.
To address this variability in biopsy scoring as it relates to clinical trials, regulatory bodies have recommended a consensus approach, in which multiple pathologists read the same biopsy independently and a median score is used, or pathologists convene to come to an agreement, Dr. Wack said.
“This is a very costly and burdensome approach and is still subject to interconsensus panel variation,” she said.
The introduction of digital pathology using validated digital viewers, where pathologists can view a glass slide digitally and pan and zoom over the image as they can with a microscope, means that many pathologists can read the same slide in parallel, she explained.
“If they need to discuss, they can do so efficiently over a phone call, each using their own computer screen and shared annotation tools to facilitate their discussion.”
Although this consensus approach can improve consistency, it still leads to variability in scoring across different groups of pathologists, Dr. Wack said.
This is where AI-assisted pathology comes into play.
“With this approach, a pathologist still views the image digitally, but an algorithm has predicted and highlighted key features and recommended quantitative scores,” she said.
This approach has been shown to increase precision for pathologists, thereby increasing reproducibility and standardizing scoring across timepoints and clinical trials.
What’s Ahead
These AI tools could address pathology’s lack of scalability, the result of a limited number of trained pathologists capable of doing liver biopsy assessments, Dr. Tai said.
“Digital pathology workflows enable the transformation of conventional histologic glass slides into large digital images using scanners, allowing significant productivity gains in terms of workflow and collaboration,” he said.
Although AI-assisted pathology tools are still being validated, their promise for improving diagnoses and uncovering new treatments is clear, the interviewees agreed.
Extending its use to stage fibrosis in other liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and alcoholic liver disease, is also in progress on an experimental basis but will take time to validate.
“The landscape will evolve quickly in the coming 3-4 years,” Dr. Petitjean predicted. “To start, their intended use will likely be limited to a decision-support tool to enhance the performance of pathologists and perhaps stratify or triage cases sent for routine vs expert review.”
Dr. Petitjean even suggested that the increasing role of NITs and the amount of data being generated prospectively and retrospectively around liver biomarkers could mean that liver biopsies might not be needed one day.
A version of this article appeared on Medscape.com.
Although the technology is not yet approved for routine clinical use, it’s constantly improving and aims to address the limitations inherent in today’s pathology processes.
“You do a biopsy, but instead of having a pathologist read it with their very rough scores of stage 1, 2, or 3, you read it by an AI-driven machine that can quantify it with a score of 1.5 or 1.75 instead of 1 or 2,” Vlad Ratziu, MD, PhD, professor of hepatology at the Sorbonne Université and Hôpital Pitié-Salpêtrière Medical School in Paris, France, and coeditor of The Journal of Hepatology, said in an interview.
“The technology is automated, more sensitive to change, and more highly quantitative. It has implications for liver disease diagnoses, clinical trials, and treatments,” added Dr. Ratziu, who has written about the promise and challenges inherent in developing treatments for metabolic dysfunction–associated steatotic liver disease (MASLD).
To explore the potential impact of AI-powered technologies for the clinic, this news organization spoke with representatives from three companies identified by Dr. Ratziu as leaders in the field: HistoIndex, PathAI, and PharmaNest. Each company uses proprietary technology augmented by AI, and their tools have been used in published trials.
Moving Toward Better Diagnoses and Disease Management
The traditional approach for staging liver fibrosis relies on trained pathologists manually evaluating stained tissue samples obtained from biopsies of the liver.
But this method, though still considered the gold standard, doesn’t always provide the granularity needed for an accurate diagnosis or a reliable assessment in clinical trials, said Dean Tai, PhD, HistoIndex’s cofounder and chief scientific officer.
Although noninvasive tests (NITs), alone or with traditional histologic examination, are increasingly used during clinical management because they are less invasive and more repeatable for disease monitoring, they are limited in their precision and ability to provide comprehensive information, Dr. Tai said. That’s because “no single NIT or single-dimensional measurement of a biomarker offers a full assessment of disease activity, fibrogenic drive, and fibrosis load.”
In contrast, AI provides “a highly reproducible and objective assessment of liver fibrosis severity,” he said. “It eliminates the variability associated with staining methods, while revealing changes in the nano-architecture and morphology of collagen fibers not discernible by the human eye or current NITs, especially in the early stages of fibrosis or in cases of simultaneous progression and regression.”
Mathieu Petitjean, PhD, founder and CEO of PharmaNest, has a similar view.
Although degree of liver fibrosis is associated with long-term outcomes of patients with MASLD, “poor detection thresholds due to their categorical nature mean that small and relevant changes are not reflected by changes in staging,” he said. “The reliable detection [with AI] of subtle changes in the phenotypes of fibrosis will significantly enrich the understanding of progression and regression of fibrosis severity.”
The ability of AI-based tools to see patterns the human eye cannot also means they could “help in predicting which patient may respond to a drug, in order to get the right treatments to the right patients as soon as possible,” said Katy Wack, PhD, vice president of clinical development at PathAI.
“Additionally, AI-based algorithms have been developed to provide more quantitative continuous scores to better capture change and discover new tissue-based biomarkers, which may be prognostic or predictive of clinical benefit,” she said.
Such tools are currently undergoing testing and validation for use in trials and diagnostically.
The standardization and reproducibility offered by AI-driven technology could facilitate more consistent diagnoses across different healthcare settings, Dr. Tai suggested. “As the integration of the technology with other blood-, imaging-, and omics-based techniques evolves, it may enable earlier detection of liver diseases, more accurate monitoring of disease progression, and better evaluation of treatment responses, ultimately improving patient care and outcomes.”
More Effective Clinical Trials
The limitations of conventional pathology may be responsible, at least in part, for the repeated failure of novel compounds to move from phase 2 to phase 3 clinical trials, and from clinical trials to approval, the sources agreed.
“In clinical trials, patients are subject to enrollment criteria using liver biopsies, which are scored with a composite scoring system involving four different histologic components to grade and stage the disease,” Dr. Wack noted.
However, there is wide variability between pathologists on biopsy scoring, and an individual pathologist presented with the same sample may give it a different score after some time has passed, she said.
That means “we are using a nonstandardized and inconsistent scoring system to determine whether a patient can be enrolled or not into a trial,” Dr. Wack said.
The change in the composite score over a follow-up period, usually 1-2 years, determines whether a patient has responded to the candidate drug and, ultimately, whether that drug could be considered for approval, Dr. Wack said.
Because scores at the baseline and follow-up timepoints are not precise and inconsistent across pathologist readers, and even the same reader over time, there are often many “false-positive” and “false-negative” responses that can result in potential therapeutics either failing or succeeding in clinical trials, she said.
To address this variability in biopsy scoring as it relates to clinical trials, regulatory bodies have recommended a consensus approach, in which multiple pathologists read the same biopsy independently and a median score is used, or pathologists convene to come to an agreement, Dr. Wack said.
“This is a very costly and burdensome approach and is still subject to interconsensus panel variation,” she said.
The introduction of digital pathology using validated digital viewers, where pathologists can view a glass slide digitally and pan and zoom over the image as they can with a microscope, means that many pathologists can read the same slide in parallel, she explained.
“If they need to discuss, they can do so efficiently over a phone call, each using their own computer screen and shared annotation tools to facilitate their discussion.”
Although this consensus approach can improve consistency, it still leads to variability in scoring across different groups of pathologists, Dr. Wack said.
This is where AI-assisted pathology comes into play.
“With this approach, a pathologist still views the image digitally, but an algorithm has predicted and highlighted key features and recommended quantitative scores,” she said.
This approach has been shown to increase precision for pathologists, thereby increasing reproducibility and standardizing scoring across timepoints and clinical trials.
What’s Ahead
These AI tools could address pathology’s lack of scalability, the result of a limited number of trained pathologists capable of doing liver biopsy assessments, Dr. Tai said.
“Digital pathology workflows enable the transformation of conventional histologic glass slides into large digital images using scanners, allowing significant productivity gains in terms of workflow and collaboration,” he said.
Although AI-assisted pathology tools are still being validated, their promise for improving diagnoses and uncovering new treatments is clear, the interviewees agreed.
Extending its use to stage fibrosis in other liver diseases, such as primary biliary cholangitis, primary sclerosing cholangitis, and alcoholic liver disease, is also in progress on an experimental basis but will take time to validate.
“The landscape will evolve quickly in the coming 3-4 years,” Dr. Petitjean predicted. “To start, their intended use will likely be limited to a decision-support tool to enhance the performance of pathologists and perhaps stratify or triage cases sent for routine vs expert review.”
Dr. Petitjean even suggested that the increasing role of NITs and the amount of data being generated prospectively and retrospectively around liver biomarkers could mean that liver biopsies might not be needed one day.
A version of this article appeared on Medscape.com.
Will New Obesity Drugs Make Bariatric Surgery Obsolete?
MADRID — In spirited presentations at the annual meeting of the European Association for the Study of Diabetes, Louis J. Aronne, MD, of Weill Cornell Medicine in New York City, made a compelling case that the next generation of obesity medications will make bariatric surgery obsolete, and Francesco Rubino, MD, of King’s College London in England, made an equally compelling case that they will not.
In fact, Dr. Rubino predicted that “metabolic” surgery — new nomenclature reflecting the power of surgery to reduce not only obesity, but also other metabolic conditions, over the long term — will continue and could even increase in years to come.
‘Medical Treatment Will Dominate’
“Obesity treatment is the superhero of treating metabolic disease because it can defeat all of the bad guys at once, not just one, like the other treatments,” Dr. Aronne told meeting attendees. “If you treat somebody’s cholesterol, you’re just treating their cholesterol, and you may actually increase their risk of developing type 2 diabetes (T2D). You treat their blood pressure, you don’t treat their glucose and you don’t treat their lipids — the list goes on and on and on. But by treating obesity, if you can get enough weight loss, you can get all those things at once.”
He pointed to the SELECT trial, which showed that treating obesity with a glucagon-like peptide 1 receptor agonist reduced major adverse cardiovascular events as well as death from any cause, results in line with those from other modes of treatment for cardiovascular disease (CVD) or lipid lowering, he said. “But we get much more with these drugs, including positive effects on heart failure, chronic kidney disease, and a 73% reduction in T2D. So, we’re now on the verge of a major change in the way we manage metabolic disease.”
Dr. Aronne drew a parallel between treating obesity and the historic way of treating hypertension. Years ago, he said, “we waited too long to treat people. We waited until they had severe hypertension that in many cases was irreversible. What would you prefer to do now for obesity — have the patient lose weight with a medicine that is proven to reduce complications or wait until they develop diabetes, high blood pressure, heart disease and then have them undergo surgery to treat that?”
Looking ahead, “the trend could be to treat obesity before it gets out of hand,” he suggested. Treatment might start in people with a body mass index (BMI) of 27 kg/m2, who would be treated to a target BMI of 25. “That’s only a 10% or so change, but our goal would be to keep them in the normal range so they never go above that target. In fact, I think we’re going to be looking at people with severe obesity in a few years and saying, ‘I can’t believe someone didn’t treat that guy earlier.’ What’s going to happen to bariatric surgery if no one gets to a higher weight?”
The plethora of current weight-loss drugs and the large group on the horizon mean that if someone doesn’t respond to one drug, there will be plenty of other choices, Dr. Aronne continued. People will be referred for surgery, but possibly only after they’ve not responded to medical treatment — or just the opposite. “In the United States, it’s much cheaper to have surgery, and I bet the insurance companies are going to make people have surgery before they can get the medicines,” he acknowledged.
A recent report from Morgan Stanley suggests that the global market for the newer weight-loss drugs could increase by 15-fold over the next 5 years as their benefits expand beyond weight loss and that as much as 9% of the US population will be taking the drugs by 2035, Dr. Aronne said, adding that he thinks 9% is an underestimate. By contrast, the number of patients treated by his team’s surgical program is down about 20%.
“I think it’s very clear that medical treatment is going to dominate,” he concluded. “But, it’s also possible that surgery could go up because so many people are going to be coming for medical therapy that we may wind up referring more for surgical therapy.”
‘Surgery Is Saving Lives’
Dr. Rubino is convinced that anti-obesity drugs will not make surgery obsolete, “but it will not be business as usual,” he told meeting attendees. “In fact, I think these drugs will expedite a process that is already ongoing — a transformation of bariatric into metabolic surgery.”
“Bariatric surgery will go down in history as one of the biggest missed opportunities that we, as medical professionals, have seen over the past many years,” he said. “It has been shown beyond any doubt to reduce all-cause mortality — in other words, it saves lives,” and it’s also cost effective and improves quality of life. Yet, fewer than 1% of people globally who meet the criteria actually get the surgery.
Many clinicians don’t inform patients about the treatment and don’t refer them for it, he said. “That would be equivalent to having surgery for CVD [cardiovascular disease], cancer, or other important diseases available but not being accessed as they should be.”
A big reason for the dearth of procedures is that people have unrealistic expectations about diet and exercise interventions for weight loss, he said. His team’s survey, presented at the 26th World Congress of the International Federation for the Surgery of Obesity and Metabolic Disorders, showed that 43% of respondents believed diet and exercise was the best treatment for severe obesity (BMI > 35). A more recent survey asked which among several choices was the most effective weight-loss intervention, and again a large proportion “believed wrongly that diet and exercise is most effective — more so than drugs or surgery — despite plenty of evidence that this is not the case.”
In this context, he said, “any surgery, no matter how safe or effective, would never be very popular.” If obesity is viewed as a modifiable risk factor, patients may say they’ll think about it for 6 months. In contrast, “nobody will tell you ‘I will think about it’ if you tell them they need gallbladder surgery to get rid of gallstone pain.”
Although drugs are available to treat obesity, none of them are curative, and if they’re stopped, the weight comes back, Dr. Rubino pointed out. “Efficacy of drugs is measured in weeks or months, whereas efficacy of surgery is measured in decades of durability — in the case of bariatric surgery, 10-20 years. That’s why bariatric surgery will remain an option,” he said. “It’s not just preventing disease, it’s resolving ongoing disease.”
Furthermore, bariatric surgery is showing value for people with established T2D, whereas in the past, it was mainly considered to be a weight-loss intervention for younger, healthier patients, he said. “In my practice, we’re operating more often in people with T2D, even those at higher risk for anesthesia and surgery — eg, patients with heart failure, chronic kidney disease, on dialysis — and we’re still able to maintain the same safety with minimally invasive laparoscopic surgery that we had with healthier patients.”
A vote held at the end of the session revealed that the audience was split about half and half in favor of drugs making bariatric surgery obsolete or not.
“I think we may have to duke it out now,” Dr. Aronne quipped.
Dr. Aronne disclosed being a consultant, speaker, and adviser for and receiving research support from Altimmune, Amgen, AstraZeneca, Eli Lilly, Intellihealth, Janssen, Novo Nordisk, Pfizer, Senda, UnitedHealth Group, Versanis, and others; he has ownership interests in ERX, Intellihealth, Jamieson, Kallyope, Skye Bioscience, Veru, and others; and he is on the board of directors of ERX, Jamieson Wellness, and Intellihealth/FlyteHealth. Dr. Rubino disclosed receiving research and educational grants from Novo Nordisk, Ethicon, and Medtronic; he is on the scientific advisory board/data safety advisory board for Keyron, Morphic Medical, and GT Metabolic Solutions; he receives speaking honoraria from Medtronic, Ethicon, Novo Nordisk, and Eli Lilly; and he is president of the nonprofit Metabolic Health Institute.
A version of this article first appeared on Medscape.com.
MADRID — In spirited presentations at the annual meeting of the European Association for the Study of Diabetes, Louis J. Aronne, MD, of Weill Cornell Medicine in New York City, made a compelling case that the next generation of obesity medications will make bariatric surgery obsolete, and Francesco Rubino, MD, of King’s College London in England, made an equally compelling case that they will not.
In fact, Dr. Rubino predicted that “metabolic” surgery — new nomenclature reflecting the power of surgery to reduce not only obesity, but also other metabolic conditions, over the long term — will continue and could even increase in years to come.
‘Medical Treatment Will Dominate’
“Obesity treatment is the superhero of treating metabolic disease because it can defeat all of the bad guys at once, not just one, like the other treatments,” Dr. Aronne told meeting attendees. “If you treat somebody’s cholesterol, you’re just treating their cholesterol, and you may actually increase their risk of developing type 2 diabetes (T2D). You treat their blood pressure, you don’t treat their glucose and you don’t treat their lipids — the list goes on and on and on. But by treating obesity, if you can get enough weight loss, you can get all those things at once.”
He pointed to the SELECT trial, which showed that treating obesity with a glucagon-like peptide 1 receptor agonist reduced major adverse cardiovascular events as well as death from any cause, results in line with those from other modes of treatment for cardiovascular disease (CVD) or lipid lowering, he said. “But we get much more with these drugs, including positive effects on heart failure, chronic kidney disease, and a 73% reduction in T2D. So, we’re now on the verge of a major change in the way we manage metabolic disease.”
Dr. Aronne drew a parallel between treating obesity and the historic way of treating hypertension. Years ago, he said, “we waited too long to treat people. We waited until they had severe hypertension that in many cases was irreversible. What would you prefer to do now for obesity — have the patient lose weight with a medicine that is proven to reduce complications or wait until they develop diabetes, high blood pressure, heart disease and then have them undergo surgery to treat that?”
Looking ahead, “the trend could be to treat obesity before it gets out of hand,” he suggested. Treatment might start in people with a body mass index (BMI) of 27 kg/m2, who would be treated to a target BMI of 25. “That’s only a 10% or so change, but our goal would be to keep them in the normal range so they never go above that target. In fact, I think we’re going to be looking at people with severe obesity in a few years and saying, ‘I can’t believe someone didn’t treat that guy earlier.’ What’s going to happen to bariatric surgery if no one gets to a higher weight?”
The plethora of current weight-loss drugs and the large group on the horizon mean that if someone doesn’t respond to one drug, there will be plenty of other choices, Dr. Aronne continued. People will be referred for surgery, but possibly only after they’ve not responded to medical treatment — or just the opposite. “In the United States, it’s much cheaper to have surgery, and I bet the insurance companies are going to make people have surgery before they can get the medicines,” he acknowledged.
A recent report from Morgan Stanley suggests that the global market for the newer weight-loss drugs could increase by 15-fold over the next 5 years as their benefits expand beyond weight loss and that as much as 9% of the US population will be taking the drugs by 2035, Dr. Aronne said, adding that he thinks 9% is an underestimate. By contrast, the number of patients treated by his team’s surgical program is down about 20%.
“I think it’s very clear that medical treatment is going to dominate,” he concluded. “But, it’s also possible that surgery could go up because so many people are going to be coming for medical therapy that we may wind up referring more for surgical therapy.”
‘Surgery Is Saving Lives’
Dr. Rubino is convinced that anti-obesity drugs will not make surgery obsolete, “but it will not be business as usual,” he told meeting attendees. “In fact, I think these drugs will expedite a process that is already ongoing — a transformation of bariatric into metabolic surgery.”
“Bariatric surgery will go down in history as one of the biggest missed opportunities that we, as medical professionals, have seen over the past many years,” he said. “It has been shown beyond any doubt to reduce all-cause mortality — in other words, it saves lives,” and it’s also cost effective and improves quality of life. Yet, fewer than 1% of people globally who meet the criteria actually get the surgery.
Many clinicians don’t inform patients about the treatment and don’t refer them for it, he said. “That would be equivalent to having surgery for CVD [cardiovascular disease], cancer, or other important diseases available but not being accessed as they should be.”
A big reason for the dearth of procedures is that people have unrealistic expectations about diet and exercise interventions for weight loss, he said. His team’s survey, presented at the 26th World Congress of the International Federation for the Surgery of Obesity and Metabolic Disorders, showed that 43% of respondents believed diet and exercise was the best treatment for severe obesity (BMI > 35). A more recent survey asked which among several choices was the most effective weight-loss intervention, and again a large proportion “believed wrongly that diet and exercise is most effective — more so than drugs or surgery — despite plenty of evidence that this is not the case.”
In this context, he said, “any surgery, no matter how safe or effective, would never be very popular.” If obesity is viewed as a modifiable risk factor, patients may say they’ll think about it for 6 months. In contrast, “nobody will tell you ‘I will think about it’ if you tell them they need gallbladder surgery to get rid of gallstone pain.”
Although drugs are available to treat obesity, none of them are curative, and if they’re stopped, the weight comes back, Dr. Rubino pointed out. “Efficacy of drugs is measured in weeks or months, whereas efficacy of surgery is measured in decades of durability — in the case of bariatric surgery, 10-20 years. That’s why bariatric surgery will remain an option,” he said. “It’s not just preventing disease, it’s resolving ongoing disease.”
Furthermore, bariatric surgery is showing value for people with established T2D, whereas in the past, it was mainly considered to be a weight-loss intervention for younger, healthier patients, he said. “In my practice, we’re operating more often in people with T2D, even those at higher risk for anesthesia and surgery — eg, patients with heart failure, chronic kidney disease, on dialysis — and we’re still able to maintain the same safety with minimally invasive laparoscopic surgery that we had with healthier patients.”
A vote held at the end of the session revealed that the audience was split about half and half in favor of drugs making bariatric surgery obsolete or not.
“I think we may have to duke it out now,” Dr. Aronne quipped.
Dr. Aronne disclosed being a consultant, speaker, and adviser for and receiving research support from Altimmune, Amgen, AstraZeneca, Eli Lilly, Intellihealth, Janssen, Novo Nordisk, Pfizer, Senda, UnitedHealth Group, Versanis, and others; he has ownership interests in ERX, Intellihealth, Jamieson, Kallyope, Skye Bioscience, Veru, and others; and he is on the board of directors of ERX, Jamieson Wellness, and Intellihealth/FlyteHealth. Dr. Rubino disclosed receiving research and educational grants from Novo Nordisk, Ethicon, and Medtronic; he is on the scientific advisory board/data safety advisory board for Keyron, Morphic Medical, and GT Metabolic Solutions; he receives speaking honoraria from Medtronic, Ethicon, Novo Nordisk, and Eli Lilly; and he is president of the nonprofit Metabolic Health Institute.
A version of this article first appeared on Medscape.com.
MADRID — In spirited presentations at the annual meeting of the European Association for the Study of Diabetes, Louis J. Aronne, MD, of Weill Cornell Medicine in New York City, made a compelling case that the next generation of obesity medications will make bariatric surgery obsolete, and Francesco Rubino, MD, of King’s College London in England, made an equally compelling case that they will not.
In fact, Dr. Rubino predicted that “metabolic” surgery — new nomenclature reflecting the power of surgery to reduce not only obesity, but also other metabolic conditions, over the long term — will continue and could even increase in years to come.
‘Medical Treatment Will Dominate’
“Obesity treatment is the superhero of treating metabolic disease because it can defeat all of the bad guys at once, not just one, like the other treatments,” Dr. Aronne told meeting attendees. “If you treat somebody’s cholesterol, you’re just treating their cholesterol, and you may actually increase their risk of developing type 2 diabetes (T2D). You treat their blood pressure, you don’t treat their glucose and you don’t treat their lipids — the list goes on and on and on. But by treating obesity, if you can get enough weight loss, you can get all those things at once.”
He pointed to the SELECT trial, which showed that treating obesity with a glucagon-like peptide 1 receptor agonist reduced major adverse cardiovascular events as well as death from any cause, results in line with those from other modes of treatment for cardiovascular disease (CVD) or lipid lowering, he said. “But we get much more with these drugs, including positive effects on heart failure, chronic kidney disease, and a 73% reduction in T2D. So, we’re now on the verge of a major change in the way we manage metabolic disease.”
Dr. Aronne drew a parallel between treating obesity and the historic way of treating hypertension. Years ago, he said, “we waited too long to treat people. We waited until they had severe hypertension that in many cases was irreversible. What would you prefer to do now for obesity — have the patient lose weight with a medicine that is proven to reduce complications or wait until they develop diabetes, high blood pressure, heart disease and then have them undergo surgery to treat that?”
Looking ahead, “the trend could be to treat obesity before it gets out of hand,” he suggested. Treatment might start in people with a body mass index (BMI) of 27 kg/m2, who would be treated to a target BMI of 25. “That’s only a 10% or so change, but our goal would be to keep them in the normal range so they never go above that target. In fact, I think we’re going to be looking at people with severe obesity in a few years and saying, ‘I can’t believe someone didn’t treat that guy earlier.’ What’s going to happen to bariatric surgery if no one gets to a higher weight?”
The plethora of current weight-loss drugs and the large group on the horizon mean that if someone doesn’t respond to one drug, there will be plenty of other choices, Dr. Aronne continued. People will be referred for surgery, but possibly only after they’ve not responded to medical treatment — or just the opposite. “In the United States, it’s much cheaper to have surgery, and I bet the insurance companies are going to make people have surgery before they can get the medicines,” he acknowledged.
A recent report from Morgan Stanley suggests that the global market for the newer weight-loss drugs could increase by 15-fold over the next 5 years as their benefits expand beyond weight loss and that as much as 9% of the US population will be taking the drugs by 2035, Dr. Aronne said, adding that he thinks 9% is an underestimate. By contrast, the number of patients treated by his team’s surgical program is down about 20%.
“I think it’s very clear that medical treatment is going to dominate,” he concluded. “But, it’s also possible that surgery could go up because so many people are going to be coming for medical therapy that we may wind up referring more for surgical therapy.”
‘Surgery Is Saving Lives’
Dr. Rubino is convinced that anti-obesity drugs will not make surgery obsolete, “but it will not be business as usual,” he told meeting attendees. “In fact, I think these drugs will expedite a process that is already ongoing — a transformation of bariatric into metabolic surgery.”
“Bariatric surgery will go down in history as one of the biggest missed opportunities that we, as medical professionals, have seen over the past many years,” he said. “It has been shown beyond any doubt to reduce all-cause mortality — in other words, it saves lives,” and it’s also cost effective and improves quality of life. Yet, fewer than 1% of people globally who meet the criteria actually get the surgery.
Many clinicians don’t inform patients about the treatment and don’t refer them for it, he said. “That would be equivalent to having surgery for CVD [cardiovascular disease], cancer, or other important diseases available but not being accessed as they should be.”
A big reason for the dearth of procedures is that people have unrealistic expectations about diet and exercise interventions for weight loss, he said. His team’s survey, presented at the 26th World Congress of the International Federation for the Surgery of Obesity and Metabolic Disorders, showed that 43% of respondents believed diet and exercise was the best treatment for severe obesity (BMI > 35). A more recent survey asked which among several choices was the most effective weight-loss intervention, and again a large proportion “believed wrongly that diet and exercise is most effective — more so than drugs or surgery — despite plenty of evidence that this is not the case.”
In this context, he said, “any surgery, no matter how safe or effective, would never be very popular.” If obesity is viewed as a modifiable risk factor, patients may say they’ll think about it for 6 months. In contrast, “nobody will tell you ‘I will think about it’ if you tell them they need gallbladder surgery to get rid of gallstone pain.”
Although drugs are available to treat obesity, none of them are curative, and if they’re stopped, the weight comes back, Dr. Rubino pointed out. “Efficacy of drugs is measured in weeks or months, whereas efficacy of surgery is measured in decades of durability — in the case of bariatric surgery, 10-20 years. That’s why bariatric surgery will remain an option,” he said. “It’s not just preventing disease, it’s resolving ongoing disease.”
Furthermore, bariatric surgery is showing value for people with established T2D, whereas in the past, it was mainly considered to be a weight-loss intervention for younger, healthier patients, he said. “In my practice, we’re operating more often in people with T2D, even those at higher risk for anesthesia and surgery — eg, patients with heart failure, chronic kidney disease, on dialysis — and we’re still able to maintain the same safety with minimally invasive laparoscopic surgery that we had with healthier patients.”
A vote held at the end of the session revealed that the audience was split about half and half in favor of drugs making bariatric surgery obsolete or not.
“I think we may have to duke it out now,” Dr. Aronne quipped.
Dr. Aronne disclosed being a consultant, speaker, and adviser for and receiving research support from Altimmune, Amgen, AstraZeneca, Eli Lilly, Intellihealth, Janssen, Novo Nordisk, Pfizer, Senda, UnitedHealth Group, Versanis, and others; he has ownership interests in ERX, Intellihealth, Jamieson, Kallyope, Skye Bioscience, Veru, and others; and he is on the board of directors of ERX, Jamieson Wellness, and Intellihealth/FlyteHealth. Dr. Rubino disclosed receiving research and educational grants from Novo Nordisk, Ethicon, and Medtronic; he is on the scientific advisory board/data safety advisory board for Keyron, Morphic Medical, and GT Metabolic Solutions; he receives speaking honoraria from Medtronic, Ethicon, Novo Nordisk, and Eli Lilly; and he is president of the nonprofit Metabolic Health Institute.
A version of this article first appeared on Medscape.com.
FROM EASD 2024
GI-Targeted Bitter Hop Extract Curbs Hunger, Food Cravings
TOPLINE:
METHODOLOGY:
- Researchers conducted a randomized, double-blind, crossover study with 30 normal-weight women ages 18-40 with BMIs of 18.5-25. The trial design was similar to that used previously to test the intervention among men.
- Participants engaged in a water-only fast for 24 hours (6 p.m. to 6 p.m.) on three occasions and were given an ad libitum meal to break each fast.
- Participants were randomly assigned to one of three treatments: placebo, a high-dose (500 mg) bitter hop–based appetite suppressant (Amarasate), or a low dose (250 mg) of the appetite suppressant.
- Treatment capsules of half the total dose were given twice daily (16 hours and 20 hours into the fast).
- Participants recorded their subjective feelings about appetite and food cravings using a visual analog scale at 30-minute intervals starting 16 hours into the fast.
TAKEAWAY:
- Both the high-dose and low-dose treatment groups experienced a significant reduction in appetite (ie, hunger, fullness, satisfaction, thoughts of food) and food cravings compared with the placebo group.
- Energy intake at the ad libitum meal was 14.3% lower in the high-dose group than the placebo group (P < .05). It was 8.1% lower in the low-dose group, but the difference was not statistically significant.
- In the high-dose group, two participants reported loose stools and one reported heartburn. In the low-dose group, one participant reported loose stools.
IN PRACTICE:
“These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during fasting in women and show that gastrointestinal delivery of bitter compounds may also be an effective method of reducing cravings for food,” the authors wrote.
SOURCE:
The study, led by Edward Walker, PhD, of the New Zealand Institute for Plant and Food Research Limited, Auckland, New Zealand, was published online in Obesity Pillars.
LIMITATIONS:
The study has limitations that affect its application for weight management. First, the study included only normal-weight individuals, which limits extension of the results for weight loss treatments. Second, it involved acute fasting and does not assess any accommodation to the intervention that may occur over longer-term use. An additional limitation is the small number of participants.
DISCLOSURES:
The research was funded by Calocurb Limited. The article processing charge was funded by the New Zealand Institute for Plant and Food Research Limited, a New Zealand government–owned Crown Research Institute. The authors declare no competing financial interests. The New Zealand Institute for Plant and Food Research Limited has licensed a hop extract as a dietary supplement to Calocurb to commercialize and currently holds a minor shareholding in this company.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a randomized, double-blind, crossover study with 30 normal-weight women ages 18-40 with BMIs of 18.5-25. The trial design was similar to that used previously to test the intervention among men.
- Participants engaged in a water-only fast for 24 hours (6 p.m. to 6 p.m.) on three occasions and were given an ad libitum meal to break each fast.
- Participants were randomly assigned to one of three treatments: placebo, a high-dose (500 mg) bitter hop–based appetite suppressant (Amarasate), or a low dose (250 mg) of the appetite suppressant.
- Treatment capsules of half the total dose were given twice daily (16 hours and 20 hours into the fast).
- Participants recorded their subjective feelings about appetite and food cravings using a visual analog scale at 30-minute intervals starting 16 hours into the fast.
TAKEAWAY:
- Both the high-dose and low-dose treatment groups experienced a significant reduction in appetite (ie, hunger, fullness, satisfaction, thoughts of food) and food cravings compared with the placebo group.
- Energy intake at the ad libitum meal was 14.3% lower in the high-dose group than the placebo group (P < .05). It was 8.1% lower in the low-dose group, but the difference was not statistically significant.
- In the high-dose group, two participants reported loose stools and one reported heartburn. In the low-dose group, one participant reported loose stools.
IN PRACTICE:
“These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during fasting in women and show that gastrointestinal delivery of bitter compounds may also be an effective method of reducing cravings for food,” the authors wrote.
SOURCE:
The study, led by Edward Walker, PhD, of the New Zealand Institute for Plant and Food Research Limited, Auckland, New Zealand, was published online in Obesity Pillars.
LIMITATIONS:
The study has limitations that affect its application for weight management. First, the study included only normal-weight individuals, which limits extension of the results for weight loss treatments. Second, it involved acute fasting and does not assess any accommodation to the intervention that may occur over longer-term use. An additional limitation is the small number of participants.
DISCLOSURES:
The research was funded by Calocurb Limited. The article processing charge was funded by the New Zealand Institute for Plant and Food Research Limited, a New Zealand government–owned Crown Research Institute. The authors declare no competing financial interests. The New Zealand Institute for Plant and Food Research Limited has licensed a hop extract as a dietary supplement to Calocurb to commercialize and currently holds a minor shareholding in this company.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers conducted a randomized, double-blind, crossover study with 30 normal-weight women ages 18-40 with BMIs of 18.5-25. The trial design was similar to that used previously to test the intervention among men.
- Participants engaged in a water-only fast for 24 hours (6 p.m. to 6 p.m.) on three occasions and were given an ad libitum meal to break each fast.
- Participants were randomly assigned to one of three treatments: placebo, a high-dose (500 mg) bitter hop–based appetite suppressant (Amarasate), or a low dose (250 mg) of the appetite suppressant.
- Treatment capsules of half the total dose were given twice daily (16 hours and 20 hours into the fast).
- Participants recorded their subjective feelings about appetite and food cravings using a visual analog scale at 30-minute intervals starting 16 hours into the fast.
TAKEAWAY:
- Both the high-dose and low-dose treatment groups experienced a significant reduction in appetite (ie, hunger, fullness, satisfaction, thoughts of food) and food cravings compared with the placebo group.
- Energy intake at the ad libitum meal was 14.3% lower in the high-dose group than the placebo group (P < .05). It was 8.1% lower in the low-dose group, but the difference was not statistically significant.
- In the high-dose group, two participants reported loose stools and one reported heartburn. In the low-dose group, one participant reported loose stools.
IN PRACTICE:
“These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during fasting in women and show that gastrointestinal delivery of bitter compounds may also be an effective method of reducing cravings for food,” the authors wrote.
SOURCE:
The study, led by Edward Walker, PhD, of the New Zealand Institute for Plant and Food Research Limited, Auckland, New Zealand, was published online in Obesity Pillars.
LIMITATIONS:
The study has limitations that affect its application for weight management. First, the study included only normal-weight individuals, which limits extension of the results for weight loss treatments. Second, it involved acute fasting and does not assess any accommodation to the intervention that may occur over longer-term use. An additional limitation is the small number of participants.
DISCLOSURES:
The research was funded by Calocurb Limited. The article processing charge was funded by the New Zealand Institute for Plant and Food Research Limited, a New Zealand government–owned Crown Research Institute. The authors declare no competing financial interests. The New Zealand Institute for Plant and Food Research Limited has licensed a hop extract as a dietary supplement to Calocurb to commercialize and currently holds a minor shareholding in this company.
A version of this article first appeared on Medscape.com.
Night Owls May Be at Greater Risk for T2D, Beyond Lifestyle
MADRID — research presented at the annual meeting of the European Association for the Study of Diabetes suggested.
In the study, night owls were almost 50% more likely to develop T2D than those who went to sleep earlier.
“The magnitude of this risk was more than I expected, [although] residual confounding may have occurred,” said Jeroen van der Velde, PhD, Leiden University Medical Center in the Netherlands, who presented the study.
“Late chronotype has previously been associated with unhealthy lifestyle and overweight or obesity and, subsequently, cardiometabolic diseases,” he said in an interview. However, although the current study found that individuals with late chronotypes did indeed have larger waists and more visceral fat, “we (and others) believe that lifestyle cannot fully explain the relation between late chronotype and metabolic disorders.”
“In addition,” he noted, “previous studies that observed that late chronotype is associated with overweight or obesity mainly focused on body mass index [BMI]. However, BMI alone does not provide accurate information regarding fat distribution in the body. People with similar BMI may have different underlying fat distribution, and this may be more relevant than BMI for metabolic risk.”
The researchers examined associations between chronotype and BMI, waist circumference, visceral fat, liver fat, and the risk for T2D in a middle-aged population from the Netherlands Epidemiology of Obesity study. Among the 5026 participants, the mean age was 56 years, 54% were women, and mean BMI was 30.
Using data from the study, the study investigators calculated the midpoint of sleep (MPS) and divided participants into three chronotypes: Early MPS < 2:30 PM (20% of participants); intermediate MPS 2:30–4:00 PM (reference category; 60% of participants); and late MPS ≥ 4:00 PM (20% of participants). BMI and waist circumference were measured in all participants, and visceral fat and liver fat were measured in 1576 participants using MRI scans and MR spectroscopy, respectively.
During a median follow-up of 6.6 years, 225 participants were diagnosed with T2D. After adjustment for age, sex, education, physical activity, smoking, alcohol intake, diet quality, sleep quality and duration, and total body fat, participants with a late chronotype had a 46% increased risk for T2D.
Further, those with a late chronotype had 0.7 higher BMI, 1.9-cm larger waist circumference, 7 cm2 more visceral fat, and 14% more liver fat.
Body Clock Out of Sync?
“Late chronotype was associated with increased ectopic body fat and with an increased risk of T2D independent of lifestyle factors and is an emerging risk factor for metabolic diseases,” the researchers concluded.
“A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society,” Dr. van der Velde suggested. “This can lead to circadian misalignment, which we know can lead to metabolic disturbances and ultimately type 2 diabetes.”
Might trying to adjust chronotype earlier in life have an effect on risk?
“Chronotype, as measured via midpoint of sleep, does change a lot in the first 30 years or so in life,” he said. “After that it seems to stabilize. I suppose that if you adapt an intermediate or early chronotype around the age of 30 years, this will help to maintain an earlier chronotype later in life, although we cannot answer this from our study.”
Nevertheless, with respect to T2D risk, “chronotype is likely only part of the puzzle,” he noted.
“People with late chronotypes typically eat late in the evening, and this has also been associated with adverse metabolic effects. At this stage, we do not know if a person changes his/her chronotype that this will also lead to metabolic improvements. More research is needed before we can make recommendations regarding chronotype and timing of other lifestyle behaviors.”
Commenting on the study, Gianluca Iacobellis, MD, PhD, director of the University of Miami Hospital Diabetes Service, Coral Gables, Florida, said: “Interesting data. Altering the physiological circadian rhythm can affect the complex hormonal system — including cortisol, ghrelin, leptin, and serotonin — that regulates insulin sensitivity, glucose, and blood pressure control. The night owl may become more insulin resistant and therefore at higher risk of developing diabetes.”
Like Dr. van der Velde, he noted that “late sleep may be associated with night binging that can cause weight gain and ultimately obesity, further increasing the risk of diabetes.”
Dr. Iacobellis’s group recently showed that vital exhaustion, which is characterized by fatigue and loss of vigor, is associated with a higher cardiovascular risk for and markers of visceral adiposity.
“Abnormal circadian rhythms can be easily associated with vital exhaustion,” he said. Therefore, night owls with more visceral than peripheral fat accumulation might also be at higher cardiometabolic risk through that mechanism.
“However environmental factors and family history can play an important role too,” he added.
Regardless of the mechanisms involved, “preventive actions should be taken to educate teenagers and individuals at higher risk to have healthy sleep habits,” Dr. Iacobellis concluded.
No information regarding funding was provided; Dr. van der Velde and Dr. Iacobellis reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
MADRID — research presented at the annual meeting of the European Association for the Study of Diabetes suggested.
In the study, night owls were almost 50% more likely to develop T2D than those who went to sleep earlier.
“The magnitude of this risk was more than I expected, [although] residual confounding may have occurred,” said Jeroen van der Velde, PhD, Leiden University Medical Center in the Netherlands, who presented the study.
“Late chronotype has previously been associated with unhealthy lifestyle and overweight or obesity and, subsequently, cardiometabolic diseases,” he said in an interview. However, although the current study found that individuals with late chronotypes did indeed have larger waists and more visceral fat, “we (and others) believe that lifestyle cannot fully explain the relation between late chronotype and metabolic disorders.”
“In addition,” he noted, “previous studies that observed that late chronotype is associated with overweight or obesity mainly focused on body mass index [BMI]. However, BMI alone does not provide accurate information regarding fat distribution in the body. People with similar BMI may have different underlying fat distribution, and this may be more relevant than BMI for metabolic risk.”
The researchers examined associations between chronotype and BMI, waist circumference, visceral fat, liver fat, and the risk for T2D in a middle-aged population from the Netherlands Epidemiology of Obesity study. Among the 5026 participants, the mean age was 56 years, 54% were women, and mean BMI was 30.
Using data from the study, the study investigators calculated the midpoint of sleep (MPS) and divided participants into three chronotypes: Early MPS < 2:30 PM (20% of participants); intermediate MPS 2:30–4:00 PM (reference category; 60% of participants); and late MPS ≥ 4:00 PM (20% of participants). BMI and waist circumference were measured in all participants, and visceral fat and liver fat were measured in 1576 participants using MRI scans and MR spectroscopy, respectively.
During a median follow-up of 6.6 years, 225 participants were diagnosed with T2D. After adjustment for age, sex, education, physical activity, smoking, alcohol intake, diet quality, sleep quality and duration, and total body fat, participants with a late chronotype had a 46% increased risk for T2D.
Further, those with a late chronotype had 0.7 higher BMI, 1.9-cm larger waist circumference, 7 cm2 more visceral fat, and 14% more liver fat.
Body Clock Out of Sync?
“Late chronotype was associated with increased ectopic body fat and with an increased risk of T2D independent of lifestyle factors and is an emerging risk factor for metabolic diseases,” the researchers concluded.
“A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society,” Dr. van der Velde suggested. “This can lead to circadian misalignment, which we know can lead to metabolic disturbances and ultimately type 2 diabetes.”
Might trying to adjust chronotype earlier in life have an effect on risk?
“Chronotype, as measured via midpoint of sleep, does change a lot in the first 30 years or so in life,” he said. “After that it seems to stabilize. I suppose that if you adapt an intermediate or early chronotype around the age of 30 years, this will help to maintain an earlier chronotype later in life, although we cannot answer this from our study.”
Nevertheless, with respect to T2D risk, “chronotype is likely only part of the puzzle,” he noted.
“People with late chronotypes typically eat late in the evening, and this has also been associated with adverse metabolic effects. At this stage, we do not know if a person changes his/her chronotype that this will also lead to metabolic improvements. More research is needed before we can make recommendations regarding chronotype and timing of other lifestyle behaviors.”
Commenting on the study, Gianluca Iacobellis, MD, PhD, director of the University of Miami Hospital Diabetes Service, Coral Gables, Florida, said: “Interesting data. Altering the physiological circadian rhythm can affect the complex hormonal system — including cortisol, ghrelin, leptin, and serotonin — that regulates insulin sensitivity, glucose, and blood pressure control. The night owl may become more insulin resistant and therefore at higher risk of developing diabetes.”
Like Dr. van der Velde, he noted that “late sleep may be associated with night binging that can cause weight gain and ultimately obesity, further increasing the risk of diabetes.”
Dr. Iacobellis’s group recently showed that vital exhaustion, which is characterized by fatigue and loss of vigor, is associated with a higher cardiovascular risk for and markers of visceral adiposity.
“Abnormal circadian rhythms can be easily associated with vital exhaustion,” he said. Therefore, night owls with more visceral than peripheral fat accumulation might also be at higher cardiometabolic risk through that mechanism.
“However environmental factors and family history can play an important role too,” he added.
Regardless of the mechanisms involved, “preventive actions should be taken to educate teenagers and individuals at higher risk to have healthy sleep habits,” Dr. Iacobellis concluded.
No information regarding funding was provided; Dr. van der Velde and Dr. Iacobellis reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
MADRID — research presented at the annual meeting of the European Association for the Study of Diabetes suggested.
In the study, night owls were almost 50% more likely to develop T2D than those who went to sleep earlier.
“The magnitude of this risk was more than I expected, [although] residual confounding may have occurred,” said Jeroen van der Velde, PhD, Leiden University Medical Center in the Netherlands, who presented the study.
“Late chronotype has previously been associated with unhealthy lifestyle and overweight or obesity and, subsequently, cardiometabolic diseases,” he said in an interview. However, although the current study found that individuals with late chronotypes did indeed have larger waists and more visceral fat, “we (and others) believe that lifestyle cannot fully explain the relation between late chronotype and metabolic disorders.”
“In addition,” he noted, “previous studies that observed that late chronotype is associated with overweight or obesity mainly focused on body mass index [BMI]. However, BMI alone does not provide accurate information regarding fat distribution in the body. People with similar BMI may have different underlying fat distribution, and this may be more relevant than BMI for metabolic risk.”
The researchers examined associations between chronotype and BMI, waist circumference, visceral fat, liver fat, and the risk for T2D in a middle-aged population from the Netherlands Epidemiology of Obesity study. Among the 5026 participants, the mean age was 56 years, 54% were women, and mean BMI was 30.
Using data from the study, the study investigators calculated the midpoint of sleep (MPS) and divided participants into three chronotypes: Early MPS < 2:30 PM (20% of participants); intermediate MPS 2:30–4:00 PM (reference category; 60% of participants); and late MPS ≥ 4:00 PM (20% of participants). BMI and waist circumference were measured in all participants, and visceral fat and liver fat were measured in 1576 participants using MRI scans and MR spectroscopy, respectively.
During a median follow-up of 6.6 years, 225 participants were diagnosed with T2D. After adjustment for age, sex, education, physical activity, smoking, alcohol intake, diet quality, sleep quality and duration, and total body fat, participants with a late chronotype had a 46% increased risk for T2D.
Further, those with a late chronotype had 0.7 higher BMI, 1.9-cm larger waist circumference, 7 cm2 more visceral fat, and 14% more liver fat.
Body Clock Out of Sync?
“Late chronotype was associated with increased ectopic body fat and with an increased risk of T2D independent of lifestyle factors and is an emerging risk factor for metabolic diseases,” the researchers concluded.
“A likely explanation is that the circadian rhythm or body clock in late chronotypes is out of sync with the work and social schedules followed by society,” Dr. van der Velde suggested. “This can lead to circadian misalignment, which we know can lead to metabolic disturbances and ultimately type 2 diabetes.”
Might trying to adjust chronotype earlier in life have an effect on risk?
“Chronotype, as measured via midpoint of sleep, does change a lot in the first 30 years or so in life,” he said. “After that it seems to stabilize. I suppose that if you adapt an intermediate or early chronotype around the age of 30 years, this will help to maintain an earlier chronotype later in life, although we cannot answer this from our study.”
Nevertheless, with respect to T2D risk, “chronotype is likely only part of the puzzle,” he noted.
“People with late chronotypes typically eat late in the evening, and this has also been associated with adverse metabolic effects. At this stage, we do not know if a person changes his/her chronotype that this will also lead to metabolic improvements. More research is needed before we can make recommendations regarding chronotype and timing of other lifestyle behaviors.”
Commenting on the study, Gianluca Iacobellis, MD, PhD, director of the University of Miami Hospital Diabetes Service, Coral Gables, Florida, said: “Interesting data. Altering the physiological circadian rhythm can affect the complex hormonal system — including cortisol, ghrelin, leptin, and serotonin — that regulates insulin sensitivity, glucose, and blood pressure control. The night owl may become more insulin resistant and therefore at higher risk of developing diabetes.”
Like Dr. van der Velde, he noted that “late sleep may be associated with night binging that can cause weight gain and ultimately obesity, further increasing the risk of diabetes.”
Dr. Iacobellis’s group recently showed that vital exhaustion, which is characterized by fatigue and loss of vigor, is associated with a higher cardiovascular risk for and markers of visceral adiposity.
“Abnormal circadian rhythms can be easily associated with vital exhaustion,” he said. Therefore, night owls with more visceral than peripheral fat accumulation might also be at higher cardiometabolic risk through that mechanism.
“However environmental factors and family history can play an important role too,” he added.
Regardless of the mechanisms involved, “preventive actions should be taken to educate teenagers and individuals at higher risk to have healthy sleep habits,” Dr. Iacobellis concluded.
No information regarding funding was provided; Dr. van der Velde and Dr. Iacobellis reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM EASD 2024
Will Tirzepatide Vials Help Patients? Endos Weigh in
Tirzepatide (Zepbound) is not in shortage for now, but the weight loss drug has remained inaccessible to people without insurance coverage who can’t afford to pay out of pocket. Now, its manufacturer, Eli Lilly, has introduced a new formulation it says will “significantly expand” the supply. But not all endocrinologists are enthusiastic.
As of August 27, LillyDirect made 2.5-mg and 5-mg single-dose vials of tirzepatide available to self-pay patients with an on-label electronic prescription. Lilly’s announcement said the single-dose vials “are priced at a 50% or greater discount compared to the list price of all other incretin (glucagon-like peptide 1 receptor agonists or GLP-1) medicines for obesity.”
For a 4-week supply of the weekly injections, the discount at LillyDirect translates to $399 for a 2.5-mg single-dose vial ($99.75 per vial) and $549 for the 5-mg dose ($137.25 per vial), which the company noted was “in line with the Zepbound savings program for noncovered individuals.” (The new direct single-dose prescriptions cannot be filled at community or retail pharmacies.)
“In a clinical study, the 5-mg maintenance dose helped patients achieve an average of 15% weight loss after 72 weeks of treatment and has been a powerful tool for millions of people with obesity looking to lose weight and keep it off,” according to the announcement.
The clinical study, which is not named or referenced in the announcement, is SURMOUNT-1, a Lilly spokesperson said in an interview. Yet, that study also found that patients achieved an average weight loss of 19.5% with 10-mg doses and 20.9% with 15-mg doses of tirzepatide. Furthermore, the percentage of participants achieving body weight reductions of ≥ 5% was 85% (5 mg), 89% (10 mg), and 91% (15 mg), showing the benefits of higher doses.
And there’s the rub.
‘Only Two Different Doses’
Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the University of Southern California, Los Angeles, said in an interview: “My concern is, they’re only providing two different doses, 2.5 mg and 5 mg. You get somebody on it, and then they still have to go back to the traditional pens. I’m very opposed to getting patients connected to a medication they can’t then continue to take.
“Now we have starter doses that are easy to come by,” she said. “But the problem isn’t starting. The problem for all of these patients is chronic continuation of the right dose of the drug, and out-of-pocket costs become exorbitantly higher when they have to self-purchase the pens for the higher doses.
“Yes, the 5-mg dose has benefits, but not the same as higher doses,” she continued. “I have nobody for whom 5 mg is the right dose. They have to take more, sometimes within a month or 2 of starting, in order to achieve the kind of weight loss they need.”
If their insurance doesn’t cover the drug, “what are they going to do to stay on 5 mg? Or pay a crapload of money to buy three of the 5-mg doses to reach a higher dose?”
Michael Weintraub, MD, clinical assistant professor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism at New York University Grossman School of Medicine in New York City, said that, “for many, this lower monthly cost is attainable and is a significant advancement in increasing access. For others, however, an out-of-pocket monthly cost of $349-549 for a chronic medication is still unaffordable.”
And like Dr. Peters, he said, “some patients do not lose a clinically significant amount of weight with 2.5 mg or 5 mg and require higher doses. There is no way of prescribing a higher dose of Zepbound vials, so patients would have to resort to the higher-dose auto-injector pens that are still double the price.”
A Lilly spokesperson countered in a comment: “Offering Zepbound single-dose vials in higher dosage strengths could increase the potential for dose splitting, which is not contemplated by the FDA [Food and Drug Adminstration]–approved label and may pose patient safety risks.”
But Dr. Peters wondered: “Wouldn’t dose splitting of a known-to-be-pure compound be better than getting it at a compounding pharmacy that lacks purity/safety? The one message from all of this is that patients need to know what they’re getting into. They’re starting a drug that can help with weight loss, but they’re going to be on a sub-max dose. And a higher dose is going to be double the price.”
In addition, said Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, “for the lower-dose vials, instead of administering the drug with a self-auto-injection pen, patients will need to use a needle and syringe and draw up the dose from a vial. This will take a higher skill level and health literacy that may be challenging for some patients. Patients may need additional training on how to use this new formulation. That will take additional time and resources, such as a demonstration in the office or referral to video.”
The Lilly news release noted that “patients can also purchase ancillary supplies, like syringes and needles, and will have access to important patient-friendly instructional materials on correctly administering the medicine via needle and syringe.”
Protection From Compounders?
According to the Lilly spokesperson, the launch of Zepbound vials “furthers our commitment to helping patients avoid the risks associated with compounded products by providing patients another option for access to genuine Lilly medicine.”
Indeed, said Jaime Almandoz, MD, medical director of the Weight Wellness Program and associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, “The introduction of Zepbound/tirzepatide in single-dose vials should improve access to evidence-based obesity treatments, reducing potential risks associated with compounded additives and eliminating the need for patients to calculate correct medication doses,” which have led to accidental overdoses of compounded semaglutide.
Lilly’s spokesperson added: “We have taken multiple steps — including publishing an open letter and launching lilly.com/real-medicine — to warn the public about the risks posed by the proliferation of counterfeit, fake, unsafe, or untested knockoffs of Lilly’s genuine medicines.”
But whether these steps are strong enough to overcome the realities of cost and the need for affordable higher doses remains to be seen.
Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said in a statement that the new version of Zepbound “is great news for patients. It’s a much more rational and care-focused response to the remarkable demand for their drug than the lawsuits and cease-and-desist letters Lilly has been raining down on compounding pharmacies.”
“For 20 months now,” he continued,
Dr. Almandoz affirmed: “Everyone wants to see improved access to evidence-based obesity care. It’s crucial to ensure patients receive the most appropriate interventions, whether it is lifestyle changes, medications, or bariatric surgery,” he said. “There are resources available, [including his recent paper], for nutrition and lifestyle modifications specifically for patients taking obesity medications, which can help clinicians guide their patients toward better health.”
Dr. Almandoz is a member of advisory boards and consults for: Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr. Kushner is an adviser to Eli Lilly and Novo Nordisk. Dr. Peters and Dr. Weintraub declared no competing interests.
A version of this article appeared on Medscape.com.
Tirzepatide (Zepbound) is not in shortage for now, but the weight loss drug has remained inaccessible to people without insurance coverage who can’t afford to pay out of pocket. Now, its manufacturer, Eli Lilly, has introduced a new formulation it says will “significantly expand” the supply. But not all endocrinologists are enthusiastic.
As of August 27, LillyDirect made 2.5-mg and 5-mg single-dose vials of tirzepatide available to self-pay patients with an on-label electronic prescription. Lilly’s announcement said the single-dose vials “are priced at a 50% or greater discount compared to the list price of all other incretin (glucagon-like peptide 1 receptor agonists or GLP-1) medicines for obesity.”
For a 4-week supply of the weekly injections, the discount at LillyDirect translates to $399 for a 2.5-mg single-dose vial ($99.75 per vial) and $549 for the 5-mg dose ($137.25 per vial), which the company noted was “in line with the Zepbound savings program for noncovered individuals.” (The new direct single-dose prescriptions cannot be filled at community or retail pharmacies.)
“In a clinical study, the 5-mg maintenance dose helped patients achieve an average of 15% weight loss after 72 weeks of treatment and has been a powerful tool for millions of people with obesity looking to lose weight and keep it off,” according to the announcement.
The clinical study, which is not named or referenced in the announcement, is SURMOUNT-1, a Lilly spokesperson said in an interview. Yet, that study also found that patients achieved an average weight loss of 19.5% with 10-mg doses and 20.9% with 15-mg doses of tirzepatide. Furthermore, the percentage of participants achieving body weight reductions of ≥ 5% was 85% (5 mg), 89% (10 mg), and 91% (15 mg), showing the benefits of higher doses.
And there’s the rub.
‘Only Two Different Doses’
Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the University of Southern California, Los Angeles, said in an interview: “My concern is, they’re only providing two different doses, 2.5 mg and 5 mg. You get somebody on it, and then they still have to go back to the traditional pens. I’m very opposed to getting patients connected to a medication they can’t then continue to take.
“Now we have starter doses that are easy to come by,” she said. “But the problem isn’t starting. The problem for all of these patients is chronic continuation of the right dose of the drug, and out-of-pocket costs become exorbitantly higher when they have to self-purchase the pens for the higher doses.
“Yes, the 5-mg dose has benefits, but not the same as higher doses,” she continued. “I have nobody for whom 5 mg is the right dose. They have to take more, sometimes within a month or 2 of starting, in order to achieve the kind of weight loss they need.”
If their insurance doesn’t cover the drug, “what are they going to do to stay on 5 mg? Or pay a crapload of money to buy three of the 5-mg doses to reach a higher dose?”
Michael Weintraub, MD, clinical assistant professor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism at New York University Grossman School of Medicine in New York City, said that, “for many, this lower monthly cost is attainable and is a significant advancement in increasing access. For others, however, an out-of-pocket monthly cost of $349-549 for a chronic medication is still unaffordable.”
And like Dr. Peters, he said, “some patients do not lose a clinically significant amount of weight with 2.5 mg or 5 mg and require higher doses. There is no way of prescribing a higher dose of Zepbound vials, so patients would have to resort to the higher-dose auto-injector pens that are still double the price.”
A Lilly spokesperson countered in a comment: “Offering Zepbound single-dose vials in higher dosage strengths could increase the potential for dose splitting, which is not contemplated by the FDA [Food and Drug Adminstration]–approved label and may pose patient safety risks.”
But Dr. Peters wondered: “Wouldn’t dose splitting of a known-to-be-pure compound be better than getting it at a compounding pharmacy that lacks purity/safety? The one message from all of this is that patients need to know what they’re getting into. They’re starting a drug that can help with weight loss, but they’re going to be on a sub-max dose. And a higher dose is going to be double the price.”
In addition, said Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, “for the lower-dose vials, instead of administering the drug with a self-auto-injection pen, patients will need to use a needle and syringe and draw up the dose from a vial. This will take a higher skill level and health literacy that may be challenging for some patients. Patients may need additional training on how to use this new formulation. That will take additional time and resources, such as a demonstration in the office or referral to video.”
The Lilly news release noted that “patients can also purchase ancillary supplies, like syringes and needles, and will have access to important patient-friendly instructional materials on correctly administering the medicine via needle and syringe.”
Protection From Compounders?
According to the Lilly spokesperson, the launch of Zepbound vials “furthers our commitment to helping patients avoid the risks associated with compounded products by providing patients another option for access to genuine Lilly medicine.”
Indeed, said Jaime Almandoz, MD, medical director of the Weight Wellness Program and associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, “The introduction of Zepbound/tirzepatide in single-dose vials should improve access to evidence-based obesity treatments, reducing potential risks associated with compounded additives and eliminating the need for patients to calculate correct medication doses,” which have led to accidental overdoses of compounded semaglutide.
Lilly’s spokesperson added: “We have taken multiple steps — including publishing an open letter and launching lilly.com/real-medicine — to warn the public about the risks posed by the proliferation of counterfeit, fake, unsafe, or untested knockoffs of Lilly’s genuine medicines.”
But whether these steps are strong enough to overcome the realities of cost and the need for affordable higher doses remains to be seen.
Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said in a statement that the new version of Zepbound “is great news for patients. It’s a much more rational and care-focused response to the remarkable demand for their drug than the lawsuits and cease-and-desist letters Lilly has been raining down on compounding pharmacies.”
“For 20 months now,” he continued,
Dr. Almandoz affirmed: “Everyone wants to see improved access to evidence-based obesity care. It’s crucial to ensure patients receive the most appropriate interventions, whether it is lifestyle changes, medications, or bariatric surgery,” he said. “There are resources available, [including his recent paper], for nutrition and lifestyle modifications specifically for patients taking obesity medications, which can help clinicians guide their patients toward better health.”
Dr. Almandoz is a member of advisory boards and consults for: Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr. Kushner is an adviser to Eli Lilly and Novo Nordisk. Dr. Peters and Dr. Weintraub declared no competing interests.
A version of this article appeared on Medscape.com.
Tirzepatide (Zepbound) is not in shortage for now, but the weight loss drug has remained inaccessible to people without insurance coverage who can’t afford to pay out of pocket. Now, its manufacturer, Eli Lilly, has introduced a new formulation it says will “significantly expand” the supply. But not all endocrinologists are enthusiastic.
As of August 27, LillyDirect made 2.5-mg and 5-mg single-dose vials of tirzepatide available to self-pay patients with an on-label electronic prescription. Lilly’s announcement said the single-dose vials “are priced at a 50% or greater discount compared to the list price of all other incretin (glucagon-like peptide 1 receptor agonists or GLP-1) medicines for obesity.”
For a 4-week supply of the weekly injections, the discount at LillyDirect translates to $399 for a 2.5-mg single-dose vial ($99.75 per vial) and $549 for the 5-mg dose ($137.25 per vial), which the company noted was “in line with the Zepbound savings program for noncovered individuals.” (The new direct single-dose prescriptions cannot be filled at community or retail pharmacies.)
“In a clinical study, the 5-mg maintenance dose helped patients achieve an average of 15% weight loss after 72 weeks of treatment and has been a powerful tool for millions of people with obesity looking to lose weight and keep it off,” according to the announcement.
The clinical study, which is not named or referenced in the announcement, is SURMOUNT-1, a Lilly spokesperson said in an interview. Yet, that study also found that patients achieved an average weight loss of 19.5% with 10-mg doses and 20.9% with 15-mg doses of tirzepatide. Furthermore, the percentage of participants achieving body weight reductions of ≥ 5% was 85% (5 mg), 89% (10 mg), and 91% (15 mg), showing the benefits of higher doses.
And there’s the rub.
‘Only Two Different Doses’
Anne Peters, MD, a professor of clinical medicine and a clinical scholar at the University of Southern California, Los Angeles, said in an interview: “My concern is, they’re only providing two different doses, 2.5 mg and 5 mg. You get somebody on it, and then they still have to go back to the traditional pens. I’m very opposed to getting patients connected to a medication they can’t then continue to take.
“Now we have starter doses that are easy to come by,” she said. “But the problem isn’t starting. The problem for all of these patients is chronic continuation of the right dose of the drug, and out-of-pocket costs become exorbitantly higher when they have to self-purchase the pens for the higher doses.
“Yes, the 5-mg dose has benefits, but not the same as higher doses,” she continued. “I have nobody for whom 5 mg is the right dose. They have to take more, sometimes within a month or 2 of starting, in order to achieve the kind of weight loss they need.”
If their insurance doesn’t cover the drug, “what are they going to do to stay on 5 mg? Or pay a crapload of money to buy three of the 5-mg doses to reach a higher dose?”
Michael Weintraub, MD, clinical assistant professor in the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism at New York University Grossman School of Medicine in New York City, said that, “for many, this lower monthly cost is attainable and is a significant advancement in increasing access. For others, however, an out-of-pocket monthly cost of $349-549 for a chronic medication is still unaffordable.”
And like Dr. Peters, he said, “some patients do not lose a clinically significant amount of weight with 2.5 mg or 5 mg and require higher doses. There is no way of prescribing a higher dose of Zepbound vials, so patients would have to resort to the higher-dose auto-injector pens that are still double the price.”
A Lilly spokesperson countered in a comment: “Offering Zepbound single-dose vials in higher dosage strengths could increase the potential for dose splitting, which is not contemplated by the FDA [Food and Drug Adminstration]–approved label and may pose patient safety risks.”
But Dr. Peters wondered: “Wouldn’t dose splitting of a known-to-be-pure compound be better than getting it at a compounding pharmacy that lacks purity/safety? The one message from all of this is that patients need to know what they’re getting into. They’re starting a drug that can help with weight loss, but they’re going to be on a sub-max dose. And a higher dose is going to be double the price.”
In addition, said Robert F. Kushner, MD, a professor at Northwestern University Feinberg School of Medicine in Chicago, Illinois, “for the lower-dose vials, instead of administering the drug with a self-auto-injection pen, patients will need to use a needle and syringe and draw up the dose from a vial. This will take a higher skill level and health literacy that may be challenging for some patients. Patients may need additional training on how to use this new formulation. That will take additional time and resources, such as a demonstration in the office or referral to video.”
The Lilly news release noted that “patients can also purchase ancillary supplies, like syringes and needles, and will have access to important patient-friendly instructional materials on correctly administering the medicine via needle and syringe.”
Protection From Compounders?
According to the Lilly spokesperson, the launch of Zepbound vials “furthers our commitment to helping patients avoid the risks associated with compounded products by providing patients another option for access to genuine Lilly medicine.”
Indeed, said Jaime Almandoz, MD, medical director of the Weight Wellness Program and associate professor of internal medicine at the University of Texas Southwestern Medical Center in Dallas, “The introduction of Zepbound/tirzepatide in single-dose vials should improve access to evidence-based obesity treatments, reducing potential risks associated with compounded additives and eliminating the need for patients to calculate correct medication doses,” which have led to accidental overdoses of compounded semaglutide.
Lilly’s spokesperson added: “We have taken multiple steps — including publishing an open letter and launching lilly.com/real-medicine — to warn the public about the risks posed by the proliferation of counterfeit, fake, unsafe, or untested knockoffs of Lilly’s genuine medicines.”
But whether these steps are strong enough to overcome the realities of cost and the need for affordable higher doses remains to be seen.
Scott Brunner, CEO of the Alliance for Pharmacy Compounding, said in a statement that the new version of Zepbound “is great news for patients. It’s a much more rational and care-focused response to the remarkable demand for their drug than the lawsuits and cease-and-desist letters Lilly has been raining down on compounding pharmacies.”
“For 20 months now,” he continued,
Dr. Almandoz affirmed: “Everyone wants to see improved access to evidence-based obesity care. It’s crucial to ensure patients receive the most appropriate interventions, whether it is lifestyle changes, medications, or bariatric surgery,” he said. “There are resources available, [including his recent paper], for nutrition and lifestyle modifications specifically for patients taking obesity medications, which can help clinicians guide their patients toward better health.”
Dr. Almandoz is a member of advisory boards and consults for: Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr. Kushner is an adviser to Eli Lilly and Novo Nordisk. Dr. Peters and Dr. Weintraub declared no competing interests.
A version of this article appeared on Medscape.com.