Marilynn Larkin

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

Actively drinking patients who undergo screening, a brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during hospital admission for alcohol-related conditions have fewer 30- and 90-day readmissions for alcohol-related liver disease, a new study suggests.

Nevertheless, SBIRT was administered to only 51.7% of patients admitted for alcohol-associated hepatitis (AAH) and 23.7% of patients admitted for decompensated alcohol-related cirrhosis (DARLC). 

“Not only did conducting SBIRT with patients admitted for AAH reduce 30-day and 90-day liver-related readmissions, but even just being offered SBIRT reduced readmissions, too,” study author Dennis Wang, MD, of the adult gastroenterology residency program at McMaster University in Hamilton, Ontario, told this news organization. “The exact reason for this effect is unclear, but one can speculate that offering SBIRT to AAH patients may trigger them to consider abstaining from alcohol.”

By contrast, receiving or being offered SBIRT had no effect on readmissions for patients with DARLC.

The findings were published online on November 30 in the Journal of the Canadian Association of Gastroenterology.

Readmissions Significantly Reduced

The researchers retrospectively reviewed the electronic medical records of patients with AAH or DARLC who were admitted to Hamilton Health Sciences hospitals in Ontario from January 2017 to December 2021. Eligible patients were aged ≥ 18 years and actively drinking.

The study’s primary outcomes were the proportion of admissions in which SBIRT was conducted and the association between conducting SBIRT and 30- and 90-day readmissions for recurrent AAH or DARLC.

There were 120 admissions for AAH, representing 95 patients, 95 index admissions, 18 patients with 30-day readmissions, and 26 patients with 90-day readmissions. The sum of the index AAH admissions and 90-day readmissions was greater than the total number of AAH admissions because readmissions where patients were no longer actively drinking alcohol were included.

There were 177 admissions for DARLC, representing 132 patients, 132 index admissions, 13 30-day readmissions, and 31 90-day readmissions.

The mean age of patients admitted with AAH (47.7 years) was significantly lower than that of patients admitted with DARLC (58.2 years). Fewer men were admitted with AAH (59.2%) than with DARLC (73.4%).

There was no significant difference between AAH admissions and DARLC admissions in hospital length of stay, Model for End-Stage Liver Disease on admission, same-admission mortality, and 30- or 90-day readmissions.

SBIRT was conducted in 62 of 120 AAH admissions (51.7%) and 42 of 177 DARLC admissions (23.7%), mainly by social workers and addiction counselors and occasionally by physicians alone.

“Sometimes patients with AAH or DARLC can become so ill that they cannot participate in SBIRT,” noted Dr. Wang. “In addition, there may not be enough health care providers, resources, or time available to conduct high-quality SBIRT with all patients admitted to hospital.”

For patients with AAH, SBIRT was associated with significantly reduced 30-day (odds ratio [OR], 0.098) and 90-day (OR, 0.166) likelihood of readmission for recurrent AAH. However, there was no association with readmissions for patients with DARLC.

Liver Scarring Persists

“We suspect that DARLC patients do not see the same improvement in liver-related readmissions after receiving SBIRT because the liver scarring typically persists even with alcohol abstinence, and this scarring causes further decompensations,” said Dr. Wang.

“Physicians, social workers, addiction counselors, and other allied health providers should collaborate to conduct SBIRT for all actively drinking patients admitted for AAH or DARLC,” wrote the authors.

The researchers acknowledged that their study was limited by its inclusion of data from only a single center. The admissions for AAH and DARLC had a higher proportion of male patients than female patients, thus limiting the generalizability of the findings. In addition, there was a lack of data on ethnicity and socioeconomic status, which could affect readmissions.

Dr. Wang advises clinicians to “seek out and connect with other healthcare providers in their local and regional community, such as addiction counselors or psychologists, to build a robust referral network for patients wanting to reduce their alcohol use.”

In addition, “providers should become comfortable with asking patients nonjudgmentally about alcohol use, as this builds the initial rapport that lays the foundation for ongoing care,” he said. “Every interaction with a patient is a new opportunity to guide interested patients towards alcohol cessation.”

Multidisciplinary Team Essential

Commenting on the findings, Meena B. Bansal, MD, professor of medicine and director of translational research in liver diseases at the Icahn School of Medicine at Mount Sinai in New York, said that they reflect clinical experience in US hospitals. “Physicians are so busy handling the acute medical situation posed by the admission that while they do certainly tell the patient they should stop drinking, full discussion, intervention, and linkage to outpatient programs is often led by the social worker,” she said. Dr. Bansal was not involved in the study.

“Many alcohol use disorder therapies are not tested in extremely ill patients, and thus, pharmacotherapy is often reserved for outpatient management, when patients are more clinically stable,” she said. Yet, as mentioned by the authors, a recent study “showed that 71% of providers never prescribed pharmacotherapy for alcohol use disorder, with the most common reason being low comfort with the medications. We need to increase education around pharmacotherapy for alcohol use disorder to increase the comfort level of practicing gastroenterologists and hepatologists.”

Furthermore, she said, clinicians need to intervene and provide guidance to patients “wherever and whenever they touch our system, whether that be in the inpatient or outpatient setting, [and] provide SBIRT during inpatient admissions but then follow patients longitudinally in a multidisciplinary team to achieve long-term results.”

The study was conducted without external funding. Dr. Wang had no relevant conflicts to disclose. A coauthor acts as a consultant, clinical trial investigator, speaker, and member of the advisory board for AbbVie, Gilead, Intercept, and Novo Nordisk. He also acts as a speaker and member of the advisory board for Eisai and Lupin and as a clinical trial investigator for Madrigal.

A version of this article appeared on Medscape.com.

The positive results from the SELECT trial for the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were hailed as ushering in a “new era for patients with obesity.” In the trial of overweight and obese patients with cardiovascular disease (CVD), but no diabetes, semaglutide showed meaningful reductions in cardiovascular death, myocardial infarction, and stroke compared with placebo.

“I definitely see increasing adoption of GLP-1 RAs by cardiologists and expect the number to increase now that the data support its use in secondary prevention,” said Nicole L. Lohr, MD, PhD, chair of the American College of Cardiology (ACC) Board of Governors, and Mary G. Waters, chair of cardiovascular medicine at UAB, Birmingham.

But many cardiologists are more hesitant. “I think there’s going to be an increasing urgency for cardiologists to start prescribing these drugs, but I don’t think the comfort to do so is that widespread at this point,” said American Heart Association (AHA) volunteer Chiadi E. Ndumele, MD, PhD, an associate professor at Johns Hopkins Medicine in Baltimore and chair of the AHA’s recent presidential advisory on cardiovascular-kidney-metabolic health.

“Weight loss hasn’t been a central focus in our practice until recently, with the advent of these more powerful agents. There’s a need for more education around not only the use of these agents, but also around initiating weight loss discussions in a nonjudgmental way that reflects the complexity of obesity as a condition with multifactorial causes.”

The process will take time and may be similar to what happened with statins, he suggests. “Statins started in the endocrinology space, but as their cardiovascular benefits became more clear, they were increasingly adopted by cardiologists, primary care physicians, and others.”

Eugene Yang, MD, chair of the ACC Prevention of CVD Council and codirector of UW Medicine’s Cardiovascular Wellness and Prevention Program in Seattle, agrees that GLP-1 uptake by cardiologists will likely be slow. “It’s a bit premature to start prescribing right away,” he said. “Semaglutide hasn’t been approved for secondary prevention at this point, and until it’s approved specifically for that indication, I don’t think many cardiologists will prescribe it.”
 

Side Effects ‘Concerning’

Beyond the requisite approval, Dr. Yang is concerned about side effects such as gastroparesis, severe nausea, and vomiting. “I’m not sure cardiologists are going to feel comfortable helping patients deal with these effects.”

Because GLP-1 RAs are already being used widely in primary care, he says, “I personally would work in collaboration with either my primary care colleagues or with endocrinologists.”

Ambarish Pandey, MD, an associate professor of internal medicine (cardiology) and medical director of the heart failure with preserved ejection fraction (HFpEF) program at UT Southwestern Medical Center, Dallas, is already prescribing semaglutide to patients with HFpEF and obesity. “In terms of side effects, I just tell patients what to expect,” he says.

Dr. Pandey prepares patients for appetite reduction, early satiety and fullness, abdominal discomfort, nausea, and other gastrointestinal symptoms. “Then I start low and slowly titrate to achieve enough weight loss. If they’re having adverse effects on a higher dose, I use a lower dose.”

The approach is working well for most patients, he says. “Obviously there’s some initial getting used to the drug, but once that has happened, patients like it because they see improvements in their exercise capacity and quality of life.”

But GLP-1 RAs are also associated with increased heart rate, which “is never good news,” notes Howard Weintraub, MD, a professor of medicine at NYU Grossman School of Medicine in New York City and clinical director of the NYU Center for the Prevention of Cardiovascular Disease. At least some of the elevation may be masked by beta-blocker use, he suggests. “The mechanism is not well elucidated, but it is something we’re going to need to keep an eye on, because we don’t want to get ambushed.”
 

Cost, Access ‘Significant Barriers’

All the cardiologists this news organization spoke with agreed that cost and access will be significant barriers to widespread prescribing, at least for now.

“Prescribing for individuals at very high cardiovascular risk will probably give a reasonable amount of bang for your buck. But individuals with more adverse social determinants of health, who are more likely to have challenges with obesity and related complications, are also least likely to be able to pay the exorbitant costs out of pocket. So, this is also an important health equity issue,” Dr. Ndumele says.

Furthermore, he adds, where GLP-1 RAs will fit for those with a lower absolute CVD risk “is still a clear question.”

“Access comes two ways,” Dr. Weintraub says. “One is the supply, which continues to be an issue. You can’t sell the drug if you don’t have it.”

The other access route is the insurance companies. “Will they throw down a gauntlet and make cardiologists prove that a patient failed other obesity drugs before they can prescribe a GLP-1 RA? Some of the old obesity drugs are not only unpleasant to use, but they’re ineffective and may have bad cardiac signals.”

If the new drugs are approved for secondary prevention, patients will want them and doctors will want them, he says. The demand will be “huge,” and it’s not clear how it will be handled.

Dr. Pandey agrees that getting the drug without “good insurance” to cover the cost is a big challenge. “ As more of these drugs become available, hopefully the cost will come down, and hopefully access will grow as companies are able to scale up production.”
 

Add-On or Substitute?

Anticipating approval, Dr. Yang says it’s not yet clear where the GLP-1 RAs stand among the various available cardiovascular therapies.

“Based on the results of SELECT, one could argue that maybe it’s more important to get the weight down and reduce blood pressure versus adding another cholesterol-lowering medication, for example, especially if a patient is already on a statin and ezetimibe. But maybe their low-density lipoprotein cholesterol is not exactly below the threshold of the current guideline. And maybe they’re overweight or prediabetic, and they can lose 10% or 15% of their body weight with a GLP-1 RA. You may have to pick and choose.”

That said, he adds, “Who’s going to be able to afford all of this? Some patients would be taking a PCSK9 inhibitor, bempedoic acid because their lipids are not optimized, then a GLP-1 receptor. Right there, we’re talking about at least $2000 a month for those three medications. That’s not feasible.”

“This is one of the things I’ve worried about, given all the drugs some of our patients are on,” Dr. Weintraub says. “The data on cholesterol-lowering drugs are so monumental, it’s hard to say you can do without it. The same is true of blood pressure-lowering medication. So to my mind, a GLP-1 RA is going to have to be an add-on.”

“The only good news is that unlike in the heart failure arena, patients are not paying for other drugs on top of it,” he says. “Statins, ACE inhibitors, ARBs, and beta-blockers are all generic; they’re not going to leave a huge hole in the patient’s pocket when the donut hole [Medicare payment gap] comes around. So in this case, if the GLP-1 RAs get included, which I hope they will, the added cost may not be that horrible.”
 

What About Lifestyle Changes?

Everyone agreed that the drugs are not a substitute for lifestyle changes.

“I have seen many patients who take these medications reach plateaus, and when discontinued, gain back the weight. I counsel patients to view the medication as an aid and not necessarily a magic wand,” Dr. Lohr says.

Dr. Ndumele agrees. “I advocate a lifestyle-first approach,” he says. “I imagine there will be busy clinicians who will prescribe medications as a first line, but that’s not going to be our most effective approach.”

The major challenge to such an approach, he says, is that lifestyle support has to be ongoing. “It’s not the kind of thing that just happens in a yearly doctor’s visit appointment, and it’s been under-supported in most coverage and reimbursement strategies.”

In his clinical practice, which includes ongoing support for lifestyle changes, Dr. Ndumele is seeing far greater weight loss than was shown in SELECT. “I think there’s a real benefit to having the two approaches come together,” he says.

Dr. Yang also favors an emphasis on lifestyle. “The success rate of a lifestyle approach may be low, but that doesn’t change the importance of it. We need to figure out better ways to do it.” Leveraging technology is one way, he suggests, such as cellphone reminders to walk more or alerts to tell you when to sleep.

“I also encourage patients to monitor their own blood pressure, and they do.” Dr. Yang acknowledges that his patient population is highly educated with access to resources to purchase the technological devices. However, he adds, “if the clinician is negative, and doesn’t really believe these interventions will work, the patient can sense that, and then they won’t work.” It’s up to the clinician to promote the importance of these lifestyle changes in order to be successful. Is it discouraging at times? Yes. But don’t let the patient know.”

Dr. Pandey approaches the issue differently. “Our healthcare system is such that patients don’t get to see us that often, so I think we should start the lifestyle intervention, but also start the medication at the same time, in parallel, because we don’t have time to take a stepwise approach.”

“Lifestyle interventions are better received if patients see positive improvements, and the medication actually induces a positive improvement,” he says. He is concerned that if a lifestyle first approach doesn’t work “that can affect the willingness to try future therapies. And we don’t want to lose like 6 or 8 months just trying lifestyle when they could have benefited from the weight-loss medication, as well.”

Dr. Lohr, Dr. Ndumele, and Dr. Yang report no conflicts of interest. Dr. Weintraub reports being an investigator in the SELECT trial and a consultant for NovoNordisk. Dr. Pandey reports receiving research support from the National Institutes of Health; grant funding from Applied Therapeutics and Gilead Sciences; honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon therapies, Medtronic, Edwards Lifesciences, Science 37 Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, Emmi Solutions; and has received nonfinancial support from Pfizer and Merck; and serving as a consultant for Palomarin Inc. with stocks compensation.

A version of this article appeared on Medscape.com.

The positive results from the SELECT trial for the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were hailed as ushering in a “new era for patients with obesity.” In the trial of overweight and obese patients with cardiovascular disease (CVD), but no diabetes, semaglutide showed meaningful reductions in cardiovascular death, myocardial infarction, and stroke compared with placebo.

“I definitely see increasing adoption of GLP-1 RAs by cardiologists and expect the number to increase now that the data support its use in secondary prevention,” said Nicole L. Lohr, MD, PhD, chair of the American College of Cardiology (ACC) Board of Governors, and Mary G. Waters, chair of cardiovascular medicine at UAB, Birmingham.

But many cardiologists are more hesitant. “I think there’s going to be an increasing urgency for cardiologists to start prescribing these drugs, but I don’t think the comfort to do so is that widespread at this point,” said American Heart Association (AHA) volunteer Chiadi E. Ndumele, MD, PhD, an associate professor at Johns Hopkins Medicine in Baltimore and chair of the AHA’s recent presidential advisory on cardiovascular-kidney-metabolic health.

“Weight loss hasn’t been a central focus in our practice until recently, with the advent of these more powerful agents. There’s a need for more education around not only the use of these agents, but also around initiating weight loss discussions in a nonjudgmental way that reflects the complexity of obesity as a condition with multifactorial causes.”

The process will take time and may be similar to what happened with statins, he suggests. “Statins started in the endocrinology space, but as their cardiovascular benefits became more clear, they were increasingly adopted by cardiologists, primary care physicians, and others.”

Eugene Yang, MD, chair of the ACC Prevention of CVD Council and codirector of UW Medicine’s Cardiovascular Wellness and Prevention Program in Seattle, agrees that GLP-1 uptake by cardiologists will likely be slow. “It’s a bit premature to start prescribing right away,” he said. “Semaglutide hasn’t been approved for secondary prevention at this point, and until it’s approved specifically for that indication, I don’t think many cardiologists will prescribe it.”
 

Side Effects ‘Concerning’

Beyond the requisite approval, Dr. Yang is concerned about side effects such as gastroparesis, severe nausea, and vomiting. “I’m not sure cardiologists are going to feel comfortable helping patients deal with these effects.”

Because GLP-1 RAs are already being used widely in primary care, he says, “I personally would work in collaboration with either my primary care colleagues or with endocrinologists.”

Ambarish Pandey, MD, an associate professor of internal medicine (cardiology) and medical director of the heart failure with preserved ejection fraction (HFpEF) program at UT Southwestern Medical Center, Dallas, is already prescribing semaglutide to patients with HFpEF and obesity. “In terms of side effects, I just tell patients what to expect,” he says.

Dr. Pandey prepares patients for appetite reduction, early satiety and fullness, abdominal discomfort, nausea, and other gastrointestinal symptoms. “Then I start low and slowly titrate to achieve enough weight loss. If they’re having adverse effects on a higher dose, I use a lower dose.”

The approach is working well for most patients, he says. “Obviously there’s some initial getting used to the drug, but once that has happened, patients like it because they see improvements in their exercise capacity and quality of life.”

But GLP-1 RAs are also associated with increased heart rate, which “is never good news,” notes Howard Weintraub, MD, a professor of medicine at NYU Grossman School of Medicine in New York City and clinical director of the NYU Center for the Prevention of Cardiovascular Disease. At least some of the elevation may be masked by beta-blocker use, he suggests. “The mechanism is not well elucidated, but it is something we’re going to need to keep an eye on, because we don’t want to get ambushed.”
 

Cost, Access ‘Significant Barriers’

All the cardiologists this news organization spoke with agreed that cost and access will be significant barriers to widespread prescribing, at least for now.

“Prescribing for individuals at very high cardiovascular risk will probably give a reasonable amount of bang for your buck. But individuals with more adverse social determinants of health, who are more likely to have challenges with obesity and related complications, are also least likely to be able to pay the exorbitant costs out of pocket. So, this is also an important health equity issue,” Dr. Ndumele says.

Furthermore, he adds, where GLP-1 RAs will fit for those with a lower absolute CVD risk “is still a clear question.”

“Access comes two ways,” Dr. Weintraub says. “One is the supply, which continues to be an issue. You can’t sell the drug if you don’t have it.”

The other access route is the insurance companies. “Will they throw down a gauntlet and make cardiologists prove that a patient failed other obesity drugs before they can prescribe a GLP-1 RA? Some of the old obesity drugs are not only unpleasant to use, but they’re ineffective and may have bad cardiac signals.”

If the new drugs are approved for secondary prevention, patients will want them and doctors will want them, he says. The demand will be “huge,” and it’s not clear how it will be handled.

Dr. Pandey agrees that getting the drug without “good insurance” to cover the cost is a big challenge. “ As more of these drugs become available, hopefully the cost will come down, and hopefully access will grow as companies are able to scale up production.”
 

Add-On or Substitute?

Anticipating approval, Dr. Yang says it’s not yet clear where the GLP-1 RAs stand among the various available cardiovascular therapies.

“Based on the results of SELECT, one could argue that maybe it’s more important to get the weight down and reduce blood pressure versus adding another cholesterol-lowering medication, for example, especially if a patient is already on a statin and ezetimibe. But maybe their low-density lipoprotein cholesterol is not exactly below the threshold of the current guideline. And maybe they’re overweight or prediabetic, and they can lose 10% or 15% of their body weight with a GLP-1 RA. You may have to pick and choose.”

That said, he adds, “Who’s going to be able to afford all of this? Some patients would be taking a PCSK9 inhibitor, bempedoic acid because their lipids are not optimized, then a GLP-1 receptor. Right there, we’re talking about at least $2000 a month for those three medications. That’s not feasible.”

“This is one of the things I’ve worried about, given all the drugs some of our patients are on,” Dr. Weintraub says. “The data on cholesterol-lowering drugs are so monumental, it’s hard to say you can do without it. The same is true of blood pressure-lowering medication. So to my mind, a GLP-1 RA is going to have to be an add-on.”

“The only good news is that unlike in the heart failure arena, patients are not paying for other drugs on top of it,” he says. “Statins, ACE inhibitors, ARBs, and beta-blockers are all generic; they’re not going to leave a huge hole in the patient’s pocket when the donut hole [Medicare payment gap] comes around. So in this case, if the GLP-1 RAs get included, which I hope they will, the added cost may not be that horrible.”
 

What About Lifestyle Changes?

Everyone agreed that the drugs are not a substitute for lifestyle changes.

“I have seen many patients who take these medications reach plateaus, and when discontinued, gain back the weight. I counsel patients to view the medication as an aid and not necessarily a magic wand,” Dr. Lohr says.

Dr. Ndumele agrees. “I advocate a lifestyle-first approach,” he says. “I imagine there will be busy clinicians who will prescribe medications as a first line, but that’s not going to be our most effective approach.”

The major challenge to such an approach, he says, is that lifestyle support has to be ongoing. “It’s not the kind of thing that just happens in a yearly doctor’s visit appointment, and it’s been under-supported in most coverage and reimbursement strategies.”

In his clinical practice, which includes ongoing support for lifestyle changes, Dr. Ndumele is seeing far greater weight loss than was shown in SELECT. “I think there’s a real benefit to having the two approaches come together,” he says.

Dr. Yang also favors an emphasis on lifestyle. “The success rate of a lifestyle approach may be low, but that doesn’t change the importance of it. We need to figure out better ways to do it.” Leveraging technology is one way, he suggests, such as cellphone reminders to walk more or alerts to tell you when to sleep.

“I also encourage patients to monitor their own blood pressure, and they do.” Dr. Yang acknowledges that his patient population is highly educated with access to resources to purchase the technological devices. However, he adds, “if the clinician is negative, and doesn’t really believe these interventions will work, the patient can sense that, and then they won’t work.” It’s up to the clinician to promote the importance of these lifestyle changes in order to be successful. Is it discouraging at times? Yes. But don’t let the patient know.”

Dr. Pandey approaches the issue differently. “Our healthcare system is such that patients don’t get to see us that often, so I think we should start the lifestyle intervention, but also start the medication at the same time, in parallel, because we don’t have time to take a stepwise approach.”

“Lifestyle interventions are better received if patients see positive improvements, and the medication actually induces a positive improvement,” he says. He is concerned that if a lifestyle first approach doesn’t work “that can affect the willingness to try future therapies. And we don’t want to lose like 6 or 8 months just trying lifestyle when they could have benefited from the weight-loss medication, as well.”

Dr. Lohr, Dr. Ndumele, and Dr. Yang report no conflicts of interest. Dr. Weintraub reports being an investigator in the SELECT trial and a consultant for NovoNordisk. Dr. Pandey reports receiving research support from the National Institutes of Health; grant funding from Applied Therapeutics and Gilead Sciences; honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon therapies, Medtronic, Edwards Lifesciences, Science 37 Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, Emmi Solutions; and has received nonfinancial support from Pfizer and Merck; and serving as a consultant for Palomarin Inc. with stocks compensation.

A version of this article appeared on Medscape.com.

The positive results from the SELECT trial for the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were hailed as ushering in a “new era for patients with obesity.” In the trial of overweight and obese patients with cardiovascular disease (CVD), but no diabetes, semaglutide showed meaningful reductions in cardiovascular death, myocardial infarction, and stroke compared with placebo.

“I definitely see increasing adoption of GLP-1 RAs by cardiologists and expect the number to increase now that the data support its use in secondary prevention,” said Nicole L. Lohr, MD, PhD, chair of the American College of Cardiology (ACC) Board of Governors, and Mary G. Waters, chair of cardiovascular medicine at UAB, Birmingham.

But many cardiologists are more hesitant. “I think there’s going to be an increasing urgency for cardiologists to start prescribing these drugs, but I don’t think the comfort to do so is that widespread at this point,” said American Heart Association (AHA) volunteer Chiadi E. Ndumele, MD, PhD, an associate professor at Johns Hopkins Medicine in Baltimore and chair of the AHA’s recent presidential advisory on cardiovascular-kidney-metabolic health.

“Weight loss hasn’t been a central focus in our practice until recently, with the advent of these more powerful agents. There’s a need for more education around not only the use of these agents, but also around initiating weight loss discussions in a nonjudgmental way that reflects the complexity of obesity as a condition with multifactorial causes.”

The process will take time and may be similar to what happened with statins, he suggests. “Statins started in the endocrinology space, but as their cardiovascular benefits became more clear, they were increasingly adopted by cardiologists, primary care physicians, and others.”

Eugene Yang, MD, chair of the ACC Prevention of CVD Council and codirector of UW Medicine’s Cardiovascular Wellness and Prevention Program in Seattle, agrees that GLP-1 uptake by cardiologists will likely be slow. “It’s a bit premature to start prescribing right away,” he said. “Semaglutide hasn’t been approved for secondary prevention at this point, and until it’s approved specifically for that indication, I don’t think many cardiologists will prescribe it.”
 

Side Effects ‘Concerning’

Beyond the requisite approval, Dr. Yang is concerned about side effects such as gastroparesis, severe nausea, and vomiting. “I’m not sure cardiologists are going to feel comfortable helping patients deal with these effects.”

Because GLP-1 RAs are already being used widely in primary care, he says, “I personally would work in collaboration with either my primary care colleagues or with endocrinologists.”

Ambarish Pandey, MD, an associate professor of internal medicine (cardiology) and medical director of the heart failure with preserved ejection fraction (HFpEF) program at UT Southwestern Medical Center, Dallas, is already prescribing semaglutide to patients with HFpEF and obesity. “In terms of side effects, I just tell patients what to expect,” he says.

Dr. Pandey prepares patients for appetite reduction, early satiety and fullness, abdominal discomfort, nausea, and other gastrointestinal symptoms. “Then I start low and slowly titrate to achieve enough weight loss. If they’re having adverse effects on a higher dose, I use a lower dose.”

The approach is working well for most patients, he says. “Obviously there’s some initial getting used to the drug, but once that has happened, patients like it because they see improvements in their exercise capacity and quality of life.”

But GLP-1 RAs are also associated with increased heart rate, which “is never good news,” notes Howard Weintraub, MD, a professor of medicine at NYU Grossman School of Medicine in New York City and clinical director of the NYU Center for the Prevention of Cardiovascular Disease. At least some of the elevation may be masked by beta-blocker use, he suggests. “The mechanism is not well elucidated, but it is something we’re going to need to keep an eye on, because we don’t want to get ambushed.”
 

Cost, Access ‘Significant Barriers’

All the cardiologists this news organization spoke with agreed that cost and access will be significant barriers to widespread prescribing, at least for now.

“Prescribing for individuals at very high cardiovascular risk will probably give a reasonable amount of bang for your buck. But individuals with more adverse social determinants of health, who are more likely to have challenges with obesity and related complications, are also least likely to be able to pay the exorbitant costs out of pocket. So, this is also an important health equity issue,” Dr. Ndumele says.

Furthermore, he adds, where GLP-1 RAs will fit for those with a lower absolute CVD risk “is still a clear question.”

“Access comes two ways,” Dr. Weintraub says. “One is the supply, which continues to be an issue. You can’t sell the drug if you don’t have it.”

The other access route is the insurance companies. “Will they throw down a gauntlet and make cardiologists prove that a patient failed other obesity drugs before they can prescribe a GLP-1 RA? Some of the old obesity drugs are not only unpleasant to use, but they’re ineffective and may have bad cardiac signals.”

If the new drugs are approved for secondary prevention, patients will want them and doctors will want them, he says. The demand will be “huge,” and it’s not clear how it will be handled.

Dr. Pandey agrees that getting the drug without “good insurance” to cover the cost is a big challenge. “ As more of these drugs become available, hopefully the cost will come down, and hopefully access will grow as companies are able to scale up production.”
 

Add-On or Substitute?

Anticipating approval, Dr. Yang says it’s not yet clear where the GLP-1 RAs stand among the various available cardiovascular therapies.

“Based on the results of SELECT, one could argue that maybe it’s more important to get the weight down and reduce blood pressure versus adding another cholesterol-lowering medication, for example, especially if a patient is already on a statin and ezetimibe. But maybe their low-density lipoprotein cholesterol is not exactly below the threshold of the current guideline. And maybe they’re overweight or prediabetic, and they can lose 10% or 15% of their body weight with a GLP-1 RA. You may have to pick and choose.”

That said, he adds, “Who’s going to be able to afford all of this? Some patients would be taking a PCSK9 inhibitor, bempedoic acid because their lipids are not optimized, then a GLP-1 receptor. Right there, we’re talking about at least $2000 a month for those three medications. That’s not feasible.”

“This is one of the things I’ve worried about, given all the drugs some of our patients are on,” Dr. Weintraub says. “The data on cholesterol-lowering drugs are so monumental, it’s hard to say you can do without it. The same is true of blood pressure-lowering medication. So to my mind, a GLP-1 RA is going to have to be an add-on.”

“The only good news is that unlike in the heart failure arena, patients are not paying for other drugs on top of it,” he says. “Statins, ACE inhibitors, ARBs, and beta-blockers are all generic; they’re not going to leave a huge hole in the patient’s pocket when the donut hole [Medicare payment gap] comes around. So in this case, if the GLP-1 RAs get included, which I hope they will, the added cost may not be that horrible.”
 

What About Lifestyle Changes?

Everyone agreed that the drugs are not a substitute for lifestyle changes.

“I have seen many patients who take these medications reach plateaus, and when discontinued, gain back the weight. I counsel patients to view the medication as an aid and not necessarily a magic wand,” Dr. Lohr says.

Dr. Ndumele agrees. “I advocate a lifestyle-first approach,” he says. “I imagine there will be busy clinicians who will prescribe medications as a first line, but that’s not going to be our most effective approach.”

The major challenge to such an approach, he says, is that lifestyle support has to be ongoing. “It’s not the kind of thing that just happens in a yearly doctor’s visit appointment, and it’s been under-supported in most coverage and reimbursement strategies.”

In his clinical practice, which includes ongoing support for lifestyle changes, Dr. Ndumele is seeing far greater weight loss than was shown in SELECT. “I think there’s a real benefit to having the two approaches come together,” he says.

Dr. Yang also favors an emphasis on lifestyle. “The success rate of a lifestyle approach may be low, but that doesn’t change the importance of it. We need to figure out better ways to do it.” Leveraging technology is one way, he suggests, such as cellphone reminders to walk more or alerts to tell you when to sleep.

“I also encourage patients to monitor their own blood pressure, and they do.” Dr. Yang acknowledges that his patient population is highly educated with access to resources to purchase the technological devices. However, he adds, “if the clinician is negative, and doesn’t really believe these interventions will work, the patient can sense that, and then they won’t work.” It’s up to the clinician to promote the importance of these lifestyle changes in order to be successful. Is it discouraging at times? Yes. But don’t let the patient know.”

Dr. Pandey approaches the issue differently. “Our healthcare system is such that patients don’t get to see us that often, so I think we should start the lifestyle intervention, but also start the medication at the same time, in parallel, because we don’t have time to take a stepwise approach.”

“Lifestyle interventions are better received if patients see positive improvements, and the medication actually induces a positive improvement,” he says. He is concerned that if a lifestyle first approach doesn’t work “that can affect the willingness to try future therapies. And we don’t want to lose like 6 or 8 months just trying lifestyle when they could have benefited from the weight-loss medication, as well.”

Dr. Lohr, Dr. Ndumele, and Dr. Yang report no conflicts of interest. Dr. Weintraub reports being an investigator in the SELECT trial and a consultant for NovoNordisk. Dr. Pandey reports receiving research support from the National Institutes of Health; grant funding from Applied Therapeutics and Gilead Sciences; honoraria outside of the present study as an advisor/consultant for Tricog Health Inc, Lilly USA, Rivus, Cytokinetics, Roche Diagnostics, Axon therapies, Medtronic, Edwards Lifesciences, Science 37 Novo Nordisk, Bayer, Merck, Sarfez Pharmaceuticals, Emmi Solutions; and has received nonfinancial support from Pfizer and Merck; and serving as a consultant for Palomarin Inc. with stocks compensation.

A version of this article appeared on Medscape.com.

In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
 

Good vs. bad PA

“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.

The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.

In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
 

Lack of autonomy

Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.

“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”

Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.

Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.

“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.

“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.

Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
 

Research gaps

However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.

“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.

Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.

“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.

However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
 

Health inequity issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”

Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”

Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
 

A version of this article first appeared on Medscape.com.

In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
 

Good vs. bad PA

“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.

The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.

In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
 

Lack of autonomy

Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.

“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”

Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.

Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.

“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.

“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.

Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
 

Research gaps

However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.

“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.

Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.

“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.

However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
 

Health inequity issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”

Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”

Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
 

A version of this article first appeared on Medscape.com.

In the pursuit of optimal health, regular physical activity (PA) is recommended to protect against dementia, cardiovascular disease (CVD), cancer, and other noncommunicable diseases. A significant body of research suggests the benefits of PA are positively correlated with higher frequency and intensity – with more often deemed better. This research has spawned a focus on increasing step counts and investing in standing desks and other interventions aimed at keeping people active.

But for many people, PA is a work requirement over which they have little control, and emerging evidence suggests that these workers not only do not reap the benefits associated with leisure-time PA, but they also actually experience an increased risk for the very conditions that PA is intended to prevent.

A study published recently in The Lancet Regional Health – Europe used registry data from more than 7,000 adults in Norway, following them from age 33 to 65 years, to assess PA trajectories and risks for later-life mild cognitive impairment (MCI) and dementia at age 70 or older.

“Incorporating a life-course perspective gives a broader picture of how participants’ occupational histories relate to cognitive impairment later in life,” principal investigator Vegard Skirbekk, PhD, Columbia University Mailman School of Public Health, New York, said in an interview. Other studies typically have assessed occupational PA at a single time point, often close to the end of an individual’s career, and largely relied on self-report, he said.

Study participants worked in more than 300 different occupations. General physical activities performed on the included jobs required “considerable” use of arms and legs and moving the whole body, such as climbing, lifting, balancing, walking, stooping, and handling of materials.

Dr. Skirbekk and colleagues grouped participants into four PA trajectories over the 44-year study period: stable low, increasing then decreasing, stable intermediate, and stable high.

A total of 902 individuals were diagnosed with dementia and 2,407 with MCI at age 70 years or older. After adjustment, risks for MCI and dementia were 15.5% for those with higher occupational PA scores in the latter part of their working life and 9% for those with lower physical demands. The researchers concluded that “consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment.”

The findings support those of the Copenhagen Male Study. Published in 2020, this longitudinal study compared leisure-time and occupational PA among more than 4,000 men in Denmark aged 40-59 at baseline in 1970-1971 and followed them until they turned 60. After adjustment, participants with high occupational PA had a 55% greater risk of developing dementia compared with those doing sedentary work.
 

Good vs. bad PA

“[T]he WHO [World Health Organization] guide to preventing dementia and disease on the whole mentions physical activity as an important factor. But our study suggests that it must be a ‘good’ form of physical activity, which hard physical work is not,” said Kirsten Nabe-Nielsen, PhD, lead author of this study

Beyond dementia, another recent study adds to a wealth of data on associations between occupational PA and cardiovascular risks. The cross-sectional analysis of U.S. data from the National Institute for Occupational Safety and Health showed that odds of CVD were higher when participants were “always” performing total occupational activity (odds ratio [OR], 1.99), occupational exertion (OR, 2.15), or occupational standing and walking around (OR, 1.84) compared with “never” engaging in these activities.

The contrasting effects of leisure-time vs. occupational PA constitute the “physical activity paradox” hypothesis. Starting in 2011, multiple studies by Andreas Holtermann, PhD, of the National Research Centre for the Working Environment lend support to the PA paradox theory, as do subsequent studies by others.

Although only “marginally considered” until a few years ago, recent large cohort studies seem to confirm the paradox, Pier Luigi Temporelli, MD wrote in a recent editorial.

In separate interviews, Dr. Skirbekk and lead author Tyler Quinn, PhD, MS, West Virginia University, Morgantown, pointed to the PA paradox as an explanation for their own recent findings, suggesting that the mechanisms that underlie it probably are responsible for the associated deleterious effects of occupational PA on the brain and heart, and even mortality.

“It’s well established that PA in your leisure time can be positive, but in the workplace, the results are quite the opposite,” Dr. Skirbekk said. “The specific mechanisms for why occupational PA is associated with elevated dementia risk are still not well understood and we need more knowledge. But we know that higher occupational physical demands have been linked to smaller hippocampal volume and poorer memory performance.”

Furthermore, he said, individuals working in jobs with high demands, both psychological and physical, combined with low job control perform more poorly on cognitive testing later in life.

“We looked mainly at professions where people have heavy workloads and you have much less autonomy, such as nursing assistants, office cleaners, childcare workers, and other personal care workers,” he said. “You cannot sit. You have somebody relying on you. It’s not all pleasure, and it can be very hard. That’s where we find the associations.”
 

Lack of autonomy

Specific characteristics indirectly associated with high occupational PA jobs – low cognitive stimuli, lifestyle factors, and socioeconomic influences – as well as factors directly related to high occupational PA, such as long hours, repetitive tasks, low levels of control, and stress, could also adversely affect cognitive trajectories, Dr. Skirbekk explained.

“By contrast, leisure-time physical activities tend to be of much shorter duration; are associated with socialization, play, [and] positive emotions; and [include] the opportunity to take breaks or shift to other types of activities if one prefers,” he said. “It may also be that too little or too much PA could be adversely related to cognitive outcomes – hence moderate activity levels, for example 10,000 steps a day, are still likely beneficial for cognitive functioning.”

Dr. Quinn said most of the CVD risk linked to occupational PA has to do with long periods of exertion such as lifting and carrying objects. While occupational standing and walking all day are also linked to CVD risk, they’re not as risky as lifting and carrying, he said.

Like Dr. Skirbekk, Dr. Quinn noted that individuals can take a break from leisure-time PA when they are tired, but occupational PA doesn’t have that same autonomy to allow for recovery.

“So, in many cases, individuals are not getting the recovery their body needs to actually experience PA benefits, because those benefits come during rest,” Dr. Quinn said.

“We’ve shown that PA at work raises acute cardiovascular responses, which are related to cardiovascular risk. For example, 24-hour and waking heart rate and diastolic blood pressure, as well as nonwork diastolic blood pressure, all were significantly higher on workdays versus non-workdays,” he said.

Dr. Quinn also said that psychological stress at work amplifies risk. “A person who does PA at work and is stressed is likely to be at greater risk than someone who has a physically active job but doesn’t have psychological stress combined with it.”
 

Research gaps

However, Dr. Skirbekk noted that there are strategies that can reduce the risk for MCI and dementia despite high levels of occupational PA. “It is often difficult to change professions, and even if you do, it won’t immediately affect cognition. But altering one’s lifestyle is likely to have effects on cognitive development across the life cycle.

“Many clinicians say they always advise lifestyle changes, but nothing happens. But it makes sense to emphasize that these changes – stopping smoking, eating well, getting proper sleep, etc. – affect not only cardiovascular risk but also cognition. And I think clinicians should also take a patient’s occupation into account during any evaluation,” Dr. Skirbekk noted.

Dr. Quinn said it isn’t realistic to expect workers to come up with solutions to the PA paradox because many don’t have the autonomy to be able to mitigate their occupational risk.

“I think administrative controls and policy changes eventually will be the levers of change. We’re not quite there yet, but those are the types of things we should do when we’re trying to reduce loads in some way, or reduce the time that people spend doing certain tasks we know are potentially bad,” he said.

However, not everyone agrees that occupational PA doesn’t confer the same benefits of leisure-time PA, at least with respect to cardiovascular risk. For example, the Prospective Urban Rural Epidemiology (PURE) study, which includes a cohort of 130,000 people from 17 high-income, middle-income, and low-income countries, concluded that both higher recreational and nonrecreational PA were associated with a lower risk for mortality and CVD events.

What additional research is needed to clarify the effects of occupational and leisure-time activity and to address conflicting findings?

“Even studies coming out now regarding the effects of occupational PA have mainly used older data,” Dr. Skirbekk noted. “Labor markets and job demands have changed over time. There are different types of tasks and skills required now than there were 20 or 40 years ago. And of course, working from home is a recent phenomenon that’s happened on a large scale and might affect daily routines, sleep patterns, and also cognition. We need a better understanding of what the consequences might be.”
 

Health inequity issue

More research is also necessary to understand the social determinants of cognitive decline, impairment, and dementia, he said. “Many of the studies we see today are based on self-report of what someone has done in the past, which is particularly problematic for individuals who are impaired or who give interviews with others, which can induce biases.”

Dr. Quinn suggests that PA guidelines may need to differentiate between occupational and leisure-time PA to better reflect current research findings.

Meanwhile, Dr. Skirbekk and Dr. Quinn both point to the toll that occupational PA takes on the brain and body in lower-income workers as an important health equity issue.

“Our national guidelines for PA include occupational activity,” said Dr. Quinn. “But it’s clear that a lot of people who are getting a lot of occupational PA, particularly socioeconomic and racial/ethnic minorities, are not benefiting from it.”

Dr. Holtermann, who has arguably done the most research to date on the PA paradox, noted in a recent editorial that the majority of workers with high occupational PA have a low socioeconomic position and therefore “improving our understanding of the underlying mechanisms behind the PA health paradox and identifying new intervention targets along those pathways will be an important step to reduce socioeconomic health inequalities across the globe.”
 

A version of this article first appeared on Medscape.com.

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Maternal depressive symptoms probably start at or before pregnancy, with trajectories that remain stable across the perinatal into the postnatal period, new research suggests.

The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.

The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore. 

“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”

This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
 

Start screening sooner 

The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian. 

The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).

The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.

“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”

The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”

Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception. 

“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.” 
 

Depression is likely worse in the United States

Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”

John Abbott/Columbia University

Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”

“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded. 

This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.

A version of this article appeared on Medscape.com.

Maternal depressive symptoms probably start at or before pregnancy, with trajectories that remain stable across the perinatal into the postnatal period, new research suggests.

The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.

The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore. 

“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”

This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
 

Start screening sooner 

The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian. 

The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).

The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.

“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”

The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”

Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception. 

“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.” 
 

Depression is likely worse in the United States

Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”

John Abbott/Columbia University

Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”

“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded. 

This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.

A version of this article appeared on Medscape.com.

Maternal depressive symptoms probably start at or before pregnancy, with trajectories that remain stable across the perinatal into the postnatal period, new research suggests.

The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.

The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore. 

“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”

This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
 

Start screening sooner 

The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian. 

The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).

The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.

“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”

The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”

Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception. 

“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.” 
 

Depression is likely worse in the United States

Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”

John Abbott/Columbia University

Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”

“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded. 

This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Irritable bowel syndrome (IBS) is associated with increased odds of fibromyalgia and chronic fatigue syndrome (CFS), new research suggests.

METHODOLOGY:

• The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
• The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
• A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
• Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).

TAKEAWAY:

• Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
• The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
• IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
• Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
• Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.

IN PRACTICE:

“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.

SOURCE:

Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.

LIMITATIONS:

The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.

DISCLOSURES:

The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

TOPLINE:

Irritable bowel syndrome (IBS) is associated with increased odds of fibromyalgia and chronic fatigue syndrome (CFS), new research suggests.

METHODOLOGY:

• The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
• The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
• A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
• Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).

TAKEAWAY:

• Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
• The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
• IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
• Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
• Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.

IN PRACTICE:

“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.

SOURCE:

Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.

LIMITATIONS:

The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.

DISCLOSURES:

The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

TOPLINE:

Irritable bowel syndrome (IBS) is associated with increased odds of fibromyalgia and chronic fatigue syndrome (CFS), new research suggests.

METHODOLOGY:

• The authors conducted a retrospective cohort study to investigate the prevalence and predictors of fibromyalgia and CFS in patients hospitalized with IBS vs people without IBS.
• The researchers used ICD-10 codes to analyze U.S. National Inpatient Sample (NIS) data from 2016-2019.
• A subgroup analysis investigated associations with IBS-diarrhea (IBS-D), IBS-constipation (IBS-C), and IBS-mixed types.
• Variables included patient age, sex, ethnicity, race, household income, insurance status, and hospital-level characteristics (including location, bed size, and teaching status).

TAKEAWAY:

• Among 1.2 million patients with IBS included in the study, 10.7% also had fibromyalgia and 0.4% had CFS. The majority of fibromyalgia (96.5%) and CFS (89.9%) patients were female and White (86.5%). CFS prevalence also was highest among White persons (90.7%).
• The prevalence of fibromyalgia and CFS was significantly higher in patients with IBS compared to those without IBS (adjusted odds ratio [AOR], 5.33 for fibromyalgia and AOR, 5.4 for CFS).
• IBS-D, IBS-C, and IBS-mixed types were independently associated with increased odds of fibromyalgia and CFS.
• Independent predictors of increased odds of fibromyalgia and CFS, respectively, were increasing age (AOR, 1.02 for both), female sex (AOR, 11.2; AOR, 1.86) and White race (AOR, 2.04; AOR, 1.69).
• Overall, White race, lower socioeconomic status, smoking, alcohol use, obesity, and hyperlipidemia were associated with increased odds of fibromyalgia. For CFS, increased odds were associated with White race, higher socioeconomic status, smoking, obesity, and hyperlipidemia.

IN PRACTICE:

“In current clinical practice, there is a high risk of neglecting multi-syndromic patients. We as clinicians should integrate in our practice with regular screening for other somatic disorders in the IBS population and determine the need to consult other specialties like rheumatology and psychiatry to improve the overall health outcome in IBS patients,” the authors wrote.

SOURCE:

Zahid Ijaz Tarar, MD, University of Missouri, Columbia, led the study, which was published online in Biomedicines.

LIMITATIONS:

The retrospective design of the study can only show associations, not a causal relationship. Lack of blinding and randomization in the data creates bias. The NIS database does not provide medication and laboratory data, so the effect of pharmaceutical therapies cannot be measured.

DISCLOSURES:

The research received no external funding. The authors declare no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

Two biomarkers – pregnancy-associated plasma protein A2 (PAPP-A2) and activin A – when added to relevant clinical information have a better positive predictive value than and a comparable negative predictive value to the currently used ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF), new research suggests.

The third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia. By contrast, PAPP-A2 and activin A could serve as biomarkers to predict the occurrence as well as the absence of preeclampsia, according to the authors.

Preeclampsia has “potentially devastating maternal and fetal complications, [including] significantly increased cardiovascular risk for affected women later in life,” study author Stella S. Daskalopoulou, MD, PhD, associate professor of medicine at McGill University Health Centre in Montreal, said in an interview.

“A more accurate prediction of preeclampsia is expected to improve risk stratification and clinical care and shape clinical practice guidelines,” she said.

The study was published online in the Canadian Journal of Cardiology.
 

Better predictive value

For a prospective cohort study, the investigators recruited 192 women with first-trimester high-risk singleton pregnancies from tertiary obstetric clinics in Montreal.

At baseline, they collected clinical information, including height, prepregnancy weight, personal and family medical history, and medication use.

At each trimester, blood pressure was measured, and blood samples were collected to quantify sFlt-1, PlGF, PAPP-A2, PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. For the sFlt-1:PlGF ratio, the researchers used a cutoff point of 38, based on prior evidence. Because there are no agreed-upon cutoff points for the other biomarkers, they chose cutoff points that maximized sensitivity and specificity.

Pregnancies were considered high risk if the mother had any of the following conditions: prepregnancy BMI ≥ 25, maternal age ≥ 35 years, chronic hypertension, diabetes, renal disease, conception via in vitro fertilization, or maternal or first-degree family history of preeclampsia.

The primary outcome was preeclampsia, which was defined according to the Society of Obstetrics and Gynecology guidelines as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure of ≥ mm Hg together with either proteinuria or maternal end-organ dysfunction.

A total of 18 women (9.38%) developed preeclampsia. Those women had higher blood pressure at baseline (although it was within normal limits) and were more likely to have preexisting diabetes or a previous pregnancy with preeclampsia. They were also more likely to report Black race. Serum levels of PAPP-A, PAPP-A2, activin A, and inhibin A were significantly different between patients who developed preeclampsia and those who did not. These levels were increased throughout pregnancy.

Alongside the sFlt-1:PlGF ratio, two biomarkers, PAPP-A2 (odds ratio, 1.78) and activin A (OR, 1.84), were significantly associated with the primary outcome after adjustment for age, prepregnancy BMI, race, and mean arterial pressure.

When added to a model that included those clinical factors, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% vs. 66.67%). The two biomarkers also had a negative predictive value that was comparable to that of the sFlt-1:PlGF ratio (97.69% vs. 96%).

Study limitations include the small sample size and missing covariates for some participants. Furthermore, the findings cannot be generalized to low-risk populations.

“Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and thus could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies,” the authors concluded.

Dr. Daskalopoulou said that her group is currently performing a large multinational study, PULSE, “which will be the ideal platform to validate and extend our findings. The aim of the study is to predict preeclampsia using a multimodal approach that includes arterial stiffness measurements and blood biomarkers.”

She expanded on the potential benefits of this research. “Finding an accurate predictive tool would not only help design appropriate early care plans for truly high-risk pregnant women, including monitoring and delivery planning, but also facilitate the development of novel strategies for the prevention and treatment of preeclampsia, improving the life of millions of young mothers and their offspring around the world.”
 

Promising biomarkers

Commenting on the study, Nieca Goldberg, MD, clinical associate professor of medicine at NYU Langone Health and medical director of Atria, both in New York, said, “These biomarkers are promising, as the current biomarker, sFlt-1:PlGF, is good at ruling out preeclampsia in the short term, while the new biomarkers show that they are better at ruling in preeclampsia” as well as ruling it out. Dr. Goldberg was not involved in the research.

“The current study is small, some participant data points are missing, and the researchers only studied high-risk pregnancies,” she added. “We need larger studies of all the risk markers, in both high- and low-risk pregnancies that are followed throughout pregnancy.”

This work was supported by the Fonds de recherche du Québec Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women›s Health. Dr. Daskalopoulou is a senior clinician-scientist supported by a FRQS Clinician Scientist-Senior salary award. Dr. Daskalopoulou and Dr. Goldberg disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

Two biomarkers – pregnancy-associated plasma protein A2 (PAPP-A2) and activin A – when added to relevant clinical information have a better positive predictive value than and a comparable negative predictive value to the currently used ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF), new research suggests.

The third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia. By contrast, PAPP-A2 and activin A could serve as biomarkers to predict the occurrence as well as the absence of preeclampsia, according to the authors.

Preeclampsia has “potentially devastating maternal and fetal complications, [including] significantly increased cardiovascular risk for affected women later in life,” study author Stella S. Daskalopoulou, MD, PhD, associate professor of medicine at McGill University Health Centre in Montreal, said in an interview.

“A more accurate prediction of preeclampsia is expected to improve risk stratification and clinical care and shape clinical practice guidelines,” she said.

The study was published online in the Canadian Journal of Cardiology.
 

Better predictive value

For a prospective cohort study, the investigators recruited 192 women with first-trimester high-risk singleton pregnancies from tertiary obstetric clinics in Montreal.

At baseline, they collected clinical information, including height, prepregnancy weight, personal and family medical history, and medication use.

At each trimester, blood pressure was measured, and blood samples were collected to quantify sFlt-1, PlGF, PAPP-A2, PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. For the sFlt-1:PlGF ratio, the researchers used a cutoff point of 38, based on prior evidence. Because there are no agreed-upon cutoff points for the other biomarkers, they chose cutoff points that maximized sensitivity and specificity.

Pregnancies were considered high risk if the mother had any of the following conditions: prepregnancy BMI ≥ 25, maternal age ≥ 35 years, chronic hypertension, diabetes, renal disease, conception via in vitro fertilization, or maternal or first-degree family history of preeclampsia.

The primary outcome was preeclampsia, which was defined according to the Society of Obstetrics and Gynecology guidelines as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure of ≥ mm Hg together with either proteinuria or maternal end-organ dysfunction.

A total of 18 women (9.38%) developed preeclampsia. Those women had higher blood pressure at baseline (although it was within normal limits) and were more likely to have preexisting diabetes or a previous pregnancy with preeclampsia. They were also more likely to report Black race. Serum levels of PAPP-A, PAPP-A2, activin A, and inhibin A were significantly different between patients who developed preeclampsia and those who did not. These levels were increased throughout pregnancy.

Alongside the sFlt-1:PlGF ratio, two biomarkers, PAPP-A2 (odds ratio, 1.78) and activin A (OR, 1.84), were significantly associated with the primary outcome after adjustment for age, prepregnancy BMI, race, and mean arterial pressure.

When added to a model that included those clinical factors, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% vs. 66.67%). The two biomarkers also had a negative predictive value that was comparable to that of the sFlt-1:PlGF ratio (97.69% vs. 96%).

Study limitations include the small sample size and missing covariates for some participants. Furthermore, the findings cannot be generalized to low-risk populations.

“Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and thus could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies,” the authors concluded.

Dr. Daskalopoulou said that her group is currently performing a large multinational study, PULSE, “which will be the ideal platform to validate and extend our findings. The aim of the study is to predict preeclampsia using a multimodal approach that includes arterial stiffness measurements and blood biomarkers.”

She expanded on the potential benefits of this research. “Finding an accurate predictive tool would not only help design appropriate early care plans for truly high-risk pregnant women, including monitoring and delivery planning, but also facilitate the development of novel strategies for the prevention and treatment of preeclampsia, improving the life of millions of young mothers and their offspring around the world.”
 

Promising biomarkers

Commenting on the study, Nieca Goldberg, MD, clinical associate professor of medicine at NYU Langone Health and medical director of Atria, both in New York, said, “These biomarkers are promising, as the current biomarker, sFlt-1:PlGF, is good at ruling out preeclampsia in the short term, while the new biomarkers show that they are better at ruling in preeclampsia” as well as ruling it out. Dr. Goldberg was not involved in the research.

“The current study is small, some participant data points are missing, and the researchers only studied high-risk pregnancies,” she added. “We need larger studies of all the risk markers, in both high- and low-risk pregnancies that are followed throughout pregnancy.”

This work was supported by the Fonds de recherche du Québec Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women›s Health. Dr. Daskalopoulou is a senior clinician-scientist supported by a FRQS Clinician Scientist-Senior salary award. Dr. Daskalopoulou and Dr. Goldberg disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

Two biomarkers – pregnancy-associated plasma protein A2 (PAPP-A2) and activin A – when added to relevant clinical information have a better positive predictive value than and a comparable negative predictive value to the currently used ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF), new research suggests.

The third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia. By contrast, PAPP-A2 and activin A could serve as biomarkers to predict the occurrence as well as the absence of preeclampsia, according to the authors.

Preeclampsia has “potentially devastating maternal and fetal complications, [including] significantly increased cardiovascular risk for affected women later in life,” study author Stella S. Daskalopoulou, MD, PhD, associate professor of medicine at McGill University Health Centre in Montreal, said in an interview.

“A more accurate prediction of preeclampsia is expected to improve risk stratification and clinical care and shape clinical practice guidelines,” she said.

The study was published online in the Canadian Journal of Cardiology.
 

Better predictive value

For a prospective cohort study, the investigators recruited 192 women with first-trimester high-risk singleton pregnancies from tertiary obstetric clinics in Montreal.

At baseline, they collected clinical information, including height, prepregnancy weight, personal and family medical history, and medication use.

At each trimester, blood pressure was measured, and blood samples were collected to quantify sFlt-1, PlGF, PAPP-A2, PAPP-A, activin A, inhibin A, follistatin, and glycosylated fibronectin. For the sFlt-1:PlGF ratio, the researchers used a cutoff point of 38, based on prior evidence. Because there are no agreed-upon cutoff points for the other biomarkers, they chose cutoff points that maximized sensitivity and specificity.

Pregnancies were considered high risk if the mother had any of the following conditions: prepregnancy BMI ≥ 25, maternal age ≥ 35 years, chronic hypertension, diabetes, renal disease, conception via in vitro fertilization, or maternal or first-degree family history of preeclampsia.

The primary outcome was preeclampsia, which was defined according to the Society of Obstetrics and Gynecology guidelines as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure of ≥ mm Hg together with either proteinuria or maternal end-organ dysfunction.

A total of 18 women (9.38%) developed preeclampsia. Those women had higher blood pressure at baseline (although it was within normal limits) and were more likely to have preexisting diabetes or a previous pregnancy with preeclampsia. They were also more likely to report Black race. Serum levels of PAPP-A, PAPP-A2, activin A, and inhibin A were significantly different between patients who developed preeclampsia and those who did not. These levels were increased throughout pregnancy.

Alongside the sFlt-1:PlGF ratio, two biomarkers, PAPP-A2 (odds ratio, 1.78) and activin A (OR, 1.84), were significantly associated with the primary outcome after adjustment for age, prepregnancy BMI, race, and mean arterial pressure.

When added to a model that included those clinical factors, a positive third-trimester result for both PAPP-A2 and activin A had a better positive predictive value than the sFlt-1:PlGF ratio added to the clinical model (91.67% vs. 66.67%). The two biomarkers also had a negative predictive value that was comparable to that of the sFlt-1:PlGF ratio (97.69% vs. 96%).

Study limitations include the small sample size and missing covariates for some participants. Furthermore, the findings cannot be generalized to low-risk populations.

“Whereas the third-trimester sFlt-1:PlGF ratio can predict short-term absence of preeclampsia, PAPP-A2 and activin A had both high positive and negative predictive values and thus could serve as biomarkers to predict the occurrence (and absence) of preeclampsia; these findings will be validated in future studies,” the authors concluded.

Dr. Daskalopoulou said that her group is currently performing a large multinational study, PULSE, “which will be the ideal platform to validate and extend our findings. The aim of the study is to predict preeclampsia using a multimodal approach that includes arterial stiffness measurements and blood biomarkers.”

She expanded on the potential benefits of this research. “Finding an accurate predictive tool would not only help design appropriate early care plans for truly high-risk pregnant women, including monitoring and delivery planning, but also facilitate the development of novel strategies for the prevention and treatment of preeclampsia, improving the life of millions of young mothers and their offspring around the world.”
 

Promising biomarkers

Commenting on the study, Nieca Goldberg, MD, clinical associate professor of medicine at NYU Langone Health and medical director of Atria, both in New York, said, “These biomarkers are promising, as the current biomarker, sFlt-1:PlGF, is good at ruling out preeclampsia in the short term, while the new biomarkers show that they are better at ruling in preeclampsia” as well as ruling it out. Dr. Goldberg was not involved in the research.

“The current study is small, some participant data points are missing, and the researchers only studied high-risk pregnancies,” she added. “We need larger studies of all the risk markers, in both high- and low-risk pregnancies that are followed throughout pregnancy.”

This work was supported by the Fonds de recherche du Québec Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women›s Health. Dr. Daskalopoulou is a senior clinician-scientist supported by a FRQS Clinician Scientist-Senior salary award. Dr. Daskalopoulou and Dr. Goldberg disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

Lawrence Faucette, the 58-year-old man with terminal heart disease who received the world’s second genetically modified pig heart transplant, died on Oct. 30, 2023, the University of Maryland Medical Center (UMMC), Baltimore, reported in a statement.

Mr. Faucette, a former lab tech who was turned down repeatedly for a standard allograft transplantation because of his various medical conditions, received the pig heart transplant on Sept. 20, 2023.

He first came to UMMC as a patient on Sept. 14. When he was admitted, he was in end-stage heart failure. Shortly before the surgery, his heart stopped, and he required resuscitation.

On Sept. 15, the Food and Drug Administration granted an emergency authorization for the surgery through its single-patient investigational new drug compassionate use pathway. 

“My only real hope left is to go with the pig heart, the xenotransplant,” Mr. Faucette said in an interview from his hospital room a few days before his surgery. “At least now I have hope, and I have a chance.” He made “significant progress” in the month after the surgery, participating in physical therapy and spending time with family, according to the university. But in the days before his death, the heart showed signs of rejection.

“Mr. Faucette’s last wish was for us to make the most of what we have learned from our experience, so others may be guaranteed a chance for a new heart when a human organ is unavailable,” said Bartley P. Griffith, MD, who transplanted the pig heart into Mr. Faucette at UMMC. “He then told the team of doctors and nurses who gathered around him that he loved us. We will miss him tremendously.”

Muhammad M. Mohiuddin, MD, professor of surgery and scientific/program director of the Cardiac Xenotransplantation Program at the University of Maryland School of Medicine, said that “Mr. Faucette was a scientist who not only read and interpreted his own biopsies, but who understood the important contribution he was making in advancing the field.

“As with the first patient, David Bennett Sr., we intend to conduct an extensive analysis to identify factors that can be prevented in future transplants; this will allow us to continue to move forward and educate our colleagues in the field on our experience,” Dr. Mohiuddin added.

The researchers don’t plan to make further comments until their investigation is complete, a university spokesperson said in an interview.

UMMC performed the first transplant of a genetically modified pig heart in January 2022. Mr. Bennett, the recipient of that heart, survived for 60 days. The researchers published their initial findings in The New England Journal of Medicine, and then the results of their follow-up investigation in The Lancet.
 

A version of this article first appeared on Medscape.com.

Lawrence Faucette, the 58-year-old man with terminal heart disease who received the world’s second genetically modified pig heart transplant, died on Oct. 30, 2023, the University of Maryland Medical Center (UMMC), Baltimore, reported in a statement.

Mr. Faucette, a former lab tech who was turned down repeatedly for a standard allograft transplantation because of his various medical conditions, received the pig heart transplant on Sept. 20, 2023.

He first came to UMMC as a patient on Sept. 14. When he was admitted, he was in end-stage heart failure. Shortly before the surgery, his heart stopped, and he required resuscitation.

On Sept. 15, the Food and Drug Administration granted an emergency authorization for the surgery through its single-patient investigational new drug compassionate use pathway. 

“My only real hope left is to go with the pig heart, the xenotransplant,” Mr. Faucette said in an interview from his hospital room a few days before his surgery. “At least now I have hope, and I have a chance.” He made “significant progress” in the month after the surgery, participating in physical therapy and spending time with family, according to the university. But in the days before his death, the heart showed signs of rejection.

“Mr. Faucette’s last wish was for us to make the most of what we have learned from our experience, so others may be guaranteed a chance for a new heart when a human organ is unavailable,” said Bartley P. Griffith, MD, who transplanted the pig heart into Mr. Faucette at UMMC. “He then told the team of doctors and nurses who gathered around him that he loved us. We will miss him tremendously.”

Muhammad M. Mohiuddin, MD, professor of surgery and scientific/program director of the Cardiac Xenotransplantation Program at the University of Maryland School of Medicine, said that “Mr. Faucette was a scientist who not only read and interpreted his own biopsies, but who understood the important contribution he was making in advancing the field.

“As with the first patient, David Bennett Sr., we intend to conduct an extensive analysis to identify factors that can be prevented in future transplants; this will allow us to continue to move forward and educate our colleagues in the field on our experience,” Dr. Mohiuddin added.

The researchers don’t plan to make further comments until their investigation is complete, a university spokesperson said in an interview.

UMMC performed the first transplant of a genetically modified pig heart in January 2022. Mr. Bennett, the recipient of that heart, survived for 60 days. The researchers published their initial findings in The New England Journal of Medicine, and then the results of their follow-up investigation in The Lancet.
 

A version of this article first appeared on Medscape.com.

Lawrence Faucette, the 58-year-old man with terminal heart disease who received the world’s second genetically modified pig heart transplant, died on Oct. 30, 2023, the University of Maryland Medical Center (UMMC), Baltimore, reported in a statement.

Mr. Faucette, a former lab tech who was turned down repeatedly for a standard allograft transplantation because of his various medical conditions, received the pig heart transplant on Sept. 20, 2023.

He first came to UMMC as a patient on Sept. 14. When he was admitted, he was in end-stage heart failure. Shortly before the surgery, his heart stopped, and he required resuscitation.

On Sept. 15, the Food and Drug Administration granted an emergency authorization for the surgery through its single-patient investigational new drug compassionate use pathway. 

“My only real hope left is to go with the pig heart, the xenotransplant,” Mr. Faucette said in an interview from his hospital room a few days before his surgery. “At least now I have hope, and I have a chance.” He made “significant progress” in the month after the surgery, participating in physical therapy and spending time with family, according to the university. But in the days before his death, the heart showed signs of rejection.

“Mr. Faucette’s last wish was for us to make the most of what we have learned from our experience, so others may be guaranteed a chance for a new heart when a human organ is unavailable,” said Bartley P. Griffith, MD, who transplanted the pig heart into Mr. Faucette at UMMC. “He then told the team of doctors and nurses who gathered around him that he loved us. We will miss him tremendously.”

Muhammad M. Mohiuddin, MD, professor of surgery and scientific/program director of the Cardiac Xenotransplantation Program at the University of Maryland School of Medicine, said that “Mr. Faucette was a scientist who not only read and interpreted his own biopsies, but who understood the important contribution he was making in advancing the field.

“As with the first patient, David Bennett Sr., we intend to conduct an extensive analysis to identify factors that can be prevented in future transplants; this will allow us to continue to move forward and educate our colleagues in the field on our experience,” Dr. Mohiuddin added.

The researchers don’t plan to make further comments until their investigation is complete, a university spokesperson said in an interview.

UMMC performed the first transplant of a genetically modified pig heart in January 2022. Mr. Bennett, the recipient of that heart, survived for 60 days. The researchers published their initial findings in The New England Journal of Medicine, and then the results of their follow-up investigation in The Lancet.
 

A version of this article first appeared on Medscape.com.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved infliximab-dyyb (Zymfentra, Celltrion USA) for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD) after treatment with an intravenous infliximab product.

Infliximab-dyyb is a subcutaneous formulation of Celltrion’s infliximab. The FDA approval provides an alternative administration option for delivering the drug, which blocks the action of tumor necrosis factor alpha.

The new formulation was approved based on phase 3 pivotal trials that evaluated the safety and efficacy of infliximab-dyyb as maintenance therapy in patients with moderately to severely active UC (LIBERTY-UC) and CD (LIBERTY-CD).

In both 54-week trials, infliximab-dyyb demonstrated superiority to placebo in the primary endpoints of clinical remission (UC and CD) and endoscopic response (CD) when given as maintenance therapy after induction therapy with IV infliximab.

The overall safety profile of infliximab-dyyb was similar to that of the placebo during the maintenance period in both studies, with no new safety signals seen.

In the randomized, placebo-controlled, double-blind LIBERTY-UC study, 438 patients with moderately to severely active UC after induction therapy with IV infliximab were randomly assigned at week 10. The rate of clinical remission at week 54 was significantly greater with infliximab-dyyb (43.2%), compared with placebo (20.8%).

The most common adverse events were COVID-19, anemia, arthralgia, injection site reaction, increased alanine aminotransferase, and abdominal pain.

In the similarly designed LIBERTY-CD study, 343 patients with moderately to severely active CD after induction therapy were randomly assigned at week 10. At week 54, the clinical remission rate was greater with infliximab-dyyb (62.3%) than with placebo (32.1%).

In parallel, the endoscopic response rate at week 54 was also greater in the infliximab-dyyb arm than in the placebo arm (51.1% vs. 17.9%, respectively).

The safety profile during the maintenance phase was generally comparable between the two trial arms. The most common adverse events were COVID-19, upper respiratory tract infection, headache, injection site reaction, diarrhea, increased alanine aminotransferase, increased blood creatine phosphokinase, neutropenia, hypertension, urinary tract infection, dizziness, and leukopenia.

Full prescribing information is available online.

“As someone dedicated to improving the lives of patients with IBD, I am excited to see data supporting the efficacy and safety of a new formulation offering convenience and improved access to a well-known and proven drug,” Andres Yarur, MD, of Cedars-Sinai Medical Center, Los Angeles, said in a news release. 

The data “validate a convenient treatment option that could allow more patients in the United States to have greater control of their disease management,” added Jean-Frederic Colombel, MD, of Icahn School of Medicine at Mount Sinai, New York.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved infliximab-dyyb (Zymfentra, Celltrion USA) for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD) after treatment with an intravenous infliximab product.

Infliximab-dyyb is a subcutaneous formulation of Celltrion’s infliximab. The FDA approval provides an alternative administration option for delivering the drug, which blocks the action of tumor necrosis factor alpha.

The new formulation was approved based on phase 3 pivotal trials that evaluated the safety and efficacy of infliximab-dyyb as maintenance therapy in patients with moderately to severely active UC (LIBERTY-UC) and CD (LIBERTY-CD).

In both 54-week trials, infliximab-dyyb demonstrated superiority to placebo in the primary endpoints of clinical remission (UC and CD) and endoscopic response (CD) when given as maintenance therapy after induction therapy with IV infliximab.

The overall safety profile of infliximab-dyyb was similar to that of the placebo during the maintenance period in both studies, with no new safety signals seen.

In the randomized, placebo-controlled, double-blind LIBERTY-UC study, 438 patients with moderately to severely active UC after induction therapy with IV infliximab were randomly assigned at week 10. The rate of clinical remission at week 54 was significantly greater with infliximab-dyyb (43.2%), compared with placebo (20.8%).

The most common adverse events were COVID-19, anemia, arthralgia, injection site reaction, increased alanine aminotransferase, and abdominal pain.

In the similarly designed LIBERTY-CD study, 343 patients with moderately to severely active CD after induction therapy were randomly assigned at week 10. At week 54, the clinical remission rate was greater with infliximab-dyyb (62.3%) than with placebo (32.1%).

In parallel, the endoscopic response rate at week 54 was also greater in the infliximab-dyyb arm than in the placebo arm (51.1% vs. 17.9%, respectively).

The safety profile during the maintenance phase was generally comparable between the two trial arms. The most common adverse events were COVID-19, upper respiratory tract infection, headache, injection site reaction, diarrhea, increased alanine aminotransferase, increased blood creatine phosphokinase, neutropenia, hypertension, urinary tract infection, dizziness, and leukopenia.

Full prescribing information is available online.

“As someone dedicated to improving the lives of patients with IBD, I am excited to see data supporting the efficacy and safety of a new formulation offering convenience and improved access to a well-known and proven drug,” Andres Yarur, MD, of Cedars-Sinai Medical Center, Los Angeles, said in a news release. 

The data “validate a convenient treatment option that could allow more patients in the United States to have greater control of their disease management,” added Jean-Frederic Colombel, MD, of Icahn School of Medicine at Mount Sinai, New York.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved infliximab-dyyb (Zymfentra, Celltrion USA) for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD) after treatment with an intravenous infliximab product.

Infliximab-dyyb is a subcutaneous formulation of Celltrion’s infliximab. The FDA approval provides an alternative administration option for delivering the drug, which blocks the action of tumor necrosis factor alpha.

The new formulation was approved based on phase 3 pivotal trials that evaluated the safety and efficacy of infliximab-dyyb as maintenance therapy in patients with moderately to severely active UC (LIBERTY-UC) and CD (LIBERTY-CD).

In both 54-week trials, infliximab-dyyb demonstrated superiority to placebo in the primary endpoints of clinical remission (UC and CD) and endoscopic response (CD) when given as maintenance therapy after induction therapy with IV infliximab.

The overall safety profile of infliximab-dyyb was similar to that of the placebo during the maintenance period in both studies, with no new safety signals seen.

In the randomized, placebo-controlled, double-blind LIBERTY-UC study, 438 patients with moderately to severely active UC after induction therapy with IV infliximab were randomly assigned at week 10. The rate of clinical remission at week 54 was significantly greater with infliximab-dyyb (43.2%), compared with placebo (20.8%).

The most common adverse events were COVID-19, anemia, arthralgia, injection site reaction, increased alanine aminotransferase, and abdominal pain.

In the similarly designed LIBERTY-CD study, 343 patients with moderately to severely active CD after induction therapy were randomly assigned at week 10. At week 54, the clinical remission rate was greater with infliximab-dyyb (62.3%) than with placebo (32.1%).

In parallel, the endoscopic response rate at week 54 was also greater in the infliximab-dyyb arm than in the placebo arm (51.1% vs. 17.9%, respectively).

The safety profile during the maintenance phase was generally comparable between the two trial arms. The most common adverse events were COVID-19, upper respiratory tract infection, headache, injection site reaction, diarrhea, increased alanine aminotransferase, increased blood creatine phosphokinase, neutropenia, hypertension, urinary tract infection, dizziness, and leukopenia.

Full prescribing information is available online.

“As someone dedicated to improving the lives of patients with IBD, I am excited to see data supporting the efficacy and safety of a new formulation offering convenience and improved access to a well-known and proven drug,” Andres Yarur, MD, of Cedars-Sinai Medical Center, Los Angeles, said in a news release. 

The data “validate a convenient treatment option that could allow more patients in the United States to have greater control of their disease management,” added Jean-Frederic Colombel, MD, of Icahn School of Medicine at Mount Sinai, New York.

A version of this article first appeared on Medscape.com.