Clinician Reviews

More than 15 years in the making, the revised AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was released in 2022. A key driving force for this revision was the expanded evidence base regarding monitoring and treatment of newborns 35 or more weeks’ gestation to prevent bilirubin encephalopathy and kernicterus.

Here, we summarize the highlights of the new guidelines and point out practical ways to incorporate these guidelines into daily practice.
 

What has changed?

If you are familiar with the previous guidelines (2004 or the 2009 update) for the management of newborn jaundice, you’ll note that the treatment graphs for phototherapy and exchange transfusion have been updated with new, slightly higher thresholds.

Bilirubin thresholds for starting phototherapy are about 2 mg/dL higher overall than indicated in previous iterations of the guidelines.

This change reflects new evidence that infants don’t typically develop bilirubin neurotoxicity until the total serum bilirubin (TSB) reaches levels well above the previous exchange transfusion threshold, justifying a narrow increase in the bilirubin level for starting phototherapy. Also, phototherapy treatment thresholds are now risk-adjusted, with separate curves for each gestational age from 35 weeks to > 38 weeks.

To find the applicable phototherapy threshold, use the infant’s gestational age (rounding down) and determine whether the infant has even a single neurotoxicity risk factor other than prematurity. Neurotoxicity risk factors include a low albumin level, isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.

For example, a 38^4/7 weeks’ gestation newborn has a TSB of 12 mg/dL at 48 hours of age but no neurotoxicity risk factors. Using the graph Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors, should the infant be placed under phototherapy at this time? (Answer: No. The threshold for starting phototherapy on this infant is approximately 16 mg/dL.)

When hyperbilirubinemia becomes a medical emergency

A new term, “escalation of care,” has been adopted to describe actions to take when the newborn’s TSB climbs to within 2 mg/dL of the exchange transfusion threshold – a medical emergency. Instructions on how to ensure intensive phototherapy, and when to initiate an urgent exchange transfusion, are given, including the critical need to maintain intensive phototherapy continuously during infant transport and admission to another facility.

Transcutaneous vs. serum bilirubin

Either a serum TSB or a transcutaneous bilirubin (TcB) should be measured in all infants between 24 and 48 hours after birth or before discharge if that occurs earlier. TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement. Although the two tests are generally correlated, they are not identical, and treatment decisions should be based on TSB levels. A TSB should be obtained if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold, or if the TcB is ≥ 15 mg/dL.

Following up: When to check another bilirubin level

Prior to these new guidelines, the question of when to get the next bilirubin level was based on Vinod Bhutani, MD’s risk nomogram, which classified newborn bilirubin levels within high-, intermediate-, or low-risk zones for needing phototherapy. A bilirubin level in the high-risk zone indicated the need for earlier follow-up. These risk zones have been replaced with a more specific table that provides recommended postdischarge follow-up based on how close the newborn’s bilirubin level is to the hour-specific threshold for treatment. The closer the latest TSB or TcB level is to the newborn’s risk-based phototherapy threshold, the sooner the follow-up to check another bilirubin level will need to be.

Most infants discharged before 72 hours of age will need follow-up within 2 days. Newborns with TSB levels nearing the level for phototherapy (within 2 mg/dL or less) should remain in the hospital.
 

Five tips for using the new guidelines

Bilitool.org, a popular and useful app, has already been updated to reflect the changes in the new guidelines, making it easy to apply the new thresholds and create a follow-up plan for each patient.

The guidelines provide recommendations for when to check rebound bilirubin levels after stopping phototherapy (hint: babies with neurotoxic risk factors). A TcB device should not be used while the infant is being treated with phototherapy. However, a TcB can be measured once the baby has been off phototherapy for at least 24 hours.

If you have at least two bilirubin measurements, you can calculate the “rate of rise” in bilirubin level. A rapid rate of rise, which serves as a clinical indicator of hemolysis, is defined as ≥ 0.3 mg/dL per hour in the first 24 hours or ≥ 0.2 mg/dL per hour after the first 24 hours of life. This is especially helpful when hemolysis is suspected even if the newborn’s direct antibody test (DAT) is negative. In this scenario, the infant is considered to have a neurotoxic risk factor.

When you initiate phototherapy, be aware of the infant’s bilirubin level threshold for stopping phototherapy (2 mg/dL below the starting phototherapy threshold), as well as the threshold for escalation of care (2 mg/dL below the exchange transfusion threshold).

Because the thresholds for starting phototherapy and initiating exchange transfusion are slightly higher and specific to gestational age, clinicians can more confidently use less phototherapy.
 

Other guideline highlights

The neurotoxic risk factors and corresponding thresholds are important. If the newborn has one or more neurotoxic risk factors other than prematurity, the neurotoxic risk threshold graph should be used when assessing the need for treatment. Neurotoxic risk thresholds should also be used for newborns whose bilirubin levels continue rising on phototherapy.

The guidelines emphasize that G6PD is one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and worldwide. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.

Finally, the guidelines remind clinicians that an important way to reduce the chances that phototherapy will be needed is to encourage early and frequent feeding (8-12 times in 24 hours).

The AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation contains a great deal more information, but these basic principles should allow practitioners to begin to incorporate these guidelines into daily practice.

Dr. Amaya is associate professor, department of pediatrics, Medical University of South Carolina, Charleston, and medical director, level 1 nursery, department of pediatrics, MUSC general academic pediatrics. She disclosed ties with Medical University of South Carolina. Dr. Balog is clinical associate professor of pediatrics, Medical University of South Carolina, Charleston. She has no relevant financial relationships. Dr. Basco is professor, department of pediatrics, Medical University of South Carolina, Charleston; director, division of general pediatrics, department of pediatrics, MUSC Children’s Hospital. He has disclosed no relevant financial relationships.

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

More than 15 years in the making, the revised AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was released in 2022. A key driving force for this revision was the expanded evidence base regarding monitoring and treatment of newborns 35 or more weeks’ gestation to prevent bilirubin encephalopathy and kernicterus.

Here, we summarize the highlights of the new guidelines and point out practical ways to incorporate these guidelines into daily practice.
 

What has changed?

If you are familiar with the previous guidelines (2004 or the 2009 update) for the management of newborn jaundice, you’ll note that the treatment graphs for phototherapy and exchange transfusion have been updated with new, slightly higher thresholds.

Bilirubin thresholds for starting phototherapy are about 2 mg/dL higher overall than indicated in previous iterations of the guidelines.

This change reflects new evidence that infants don’t typically develop bilirubin neurotoxicity until the total serum bilirubin (TSB) reaches levels well above the previous exchange transfusion threshold, justifying a narrow increase in the bilirubin level for starting phototherapy. Also, phototherapy treatment thresholds are now risk-adjusted, with separate curves for each gestational age from 35 weeks to > 38 weeks.

To find the applicable phototherapy threshold, use the infant’s gestational age (rounding down) and determine whether the infant has even a single neurotoxicity risk factor other than prematurity. Neurotoxicity risk factors include a low albumin level, isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.

For example, a 38^4/7 weeks’ gestation newborn has a TSB of 12 mg/dL at 48 hours of age but no neurotoxicity risk factors. Using the graph Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors, should the infant be placed under phototherapy at this time? (Answer: No. The threshold for starting phototherapy on this infant is approximately 16 mg/dL.)

When hyperbilirubinemia becomes a medical emergency

A new term, “escalation of care,” has been adopted to describe actions to take when the newborn’s TSB climbs to within 2 mg/dL of the exchange transfusion threshold – a medical emergency. Instructions on how to ensure intensive phototherapy, and when to initiate an urgent exchange transfusion, are given, including the critical need to maintain intensive phototherapy continuously during infant transport and admission to another facility.

Transcutaneous vs. serum bilirubin

Either a serum TSB or a transcutaneous bilirubin (TcB) should be measured in all infants between 24 and 48 hours after birth or before discharge if that occurs earlier. TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement. Although the two tests are generally correlated, they are not identical, and treatment decisions should be based on TSB levels. A TSB should be obtained if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold, or if the TcB is ≥ 15 mg/dL.

Following up: When to check another bilirubin level

Prior to these new guidelines, the question of when to get the next bilirubin level was based on Vinod Bhutani, MD’s risk nomogram, which classified newborn bilirubin levels within high-, intermediate-, or low-risk zones for needing phototherapy. A bilirubin level in the high-risk zone indicated the need for earlier follow-up. These risk zones have been replaced with a more specific table that provides recommended postdischarge follow-up based on how close the newborn’s bilirubin level is to the hour-specific threshold for treatment. The closer the latest TSB or TcB level is to the newborn’s risk-based phototherapy threshold, the sooner the follow-up to check another bilirubin level will need to be.

Most infants discharged before 72 hours of age will need follow-up within 2 days. Newborns with TSB levels nearing the level for phototherapy (within 2 mg/dL or less) should remain in the hospital.
 

Five tips for using the new guidelines

Bilitool.org, a popular and useful app, has already been updated to reflect the changes in the new guidelines, making it easy to apply the new thresholds and create a follow-up plan for each patient.

The guidelines provide recommendations for when to check rebound bilirubin levels after stopping phototherapy (hint: babies with neurotoxic risk factors). A TcB device should not be used while the infant is being treated with phototherapy. However, a TcB can be measured once the baby has been off phototherapy for at least 24 hours.

If you have at least two bilirubin measurements, you can calculate the “rate of rise” in bilirubin level. A rapid rate of rise, which serves as a clinical indicator of hemolysis, is defined as ≥ 0.3 mg/dL per hour in the first 24 hours or ≥ 0.2 mg/dL per hour after the first 24 hours of life. This is especially helpful when hemolysis is suspected even if the newborn’s direct antibody test (DAT) is negative. In this scenario, the infant is considered to have a neurotoxic risk factor.

When you initiate phototherapy, be aware of the infant’s bilirubin level threshold for stopping phototherapy (2 mg/dL below the starting phototherapy threshold), as well as the threshold for escalation of care (2 mg/dL below the exchange transfusion threshold).

Because the thresholds for starting phototherapy and initiating exchange transfusion are slightly higher and specific to gestational age, clinicians can more confidently use less phototherapy.
 

Other guideline highlights

The neurotoxic risk factors and corresponding thresholds are important. If the newborn has one or more neurotoxic risk factors other than prematurity, the neurotoxic risk threshold graph should be used when assessing the need for treatment. Neurotoxic risk thresholds should also be used for newborns whose bilirubin levels continue rising on phototherapy.

The guidelines emphasize that G6PD is one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and worldwide. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.

Finally, the guidelines remind clinicians that an important way to reduce the chances that phototherapy will be needed is to encourage early and frequent feeding (8-12 times in 24 hours).

The AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation contains a great deal more information, but these basic principles should allow practitioners to begin to incorporate these guidelines into daily practice.

Dr. Amaya is associate professor, department of pediatrics, Medical University of South Carolina, Charleston, and medical director, level 1 nursery, department of pediatrics, MUSC general academic pediatrics. She disclosed ties with Medical University of South Carolina. Dr. Balog is clinical associate professor of pediatrics, Medical University of South Carolina, Charleston. She has no relevant financial relationships. Dr. Basco is professor, department of pediatrics, Medical University of South Carolina, Charleston; director, division of general pediatrics, department of pediatrics, MUSC Children’s Hospital. He has disclosed no relevant financial relationships.

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

More than 15 years in the making, the revised AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation was released in 2022. A key driving force for this revision was the expanded evidence base regarding monitoring and treatment of newborns 35 or more weeks’ gestation to prevent bilirubin encephalopathy and kernicterus.

Here, we summarize the highlights of the new guidelines and point out practical ways to incorporate these guidelines into daily practice.
 

What has changed?

If you are familiar with the previous guidelines (2004 or the 2009 update) for the management of newborn jaundice, you’ll note that the treatment graphs for phototherapy and exchange transfusion have been updated with new, slightly higher thresholds.

Bilirubin thresholds for starting phototherapy are about 2 mg/dL higher overall than indicated in previous iterations of the guidelines.

This change reflects new evidence that infants don’t typically develop bilirubin neurotoxicity until the total serum bilirubin (TSB) reaches levels well above the previous exchange transfusion threshold, justifying a narrow increase in the bilirubin level for starting phototherapy. Also, phototherapy treatment thresholds are now risk-adjusted, with separate curves for each gestational age from 35 weeks to > 38 weeks.

To find the applicable phototherapy threshold, use the infant’s gestational age (rounding down) and determine whether the infant has even a single neurotoxicity risk factor other than prematurity. Neurotoxicity risk factors include a low albumin level, isoimmune hemolytic disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency, or other hemolytic conditions; sepsis; or any significant clinical instability in the previous 24 hours.

For example, a 38^4/7 weeks’ gestation newborn has a TSB of 12 mg/dL at 48 hours of age but no neurotoxicity risk factors. Using the graph Phototherapy Thresholds: No Hyperbilirubinemia Neurotoxicity Risk Factors, should the infant be placed under phototherapy at this time? (Answer: No. The threshold for starting phototherapy on this infant is approximately 16 mg/dL.)

When hyperbilirubinemia becomes a medical emergency

A new term, “escalation of care,” has been adopted to describe actions to take when the newborn’s TSB climbs to within 2 mg/dL of the exchange transfusion threshold – a medical emergency. Instructions on how to ensure intensive phototherapy, and when to initiate an urgent exchange transfusion, are given, including the critical need to maintain intensive phototherapy continuously during infant transport and admission to another facility.

Transcutaneous vs. serum bilirubin

Either a serum TSB or a transcutaneous bilirubin (TcB) should be measured in all infants between 24 and 48 hours after birth or before discharge if that occurs earlier. TcB measurements are valid and reliable when used as a screening test to identify infants who require a TSB measurement. Although the two tests are generally correlated, they are not identical, and treatment decisions should be based on TSB levels. A TSB should be obtained if the TcB exceeds or is within 3 mg/dL of the phototherapy treatment threshold, or if the TcB is ≥ 15 mg/dL.

Following up: When to check another bilirubin level

Prior to these new guidelines, the question of when to get the next bilirubin level was based on Vinod Bhutani, MD’s risk nomogram, which classified newborn bilirubin levels within high-, intermediate-, or low-risk zones for needing phototherapy. A bilirubin level in the high-risk zone indicated the need for earlier follow-up. These risk zones have been replaced with a more specific table that provides recommended postdischarge follow-up based on how close the newborn’s bilirubin level is to the hour-specific threshold for treatment. The closer the latest TSB or TcB level is to the newborn’s risk-based phototherapy threshold, the sooner the follow-up to check another bilirubin level will need to be.

Most infants discharged before 72 hours of age will need follow-up within 2 days. Newborns with TSB levels nearing the level for phototherapy (within 2 mg/dL or less) should remain in the hospital.
 

Five tips for using the new guidelines

Bilitool.org, a popular and useful app, has already been updated to reflect the changes in the new guidelines, making it easy to apply the new thresholds and create a follow-up plan for each patient.

The guidelines provide recommendations for when to check rebound bilirubin levels after stopping phototherapy (hint: babies with neurotoxic risk factors). A TcB device should not be used while the infant is being treated with phototherapy. However, a TcB can be measured once the baby has been off phototherapy for at least 24 hours.

If you have at least two bilirubin measurements, you can calculate the “rate of rise” in bilirubin level. A rapid rate of rise, which serves as a clinical indicator of hemolysis, is defined as ≥ 0.3 mg/dL per hour in the first 24 hours or ≥ 0.2 mg/dL per hour after the first 24 hours of life. This is especially helpful when hemolysis is suspected even if the newborn’s direct antibody test (DAT) is negative. In this scenario, the infant is considered to have a neurotoxic risk factor.

When you initiate phototherapy, be aware of the infant’s bilirubin level threshold for stopping phototherapy (2 mg/dL below the starting phototherapy threshold), as well as the threshold for escalation of care (2 mg/dL below the exchange transfusion threshold).

Because the thresholds for starting phototherapy and initiating exchange transfusion are slightly higher and specific to gestational age, clinicians can more confidently use less phototherapy.
 

Other guideline highlights

The neurotoxic risk factors and corresponding thresholds are important. If the newborn has one or more neurotoxic risk factors other than prematurity, the neurotoxic risk threshold graph should be used when assessing the need for treatment. Neurotoxic risk thresholds should also be used for newborns whose bilirubin levels continue rising on phototherapy.

The guidelines emphasize that G6PD is one of the most important causes of hazardous hyperbilirubinemia leading to kernicterus in the United States and worldwide. Overall, 13% of African American males and about 4% of African American females have G6PD deficiency.

Finally, the guidelines remind clinicians that an important way to reduce the chances that phototherapy will be needed is to encourage early and frequent feeding (8-12 times in 24 hours).

The AAP Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation contains a great deal more information, but these basic principles should allow practitioners to begin to incorporate these guidelines into daily practice.

Dr. Amaya is associate professor, department of pediatrics, Medical University of South Carolina, Charleston, and medical director, level 1 nursery, department of pediatrics, MUSC general academic pediatrics. She disclosed ties with Medical University of South Carolina. Dr. Balog is clinical associate professor of pediatrics, Medical University of South Carolina, Charleston. She has no relevant financial relationships. Dr. Basco is professor, department of pediatrics, Medical University of South Carolina, Charleston; director, division of general pediatrics, department of pediatrics, MUSC Children’s Hospital. He has disclosed no relevant financial relationships.

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

As a general practitioner with a specialist interest in diabetes, I am increasingly diagnosing younger people living with type 2 diabetes and obesity. Sadly, my youngest patient living with type 2 diabetes and obesity is only in her early 20s.
 

In fact, in England, there are now more people under the age of 40 years living with type 2 diabetes than type 1 diabetes. These younger individuals tend to present with very high hemoglobin A1c levels; I am routinely seeing double-digit A1c percentage levels in my practice. Indeed, the patient mentioned above presented with an A1c of more than 13%.

The lifetime cardiometabolic risk of individuals like her is considerable and very worrying: Younger adults with type 2 diabetes often have adverse cardiometabolic risk profiles at diagnosis, with higher body mass indices, marked dyslipidemia, hypertension, and abnormal liver profiles suggesting nonalcoholic fatty liver disease. The cumulative impact of this risk profile is a significant impact on quality and quantity of life. Evidence tells us that a younger age of diagnosis with type 2 diabetes is associated with an increased risk for premature death, especially from cardiovascular disease.

Early treatment intensification is warranted in younger individuals living with type 2 diabetes and obesity. My patient above is now on triple therapy with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a glucagonlike peptide–1 (GLP-1) receptor agonist. I gave her an urgent referral to my local weight management service for weight, nutritional, and psychological support. I have also issued her a real-time continuous glucose monitoring (rt-CGM) device: Whilst she does not meet any current U.K. criteria for using rt-CGM, I feel that the role of CGM as an educational tool for her is invaluable and equally important to her pharmacologic therapies. We are in desperate need of effective pharmacologic and lifestyle interventions to tackle this epidemic of cardiometabolic disease in the young.

I attended the recent ADA 2023 congress in San Diego, including the presentation of the SURMOUNT-2 trial data. SURMOUNT-2 explored the efficacy and safety of the dual GLP-GIP agonist tirzepatide for weight management in patients with obesity and type 2 diabetes. Tirzepatide was associated with significant reductions in weight (average weight loss, 14-16 kg after 72 weeks) and glycemia (2.1% reduction in A1c after 72 weeks), as well as reductions in clinically meaningful cardiometabolic risk factors, including systolic blood pressure, liver enzymes, and fasting non–HDL cholesterol levels. The overall safety profile of tirzepatide was also reassuring and consistent with the GLP-1 class. Most adverse effects were gastrointestinal and of mild to moderate severity. These adverse effects decreased over time.

These results perfectly position tirzepatide for my younger patients like the young woman mentioned above. The significant improvements in weight, glycemia, and cardiometabolic risk factors will not only help mitigate her future cardiometabolic risk but also help the sustainability of the U.K.’s National Health System. The cost of diabetes to the NHS in the United Kingdom is more than 10% of the entire NHS budget for England and Wales. More than 80% of this cost, however, is related not to the medications and devices we prescribe for diabetes but to the downstream complications of diabetes, such as hospital admissions for cardiovascular events and amputations, as well as regular hospital attendance for dialysis for end-stage kidney disease.

There is no doubt, however, that modern obesity medications such as semaglutide and tirzepatide are expensive, and demand has been astronomical. This demand has been driven by private weight-management services and celebrity influencers, and has resulted in major U.K.-wide GLP-1 shortages.

This situation is tragically widening health inequalities, as many of my patients who have been on GLP-1 receptor agonists for many years are unable to obtain them. I am having to consider switching therapies, often to less efficacious options without the compelling cardiorenal benefits. Furthermore, the GLP-1 shortages have prevented GLP-1 initiation for my other high-risk younger patients, potentially increasing future cardiometabolic risk.

There remain unanswered questions for tirzepatide: What is the durability of effect of tirzepatide after 72 weeks (that is, the trial duration of SURMOUNT-2)? Crucially, what is the effect of withdrawal of tirzepatide on weight loss maintenance? Previous evidence has suggested weight regain after discontinuation of a GLP-1 receptor agonist for obesity. This, of course, has further financial and sustainability implications for health care systems such as the NHS.

Finally, we are increasingly seeing younger women of childbearing age with or at risk for cardiometabolic disease. Again, my patient above is one example. Many of the therapies we use for cardiometabolic disease management, including GLP-1 receptor agonists and tirzepatide, have not been studied, and hence have not been licensed in pregnant women. Therefore, frank discussions are required with patients about future family plans and the importance of contraception. Often, the significant weight loss seen with GLP-1 receptor agonists can improve hormonal profiles and fertility in women and result in unexpected pregnancies if robust contraception is not in place.

Tirzepatide has yet to be made commercially available in the United Kingdom, and its price has also yet to be set. But I already envision a clear role for tirzepatide in my treatment armamentarium. I will be positioning tirzepatide as my first injectable of choice after oral treatment escalation with metformin and an SGLT2 inhibitor in all my patients who require treatment intensification – not just my younger, higher-risk individuals. This may remain an aspirational goal until supply chains and cost are defined. There is no doubt, however, that the compelling weight and glycemic benefits of tirzepatide alongside individualized lifestyle interventions can help improve the quality and quantity of life of my patients living with type 2 diabetes and obesity.

Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk..

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

As a general practitioner with a specialist interest in diabetes, I am increasingly diagnosing younger people living with type 2 diabetes and obesity. Sadly, my youngest patient living with type 2 diabetes and obesity is only in her early 20s.
 

In fact, in England, there are now more people under the age of 40 years living with type 2 diabetes than type 1 diabetes. These younger individuals tend to present with very high hemoglobin A1c levels; I am routinely seeing double-digit A1c percentage levels in my practice. Indeed, the patient mentioned above presented with an A1c of more than 13%.

The lifetime cardiometabolic risk of individuals like her is considerable and very worrying: Younger adults with type 2 diabetes often have adverse cardiometabolic risk profiles at diagnosis, with higher body mass indices, marked dyslipidemia, hypertension, and abnormal liver profiles suggesting nonalcoholic fatty liver disease. The cumulative impact of this risk profile is a significant impact on quality and quantity of life. Evidence tells us that a younger age of diagnosis with type 2 diabetes is associated with an increased risk for premature death, especially from cardiovascular disease.

Early treatment intensification is warranted in younger individuals living with type 2 diabetes and obesity. My patient above is now on triple therapy with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a glucagonlike peptide–1 (GLP-1) receptor agonist. I gave her an urgent referral to my local weight management service for weight, nutritional, and psychological support. I have also issued her a real-time continuous glucose monitoring (rt-CGM) device: Whilst she does not meet any current U.K. criteria for using rt-CGM, I feel that the role of CGM as an educational tool for her is invaluable and equally important to her pharmacologic therapies. We are in desperate need of effective pharmacologic and lifestyle interventions to tackle this epidemic of cardiometabolic disease in the young.

I attended the recent ADA 2023 congress in San Diego, including the presentation of the SURMOUNT-2 trial data. SURMOUNT-2 explored the efficacy and safety of the dual GLP-GIP agonist tirzepatide for weight management in patients with obesity and type 2 diabetes. Tirzepatide was associated with significant reductions in weight (average weight loss, 14-16 kg after 72 weeks) and glycemia (2.1% reduction in A1c after 72 weeks), as well as reductions in clinically meaningful cardiometabolic risk factors, including systolic blood pressure, liver enzymes, and fasting non–HDL cholesterol levels. The overall safety profile of tirzepatide was also reassuring and consistent with the GLP-1 class. Most adverse effects were gastrointestinal and of mild to moderate severity. These adverse effects decreased over time.

These results perfectly position tirzepatide for my younger patients like the young woman mentioned above. The significant improvements in weight, glycemia, and cardiometabolic risk factors will not only help mitigate her future cardiometabolic risk but also help the sustainability of the U.K.’s National Health System. The cost of diabetes to the NHS in the United Kingdom is more than 10% of the entire NHS budget for England and Wales. More than 80% of this cost, however, is related not to the medications and devices we prescribe for diabetes but to the downstream complications of diabetes, such as hospital admissions for cardiovascular events and amputations, as well as regular hospital attendance for dialysis for end-stage kidney disease.

There is no doubt, however, that modern obesity medications such as semaglutide and tirzepatide are expensive, and demand has been astronomical. This demand has been driven by private weight-management services and celebrity influencers, and has resulted in major U.K.-wide GLP-1 shortages.

This situation is tragically widening health inequalities, as many of my patients who have been on GLP-1 receptor agonists for many years are unable to obtain them. I am having to consider switching therapies, often to less efficacious options without the compelling cardiorenal benefits. Furthermore, the GLP-1 shortages have prevented GLP-1 initiation for my other high-risk younger patients, potentially increasing future cardiometabolic risk.

There remain unanswered questions for tirzepatide: What is the durability of effect of tirzepatide after 72 weeks (that is, the trial duration of SURMOUNT-2)? Crucially, what is the effect of withdrawal of tirzepatide on weight loss maintenance? Previous evidence has suggested weight regain after discontinuation of a GLP-1 receptor agonist for obesity. This, of course, has further financial and sustainability implications for health care systems such as the NHS.

Finally, we are increasingly seeing younger women of childbearing age with or at risk for cardiometabolic disease. Again, my patient above is one example. Many of the therapies we use for cardiometabolic disease management, including GLP-1 receptor agonists and tirzepatide, have not been studied, and hence have not been licensed in pregnant women. Therefore, frank discussions are required with patients about future family plans and the importance of contraception. Often, the significant weight loss seen with GLP-1 receptor agonists can improve hormonal profiles and fertility in women and result in unexpected pregnancies if robust contraception is not in place.

Tirzepatide has yet to be made commercially available in the United Kingdom, and its price has also yet to be set. But I already envision a clear role for tirzepatide in my treatment armamentarium. I will be positioning tirzepatide as my first injectable of choice after oral treatment escalation with metformin and an SGLT2 inhibitor in all my patients who require treatment intensification – not just my younger, higher-risk individuals. This may remain an aspirational goal until supply chains and cost are defined. There is no doubt, however, that the compelling weight and glycemic benefits of tirzepatide alongside individualized lifestyle interventions can help improve the quality and quantity of life of my patients living with type 2 diabetes and obesity.

Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk..

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

As a general practitioner with a specialist interest in diabetes, I am increasingly diagnosing younger people living with type 2 diabetes and obesity. Sadly, my youngest patient living with type 2 diabetes and obesity is only in her early 20s.
 

In fact, in England, there are now more people under the age of 40 years living with type 2 diabetes than type 1 diabetes. These younger individuals tend to present with very high hemoglobin A1c levels; I am routinely seeing double-digit A1c percentage levels in my practice. Indeed, the patient mentioned above presented with an A1c of more than 13%.

The lifetime cardiometabolic risk of individuals like her is considerable and very worrying: Younger adults with type 2 diabetes often have adverse cardiometabolic risk profiles at diagnosis, with higher body mass indices, marked dyslipidemia, hypertension, and abnormal liver profiles suggesting nonalcoholic fatty liver disease. The cumulative impact of this risk profile is a significant impact on quality and quantity of life. Evidence tells us that a younger age of diagnosis with type 2 diabetes is associated with an increased risk for premature death, especially from cardiovascular disease.

Early treatment intensification is warranted in younger individuals living with type 2 diabetes and obesity. My patient above is now on triple therapy with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and a glucagonlike peptide–1 (GLP-1) receptor agonist. I gave her an urgent referral to my local weight management service for weight, nutritional, and psychological support. I have also issued her a real-time continuous glucose monitoring (rt-CGM) device: Whilst she does not meet any current U.K. criteria for using rt-CGM, I feel that the role of CGM as an educational tool for her is invaluable and equally important to her pharmacologic therapies. We are in desperate need of effective pharmacologic and lifestyle interventions to tackle this epidemic of cardiometabolic disease in the young.

I attended the recent ADA 2023 congress in San Diego, including the presentation of the SURMOUNT-2 trial data. SURMOUNT-2 explored the efficacy and safety of the dual GLP-GIP agonist tirzepatide for weight management in patients with obesity and type 2 diabetes. Tirzepatide was associated with significant reductions in weight (average weight loss, 14-16 kg after 72 weeks) and glycemia (2.1% reduction in A1c after 72 weeks), as well as reductions in clinically meaningful cardiometabolic risk factors, including systolic blood pressure, liver enzymes, and fasting non–HDL cholesterol levels. The overall safety profile of tirzepatide was also reassuring and consistent with the GLP-1 class. Most adverse effects were gastrointestinal and of mild to moderate severity. These adverse effects decreased over time.

These results perfectly position tirzepatide for my younger patients like the young woman mentioned above. The significant improvements in weight, glycemia, and cardiometabolic risk factors will not only help mitigate her future cardiometabolic risk but also help the sustainability of the U.K.’s National Health System. The cost of diabetes to the NHS in the United Kingdom is more than 10% of the entire NHS budget for England and Wales. More than 80% of this cost, however, is related not to the medications and devices we prescribe for diabetes but to the downstream complications of diabetes, such as hospital admissions for cardiovascular events and amputations, as well as regular hospital attendance for dialysis for end-stage kidney disease.

There is no doubt, however, that modern obesity medications such as semaglutide and tirzepatide are expensive, and demand has been astronomical. This demand has been driven by private weight-management services and celebrity influencers, and has resulted in major U.K.-wide GLP-1 shortages.

This situation is tragically widening health inequalities, as many of my patients who have been on GLP-1 receptor agonists for many years are unable to obtain them. I am having to consider switching therapies, often to less efficacious options without the compelling cardiorenal benefits. Furthermore, the GLP-1 shortages have prevented GLP-1 initiation for my other high-risk younger patients, potentially increasing future cardiometabolic risk.

There remain unanswered questions for tirzepatide: What is the durability of effect of tirzepatide after 72 weeks (that is, the trial duration of SURMOUNT-2)? Crucially, what is the effect of withdrawal of tirzepatide on weight loss maintenance? Previous evidence has suggested weight regain after discontinuation of a GLP-1 receptor agonist for obesity. This, of course, has further financial and sustainability implications for health care systems such as the NHS.

Finally, we are increasingly seeing younger women of childbearing age with or at risk for cardiometabolic disease. Again, my patient above is one example. Many of the therapies we use for cardiometabolic disease management, including GLP-1 receptor agonists and tirzepatide, have not been studied, and hence have not been licensed in pregnant women. Therefore, frank discussions are required with patients about future family plans and the importance of contraception. Often, the significant weight loss seen with GLP-1 receptor agonists can improve hormonal profiles and fertility in women and result in unexpected pregnancies if robust contraception is not in place.

Tirzepatide has yet to be made commercially available in the United Kingdom, and its price has also yet to be set. But I already envision a clear role for tirzepatide in my treatment armamentarium. I will be positioning tirzepatide as my first injectable of choice after oral treatment escalation with metformin and an SGLT2 inhibitor in all my patients who require treatment intensification – not just my younger, higher-risk individuals. This may remain an aspirational goal until supply chains and cost are defined. There is no doubt, however, that the compelling weight and glycemic benefits of tirzepatide alongside individualized lifestyle interventions can help improve the quality and quantity of life of my patients living with type 2 diabetes and obesity.

Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk..

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

A new scientific statement from the American Heart Association focuses on equity in cardio-oncology care and research.

A “growing body of evidence” suggests that women and people from underrepresented patient groups experience disproportionately higher cardiovascular effects from new and emerging anticancer therapies, the writing group, led by Daniel Addison, MD, with the Ohio State University, Columbus, pointed out.

For example, women appear to be at higher risk of immune checkpoint inhibitor–related toxicities, whereas Black patients with cancer face up to a threefold higher risk of cardiotoxicity with anticancer therapies.

With reduced screening and delayed preventive measures, Hispanic patients have more complex heart disease, cancer is diagnosed at later stages, and they receive more cardiotoxic regimens because of a lack of eligibility for novel treatments. Ultimately, this contributes to a higher incidence of treatment complications, cardiac dysfunction, and adverse patient outcomes for this patient group, they write.

Although no studies have specifically addressed cardio-oncology disparities in the LGBTQIA+ population, such disparities can be inferred from known cardiovascular disease and oncology disparities, the writing group noted.

These disparities are supported by “disparately high” risk of death after a cancer diagnosis among women and individuals from underrepresented groups, even after accounting for socioeconomic and behavioral patterns, they pointed out.

The scientific statement was published online in Circulation.
 

Evidence gaps and the path forward

“Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations,” the writing group said.

Decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigations, and potential optimal strategies to address disparate cardiotoxicity with contemporary cancer immunotherapy, as well as biologic and cytotoxic therapies, they noted.

They said caution is needed when interpreting clinical trial data about cardiotoxicity and in generalizing the results because people from diverse racial and ethnic groups have not been well represented in many trials.

The writing group outlined key evidence gaps and future research directions for addressing cardio-oncology disparities, as well as strategies to improve equity in cardio-oncology care and research.

These include the following:

• Identifying specific predictive factors of long-term cardiotoxic risk with targeted and immune-based cancer therapies in women and underrepresented populations.
• Investigating biological mechanisms that may underlie differences in cardiotoxicities between different patient groups.
• Developing personalized cardioprotection strategies that integrate biological, genetic, and social determinant markers.
• Intentionally diversifying clinical trials and identifying optimal strategies to improve representation in cancer clinical trials.
• Determining the role of technology, such as artificial intelligence, in improving cardiotoxicity disparities.

“Conscientiously leveraging technology and designing trials with outcomes related to these issues in practice (considering feasibility and cost) will critically accelerate the field of cardio-oncology in the 21st century. With tangible goals, we can improve health inequities in cardio-oncology,” the writing group said.

The research had no commercial funding. No conflicts of interest were reported.

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

A new scientific statement from the American Heart Association focuses on equity in cardio-oncology care and research.

A “growing body of evidence” suggests that women and people from underrepresented patient groups experience disproportionately higher cardiovascular effects from new and emerging anticancer therapies, the writing group, led by Daniel Addison, MD, with the Ohio State University, Columbus, pointed out.

For example, women appear to be at higher risk of immune checkpoint inhibitor–related toxicities, whereas Black patients with cancer face up to a threefold higher risk of cardiotoxicity with anticancer therapies.

With reduced screening and delayed preventive measures, Hispanic patients have more complex heart disease, cancer is diagnosed at later stages, and they receive more cardiotoxic regimens because of a lack of eligibility for novel treatments. Ultimately, this contributes to a higher incidence of treatment complications, cardiac dysfunction, and adverse patient outcomes for this patient group, they write.

Although no studies have specifically addressed cardio-oncology disparities in the LGBTQIA+ population, such disparities can be inferred from known cardiovascular disease and oncology disparities, the writing group noted.

These disparities are supported by “disparately high” risk of death after a cancer diagnosis among women and individuals from underrepresented groups, even after accounting for socioeconomic and behavioral patterns, they pointed out.

The scientific statement was published online in Circulation.
 

Evidence gaps and the path forward

“Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations,” the writing group said.

Decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigations, and potential optimal strategies to address disparate cardiotoxicity with contemporary cancer immunotherapy, as well as biologic and cytotoxic therapies, they noted.

They said caution is needed when interpreting clinical trial data about cardiotoxicity and in generalizing the results because people from diverse racial and ethnic groups have not been well represented in many trials.

The writing group outlined key evidence gaps and future research directions for addressing cardio-oncology disparities, as well as strategies to improve equity in cardio-oncology care and research.

These include the following:

• Identifying specific predictive factors of long-term cardiotoxic risk with targeted and immune-based cancer therapies in women and underrepresented populations.
• Investigating biological mechanisms that may underlie differences in cardiotoxicities between different patient groups.
• Developing personalized cardioprotection strategies that integrate biological, genetic, and social determinant markers.
• Intentionally diversifying clinical trials and identifying optimal strategies to improve representation in cancer clinical trials.
• Determining the role of technology, such as artificial intelligence, in improving cardiotoxicity disparities.

“Conscientiously leveraging technology and designing trials with outcomes related to these issues in practice (considering feasibility and cost) will critically accelerate the field of cardio-oncology in the 21st century. With tangible goals, we can improve health inequities in cardio-oncology,” the writing group said.

The research had no commercial funding. No conflicts of interest were reported.

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

A new scientific statement from the American Heart Association focuses on equity in cardio-oncology care and research.

A “growing body of evidence” suggests that women and people from underrepresented patient groups experience disproportionately higher cardiovascular effects from new and emerging anticancer therapies, the writing group, led by Daniel Addison, MD, with the Ohio State University, Columbus, pointed out.

For example, women appear to be at higher risk of immune checkpoint inhibitor–related toxicities, whereas Black patients with cancer face up to a threefold higher risk of cardiotoxicity with anticancer therapies.

With reduced screening and delayed preventive measures, Hispanic patients have more complex heart disease, cancer is diagnosed at later stages, and they receive more cardiotoxic regimens because of a lack of eligibility for novel treatments. Ultimately, this contributes to a higher incidence of treatment complications, cardiac dysfunction, and adverse patient outcomes for this patient group, they write.

Although no studies have specifically addressed cardio-oncology disparities in the LGBTQIA+ population, such disparities can be inferred from known cardiovascular disease and oncology disparities, the writing group noted.

These disparities are supported by “disparately high” risk of death after a cancer diagnosis among women and individuals from underrepresented groups, even after accounting for socioeconomic and behavioral patterns, they pointed out.

The scientific statement was published online in Circulation.
 

Evidence gaps and the path forward

“Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations,” the writing group said.

Decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigations, and potential optimal strategies to address disparate cardiotoxicity with contemporary cancer immunotherapy, as well as biologic and cytotoxic therapies, they noted.

They said caution is needed when interpreting clinical trial data about cardiotoxicity and in generalizing the results because people from diverse racial and ethnic groups have not been well represented in many trials.

The writing group outlined key evidence gaps and future research directions for addressing cardio-oncology disparities, as well as strategies to improve equity in cardio-oncology care and research.

These include the following:

• Identifying specific predictive factors of long-term cardiotoxic risk with targeted and immune-based cancer therapies in women and underrepresented populations.
• Investigating biological mechanisms that may underlie differences in cardiotoxicities between different patient groups.
• Developing personalized cardioprotection strategies that integrate biological, genetic, and social determinant markers.
• Intentionally diversifying clinical trials and identifying optimal strategies to improve representation in cancer clinical trials.
• Determining the role of technology, such as artificial intelligence, in improving cardiotoxicity disparities.

“Conscientiously leveraging technology and designing trials with outcomes related to these issues in practice (considering feasibility and cost) will critically accelerate the field of cardio-oncology in the 21st century. With tangible goals, we can improve health inequities in cardio-oncology,” the writing group said.

The research had no commercial funding. No conflicts of interest were reported.

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

Teenagers with diabetes who use a continuous glucose monitor (CGM) employ a wide variety of alarm settings to alert them when their blood sugar may be too high or too low. But sometimes those thresholds generate too many alarms – which in turn might lead patients to ignore the devices, according to a study presented at the 2023 annual meeting of the Endocrine Society.

“These alarms alert people with diabetes and their caregivers of pending glycemic changes. However, little work has been done studying CGM alarm settings in pediatric clinical populations,” said Victoria Ochs, BS, a medical student at the Indiana University, Indianapolis, who helped conduct the study.

Ms. Ochs and colleagues analyzed 2 weeks of real-time CGM alarm settings from 150 children with diabetes treated at Indiana. Their average age was 14 years; 47% were female, 89% of were White, 9.5% were Black, and 1.5% were Asian. Approximately half the patients used insulin pumps (51%) in addition to the monitoring devices.  

For both alarms that indicated blood sugar was too low or too high, settings among the children often varied widely from thresholds recommended by the University of Colorado’s Barbara Davis Center for Diabetes, Aurora. Those thresholds are 70 mg/dL of glucose for low and 180 mg/dL for high glucose. At Indiana, the median alert level for low was set to 74 mg/dL (range: 60-100), while the median for high was 242 mg/dL (range: 120-400). 

“If we have it set at 100, what exactly is the purpose of that? Is it just to make you more anxious that you’re going to drop low at some point?” asked Cari Berget, MPH, RN, CDE, who specializes in pediatric diabetes at the University of Colorado, speaking of the low blood sugar alarm. Setting this alarm at 70 md/dL instead could lead to concrete action when it does go off – such as consuming carbohydrates to boost blood sugar, she said. 

“Alarms should result in action most of the time,” said Ms. Berget, associate director of Colorado’s PANTHER program, which established the alarm thresholds used in the Indiana study. Alarm setting is not one-size-fits-all, Ms. Berget noted: Some people might want 70 mg/dL to warn of low blood sugar, whereas others prefer 75 or 80 mg/dL. 

As for alerts about hyperglycemia, Ms. Berget said patients often exceed the high range of 180 mg/dL immediately after a meal. Ideally these sugars will subside on their own within 3 hours, a process aided by insulin shots or pumps. Setting a threshold for high blood sugar too low, such as 120 mg/dL, could result in ceaseless alarms even if the person is not at risk for harm.

“If you receive an alarm and there’s no action for you to take, then we need to change how we’re setting these alarms,” Ms. Berget said. She advised parents and children to be thoughtful about setting their CGM alarm thresholds to be most useful to them.

Ms. Ochs said in some cases families have CGM devices shipped directly to their homes and never consult with anyone about optimal alarm settings.

“It would be useful to talk to families about what baseline information they had,” Ms. Ochs told this news organization. “It would be nice to talk to diabetes educators, and I think it would be nice to talk to physicians.”

Ms. Ochs reports no relevant financial relationships. Ms. Berget has consulted for Dexcom and Insulet.
 

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

Teenagers with diabetes who use a continuous glucose monitor (CGM) employ a wide variety of alarm settings to alert them when their blood sugar may be too high or too low. But sometimes those thresholds generate too many alarms – which in turn might lead patients to ignore the devices, according to a study presented at the 2023 annual meeting of the Endocrine Society.

“These alarms alert people with diabetes and their caregivers of pending glycemic changes. However, little work has been done studying CGM alarm settings in pediatric clinical populations,” said Victoria Ochs, BS, a medical student at the Indiana University, Indianapolis, who helped conduct the study.

Ms. Ochs and colleagues analyzed 2 weeks of real-time CGM alarm settings from 150 children with diabetes treated at Indiana. Their average age was 14 years; 47% were female, 89% of were White, 9.5% were Black, and 1.5% were Asian. Approximately half the patients used insulin pumps (51%) in addition to the monitoring devices.  

For both alarms that indicated blood sugar was too low or too high, settings among the children often varied widely from thresholds recommended by the University of Colorado’s Barbara Davis Center for Diabetes, Aurora. Those thresholds are 70 mg/dL of glucose for low and 180 mg/dL for high glucose. At Indiana, the median alert level for low was set to 74 mg/dL (range: 60-100), while the median for high was 242 mg/dL (range: 120-400). 

“If we have it set at 100, what exactly is the purpose of that? Is it just to make you more anxious that you’re going to drop low at some point?” asked Cari Berget, MPH, RN, CDE, who specializes in pediatric diabetes at the University of Colorado, speaking of the low blood sugar alarm. Setting this alarm at 70 md/dL instead could lead to concrete action when it does go off – such as consuming carbohydrates to boost blood sugar, she said. 

“Alarms should result in action most of the time,” said Ms. Berget, associate director of Colorado’s PANTHER program, which established the alarm thresholds used in the Indiana study. Alarm setting is not one-size-fits-all, Ms. Berget noted: Some people might want 70 mg/dL to warn of low blood sugar, whereas others prefer 75 or 80 mg/dL. 

As for alerts about hyperglycemia, Ms. Berget said patients often exceed the high range of 180 mg/dL immediately after a meal. Ideally these sugars will subside on their own within 3 hours, a process aided by insulin shots or pumps. Setting a threshold for high blood sugar too low, such as 120 mg/dL, could result in ceaseless alarms even if the person is not at risk for harm.

“If you receive an alarm and there’s no action for you to take, then we need to change how we’re setting these alarms,” Ms. Berget said. She advised parents and children to be thoughtful about setting their CGM alarm thresholds to be most useful to them.

Ms. Ochs said in some cases families have CGM devices shipped directly to their homes and never consult with anyone about optimal alarm settings.

“It would be useful to talk to families about what baseline information they had,” Ms. Ochs told this news organization. “It would be nice to talk to diabetes educators, and I think it would be nice to talk to physicians.”

Ms. Ochs reports no relevant financial relationships. Ms. Berget has consulted for Dexcom and Insulet.
 

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

Teenagers with diabetes who use a continuous glucose monitor (CGM) employ a wide variety of alarm settings to alert them when their blood sugar may be too high or too low. But sometimes those thresholds generate too many alarms – which in turn might lead patients to ignore the devices, according to a study presented at the 2023 annual meeting of the Endocrine Society.

“These alarms alert people with diabetes and their caregivers of pending glycemic changes. However, little work has been done studying CGM alarm settings in pediatric clinical populations,” said Victoria Ochs, BS, a medical student at the Indiana University, Indianapolis, who helped conduct the study.

Ms. Ochs and colleagues analyzed 2 weeks of real-time CGM alarm settings from 150 children with diabetes treated at Indiana. Their average age was 14 years; 47% were female, 89% of were White, 9.5% were Black, and 1.5% were Asian. Approximately half the patients used insulin pumps (51%) in addition to the monitoring devices.  

For both alarms that indicated blood sugar was too low or too high, settings among the children often varied widely from thresholds recommended by the University of Colorado’s Barbara Davis Center for Diabetes, Aurora. Those thresholds are 70 mg/dL of glucose for low and 180 mg/dL for high glucose. At Indiana, the median alert level for low was set to 74 mg/dL (range: 60-100), while the median for high was 242 mg/dL (range: 120-400). 

“If we have it set at 100, what exactly is the purpose of that? Is it just to make you more anxious that you’re going to drop low at some point?” asked Cari Berget, MPH, RN, CDE, who specializes in pediatric diabetes at the University of Colorado, speaking of the low blood sugar alarm. Setting this alarm at 70 md/dL instead could lead to concrete action when it does go off – such as consuming carbohydrates to boost blood sugar, she said. 

“Alarms should result in action most of the time,” said Ms. Berget, associate director of Colorado’s PANTHER program, which established the alarm thresholds used in the Indiana study. Alarm setting is not one-size-fits-all, Ms. Berget noted: Some people might want 70 mg/dL to warn of low blood sugar, whereas others prefer 75 or 80 mg/dL. 

As for alerts about hyperglycemia, Ms. Berget said patients often exceed the high range of 180 mg/dL immediately after a meal. Ideally these sugars will subside on their own within 3 hours, a process aided by insulin shots or pumps. Setting a threshold for high blood sugar too low, such as 120 mg/dL, could result in ceaseless alarms even if the person is not at risk for harm.

“If you receive an alarm and there’s no action for you to take, then we need to change how we’re setting these alarms,” Ms. Berget said. She advised parents and children to be thoughtful about setting their CGM alarm thresholds to be most useful to them.

Ms. Ochs said in some cases families have CGM devices shipped directly to their homes and never consult with anyone about optimal alarm settings.

“It would be useful to talk to families about what baseline information they had,” Ms. Ochs told this news organization. “It would be nice to talk to diabetes educators, and I think it would be nice to talk to physicians.”

Ms. Ochs reports no relevant financial relationships. Ms. Berget has consulted for Dexcom and Insulet.
 

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

Continuing anticoagulation indefinitely in patients with a first unprovoked venous thromboembolism (VTE) may have benefits for certain patients but is unlikely to be cost effective, say authors of a new study.

Continued anticoagulation for such patients “has little chance of improving life expectancy but might provide a mortality benefit in certain subgroups including patients with an initial PE (pulmonary embolism) or those at a very low risk for major bleeding,” wrote the authors, led by Faizan Khan, PhD, with the O’Brien Institute for Public Health, University of Calgary (Alta.).

Therefore, shared decision-making between patients with unprovoked VTE and physicians that includes discussion of preferences and values and use of validated prediction tools is important.

The authors noted that some patients might value avoiding morbidities of recurrent VTE the most and want to have lifelong anticoagulation. Some might be more fearful of major bleeding than VTE repercussions or don’t want the inconveniences of taking anticoagulants for a lifetime.

The findings were published in Annals of Internal Medicine.
 

Current guidelines recommend indefinite anticoagulation

Clinical practice guidelines now recommend indefinite anticoagulation for a first unprovoked VTE.

The authors did a modeling study in a hypothetical cohort of 1,000 patients aged 55 years with a first unprovoked VTE who had completed 3-6 months of initial anticoagulation. The study found indefinite anticoagulation, compared with discontinuing anticoagulation, on average, resulted in 368 fewer recurrent VTE events and 14 fewer fatal PE events.

At the same time, indefinite coagulation in the hypothetical group induced an additional 114 major bleeding events, 30 intracerebral hemorrhages, and 11 fatal bleeding events over 40 years.

As for cost effectiveness, from the perspective of Canada’s health care system, continuing anticoagulation indefinitely, on average, increased costs by $16,014 Canadian dollars per person ($12,140 USD) without improving quality-adjusted life-years (incremental difference, 0.075 per person; 95% uncertainty interval, –0.192 to 0.017).

The authors noted that cost is a prime consideration as the estimated annual health care costs of VTE and its complications is $600 Canadian dollars ($7 billion–$10 billion USD).
 

High probability of small benefit

The authors spelled out the small benefit in patients with an initial PE.

According to the study, indefinite anticoagulation would result in an 80% probability of a marginal added clinical benefit (average increase of 57 days of perfect health over a lifetime) in patients with an initial PE (but with only a 24% chance of being cost effective).

“This high probability of an additional clinical benefit is plausible due to the higher proportion of recurrent VTE events presenting as PE (approximately 70% of episodes) in patients initially presenting with PE, in turn, resulting in a two- to threefold higher case-fatality rate of recurrent VTE in this patient subgroup.”
 

Tools to estimate bleeding risk imprecise

Scott Woller, MD, an internal medicine specialist and chair of medicine at Intermountain Medical Center, Murray, Utah, said in an interview that these results should help physicians’ discuss with their patients about duration of anticoagulation after the treatment phase.

He noted that the authors suggest that a low estimated annual risk for major bleeding should be assumed (< 0.67%) to make the choice for indefinite anticoagulation.

“This is a sticky wicket,” he said, “as tools to estimate bleeding risk among VTE patients are presently imprecise. For these reasons PCPs should take into account patient risk estimates – and the limitations that exist surrounding how we calculate these estimates – in addition to their values and preferences. This is really key in electing duration of anticoagulation.” 

A limitation of the study is that the model assumed that risks for recurrent VTE and major bleeding in clinical trials at 1 year remained constant during extended anticoagulation.

Dr. Woller said about that limitation: “One might argue that this is unlikely; age is a risk factor for major bleeding and therefore risks may be underestimated. However, in the ‘real world’ those that are perceived at lowest risk and demonstrate good tolerance to anticoagulation might likely preferentially continue anticoagulants and therefore risks may be overestimated.”

One coauthor reported being a clinical investigator for trials sponsored by Pfizer and Bristol-Myers Squibb and receiving honoraria from Pfizer, Sanofi and Aspen Pharma. The other authors disclosed no other relevant financial relationships. Dr. Woller is cochair of the CHEST guidelines on the treatment of venous thromboembolic disease.

Continuing anticoagulation indefinitely in patients with a first unprovoked venous thromboembolism (VTE) may have benefits for certain patients but is unlikely to be cost effective, say authors of a new study.

Continued anticoagulation for such patients “has little chance of improving life expectancy but might provide a mortality benefit in certain subgroups including patients with an initial PE (pulmonary embolism) or those at a very low risk for major bleeding,” wrote the authors, led by Faizan Khan, PhD, with the O’Brien Institute for Public Health, University of Calgary (Alta.).

Therefore, shared decision-making between patients with unprovoked VTE and physicians that includes discussion of preferences and values and use of validated prediction tools is important.

The authors noted that some patients might value avoiding morbidities of recurrent VTE the most and want to have lifelong anticoagulation. Some might be more fearful of major bleeding than VTE repercussions or don’t want the inconveniences of taking anticoagulants for a lifetime.

The findings were published in Annals of Internal Medicine.
 

Current guidelines recommend indefinite anticoagulation

Clinical practice guidelines now recommend indefinite anticoagulation for a first unprovoked VTE.

The authors did a modeling study in a hypothetical cohort of 1,000 patients aged 55 years with a first unprovoked VTE who had completed 3-6 months of initial anticoagulation. The study found indefinite anticoagulation, compared with discontinuing anticoagulation, on average, resulted in 368 fewer recurrent VTE events and 14 fewer fatal PE events.

At the same time, indefinite coagulation in the hypothetical group induced an additional 114 major bleeding events, 30 intracerebral hemorrhages, and 11 fatal bleeding events over 40 years.

As for cost effectiveness, from the perspective of Canada’s health care system, continuing anticoagulation indefinitely, on average, increased costs by $16,014 Canadian dollars per person ($12,140 USD) without improving quality-adjusted life-years (incremental difference, 0.075 per person; 95% uncertainty interval, –0.192 to 0.017).

The authors noted that cost is a prime consideration as the estimated annual health care costs of VTE and its complications is $600 Canadian dollars ($7 billion–$10 billion USD).
 

High probability of small benefit

The authors spelled out the small benefit in patients with an initial PE.

According to the study, indefinite anticoagulation would result in an 80% probability of a marginal added clinical benefit (average increase of 57 days of perfect health over a lifetime) in patients with an initial PE (but with only a 24% chance of being cost effective).

“This high probability of an additional clinical benefit is plausible due to the higher proportion of recurrent VTE events presenting as PE (approximately 70% of episodes) in patients initially presenting with PE, in turn, resulting in a two- to threefold higher case-fatality rate of recurrent VTE in this patient subgroup.”
 

Tools to estimate bleeding risk imprecise

Scott Woller, MD, an internal medicine specialist and chair of medicine at Intermountain Medical Center, Murray, Utah, said in an interview that these results should help physicians’ discuss with their patients about duration of anticoagulation after the treatment phase.

He noted that the authors suggest that a low estimated annual risk for major bleeding should be assumed (< 0.67%) to make the choice for indefinite anticoagulation.

“This is a sticky wicket,” he said, “as tools to estimate bleeding risk among VTE patients are presently imprecise. For these reasons PCPs should take into account patient risk estimates – and the limitations that exist surrounding how we calculate these estimates – in addition to their values and preferences. This is really key in electing duration of anticoagulation.” 

A limitation of the study is that the model assumed that risks for recurrent VTE and major bleeding in clinical trials at 1 year remained constant during extended anticoagulation.

Dr. Woller said about that limitation: “One might argue that this is unlikely; age is a risk factor for major bleeding and therefore risks may be underestimated. However, in the ‘real world’ those that are perceived at lowest risk and demonstrate good tolerance to anticoagulation might likely preferentially continue anticoagulants and therefore risks may be overestimated.”

One coauthor reported being a clinical investigator for trials sponsored by Pfizer and Bristol-Myers Squibb and receiving honoraria from Pfizer, Sanofi and Aspen Pharma. The other authors disclosed no other relevant financial relationships. Dr. Woller is cochair of the CHEST guidelines on the treatment of venous thromboembolic disease.

Continuing anticoagulation indefinitely in patients with a first unprovoked venous thromboembolism (VTE) may have benefits for certain patients but is unlikely to be cost effective, say authors of a new study.

Continued anticoagulation for such patients “has little chance of improving life expectancy but might provide a mortality benefit in certain subgroups including patients with an initial PE (pulmonary embolism) or those at a very low risk for major bleeding,” wrote the authors, led by Faizan Khan, PhD, with the O’Brien Institute for Public Health, University of Calgary (Alta.).

Therefore, shared decision-making between patients with unprovoked VTE and physicians that includes discussion of preferences and values and use of validated prediction tools is important.

The authors noted that some patients might value avoiding morbidities of recurrent VTE the most and want to have lifelong anticoagulation. Some might be more fearful of major bleeding than VTE repercussions or don’t want the inconveniences of taking anticoagulants for a lifetime.

The findings were published in Annals of Internal Medicine.
 

Current guidelines recommend indefinite anticoagulation

Clinical practice guidelines now recommend indefinite anticoagulation for a first unprovoked VTE.

The authors did a modeling study in a hypothetical cohort of 1,000 patients aged 55 years with a first unprovoked VTE who had completed 3-6 months of initial anticoagulation. The study found indefinite anticoagulation, compared with discontinuing anticoagulation, on average, resulted in 368 fewer recurrent VTE events and 14 fewer fatal PE events.

At the same time, indefinite coagulation in the hypothetical group induced an additional 114 major bleeding events, 30 intracerebral hemorrhages, and 11 fatal bleeding events over 40 years.

As for cost effectiveness, from the perspective of Canada’s health care system, continuing anticoagulation indefinitely, on average, increased costs by $16,014 Canadian dollars per person ($12,140 USD) without improving quality-adjusted life-years (incremental difference, 0.075 per person; 95% uncertainty interval, –0.192 to 0.017).

The authors noted that cost is a prime consideration as the estimated annual health care costs of VTE and its complications is $600 Canadian dollars ($7 billion–$10 billion USD).
 

High probability of small benefit

The authors spelled out the small benefit in patients with an initial PE.

According to the study, indefinite anticoagulation would result in an 80% probability of a marginal added clinical benefit (average increase of 57 days of perfect health over a lifetime) in patients with an initial PE (but with only a 24% chance of being cost effective).

“This high probability of an additional clinical benefit is plausible due to the higher proportion of recurrent VTE events presenting as PE (approximately 70% of episodes) in patients initially presenting with PE, in turn, resulting in a two- to threefold higher case-fatality rate of recurrent VTE in this patient subgroup.”
 

Tools to estimate bleeding risk imprecise

Scott Woller, MD, an internal medicine specialist and chair of medicine at Intermountain Medical Center, Murray, Utah, said in an interview that these results should help physicians’ discuss with their patients about duration of anticoagulation after the treatment phase.

He noted that the authors suggest that a low estimated annual risk for major bleeding should be assumed (< 0.67%) to make the choice for indefinite anticoagulation.

“This is a sticky wicket,” he said, “as tools to estimate bleeding risk among VTE patients are presently imprecise. For these reasons PCPs should take into account patient risk estimates – and the limitations that exist surrounding how we calculate these estimates – in addition to their values and preferences. This is really key in electing duration of anticoagulation.” 

A limitation of the study is that the model assumed that risks for recurrent VTE and major bleeding in clinical trials at 1 year remained constant during extended anticoagulation.

Dr. Woller said about that limitation: “One might argue that this is unlikely; age is a risk factor for major bleeding and therefore risks may be underestimated. However, in the ‘real world’ those that are perceived at lowest risk and demonstrate good tolerance to anticoagulation might likely preferentially continue anticoagulants and therefore risks may be overestimated.”

One coauthor reported being a clinical investigator for trials sponsored by Pfizer and Bristol-Myers Squibb and receiving honoraria from Pfizer, Sanofi and Aspen Pharma. The other authors disclosed no other relevant financial relationships. Dr. Woller is cochair of the CHEST guidelines on the treatment of venous thromboembolic disease.

Patients with head and neck cancer and overweight saw better treatment response and survival after chemoradiation, compared with patients with the same type of cancer but a normal weight, a new study finds.

The findings, published in JAMA Network Open, are the latest to parse the complex relationship between body mass index (BMI) and treatment in cancers that is sometimes called the “obesity paradox.” The researchers compared outcomes among patients with normal weight, overweight, and obesity.

While higher BMI is an established risk factor for many types of cancer and for cancer-specific mortality overall, studies in some cancers have shown that patients with higher BMI do better, possibly because excess BMI acts as a nutrient reserve against treatment-associated weight loss.
 

Methods and results

For their research, Sung Jun Ma, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues looked at records for 445 patients (84% men, median age 61) at Dr. Ma’s institution with nonmetastatic head and neck cancer who underwent chemoradiotherapy between 2005 and 2021. Patients were followed up for a median 48 months, and those with underweight at treatment initiation were excluded.

The researchers found that overweight BMI (25-29.9 kg/m²) was associated with improved overall survival at 5 years (71% vs. 58% of patients with normal weight), as well as 5-year progression-free survival (68% vs. 51%). No overall or progression-free survival benefit link was seen in patients with a BMI of 30 or higher, in contrast to some previous studies of patients with head and neck cancers. BMI was not associated with improved survival outcomes among human papillomavirus–positive patients.

Both overweight and obesity were associated with complete response on follow-up PET-CT, with nearly 92% of patients with overweight and 91% of patients with obesity (defined as having a BMI of 30 or higher) seeing a complete metabolic response, compared with 74% of patients with normal weight.

Having an overweight BMI was also associated with improvements in tumor recurrence, with fewer of patients with this type of BMI experiencing 5-year locoregional failure than patients with normal weight (7% vs 26%). Having an obese BMI was not associated with improvements in recurrence. All the reported differences reached statistical significance.

The study authors surmised that the discrepancies between outcomes for patients with overweight and obesity “may be due to a nonlinear association between BMI and survival, with the highest survival seen in the overweight BMI range.”

It was important to note that this study saw no differences in treatment interruptions between the BMI groups that could account for differences in outcomes. Only three patients in the cohort saw their radiotherapy treatment interrupted, Dr. Ma said in an interview.

“If we felt that the obesity paradox happens because people with normal BMI lose too much weight during the treatment course, treatment gets interrupted, and they get worse outcomes from suboptimal treatments, then we would have seen more treatment interruptions among those with normal BMI. However, that was not the case in our study,” he said. Rather, the results point to “a complex interaction among cancer, [a person’s build], and nutritional status.”

Clinicians should be aware, Dr. Ma added, “that the same head and neck cancer may behave more aggressively among patients with normal BMI, compared to others with overweight BMI. Patients with normal BMI may need to be monitored more closely and carefully for potentially worse outcomes.” 

The investigators acknowledged several weaknesses of their study, including its retrospective design, the measure of BMI using cutoffs rather than a continuum, and the collection of BMI information at a single time point. While 84% of patients in the study received cisplatin, the study did not contain information on cumulative cisplatin dose.
 

Importance of nutritional support during treatment highlighted

In an interview, Ari Rosenberg, MD, of the University of Chicago Medicine, commented that the findings highlighted the importance of expert nutritional supportive care during treatment and monitoring for patients with advanced head and neck cancers undergoing chemoradiation.

“Nutritional status is very important both at baseline and during treatment,” Dr. Rosenberg said. “Even small changes in weight or BMI can be a key indicator of supportive care during chemoradiation and represent a biomarker to guide supportive management. ... The take home message is that patients should be treated at centers that have a high volume of advanced head and neck cancer patients, which have all the supportive components and expertise to optimize treatment delivery and maximize survival.”

Dr. Ma and colleagues’ study was funded by the National Cancer Institute Cancer Center. None of its authors declared financial conflicts of interest. Dr. Rosenberg disclosed receiving consulting fees from EMD Serono related to head and neck cancer treatment.
 

Patients with head and neck cancer and overweight saw better treatment response and survival after chemoradiation, compared with patients with the same type of cancer but a normal weight, a new study finds.

The findings, published in JAMA Network Open, are the latest to parse the complex relationship between body mass index (BMI) and treatment in cancers that is sometimes called the “obesity paradox.” The researchers compared outcomes among patients with normal weight, overweight, and obesity.

While higher BMI is an established risk factor for many types of cancer and for cancer-specific mortality overall, studies in some cancers have shown that patients with higher BMI do better, possibly because excess BMI acts as a nutrient reserve against treatment-associated weight loss.
 

Methods and results

For their research, Sung Jun Ma, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues looked at records for 445 patients (84% men, median age 61) at Dr. Ma’s institution with nonmetastatic head and neck cancer who underwent chemoradiotherapy between 2005 and 2021. Patients were followed up for a median 48 months, and those with underweight at treatment initiation were excluded.

The researchers found that overweight BMI (25-29.9 kg/m²) was associated with improved overall survival at 5 years (71% vs. 58% of patients with normal weight), as well as 5-year progression-free survival (68% vs. 51%). No overall or progression-free survival benefit link was seen in patients with a BMI of 30 or higher, in contrast to some previous studies of patients with head and neck cancers. BMI was not associated with improved survival outcomes among human papillomavirus–positive patients.

Both overweight and obesity were associated with complete response on follow-up PET-CT, with nearly 92% of patients with overweight and 91% of patients with obesity (defined as having a BMI of 30 or higher) seeing a complete metabolic response, compared with 74% of patients with normal weight.

Having an overweight BMI was also associated with improvements in tumor recurrence, with fewer of patients with this type of BMI experiencing 5-year locoregional failure than patients with normal weight (7% vs 26%). Having an obese BMI was not associated with improvements in recurrence. All the reported differences reached statistical significance.

The study authors surmised that the discrepancies between outcomes for patients with overweight and obesity “may be due to a nonlinear association between BMI and survival, with the highest survival seen in the overweight BMI range.”

It was important to note that this study saw no differences in treatment interruptions between the BMI groups that could account for differences in outcomes. Only three patients in the cohort saw their radiotherapy treatment interrupted, Dr. Ma said in an interview.

“If we felt that the obesity paradox happens because people with normal BMI lose too much weight during the treatment course, treatment gets interrupted, and they get worse outcomes from suboptimal treatments, then we would have seen more treatment interruptions among those with normal BMI. However, that was not the case in our study,” he said. Rather, the results point to “a complex interaction among cancer, [a person’s build], and nutritional status.”

Clinicians should be aware, Dr. Ma added, “that the same head and neck cancer may behave more aggressively among patients with normal BMI, compared to others with overweight BMI. Patients with normal BMI may need to be monitored more closely and carefully for potentially worse outcomes.” 

The investigators acknowledged several weaknesses of their study, including its retrospective design, the measure of BMI using cutoffs rather than a continuum, and the collection of BMI information at a single time point. While 84% of patients in the study received cisplatin, the study did not contain information on cumulative cisplatin dose.
 

Importance of nutritional support during treatment highlighted

In an interview, Ari Rosenberg, MD, of the University of Chicago Medicine, commented that the findings highlighted the importance of expert nutritional supportive care during treatment and monitoring for patients with advanced head and neck cancers undergoing chemoradiation.

“Nutritional status is very important both at baseline and during treatment,” Dr. Rosenberg said. “Even small changes in weight or BMI can be a key indicator of supportive care during chemoradiation and represent a biomarker to guide supportive management. ... The take home message is that patients should be treated at centers that have a high volume of advanced head and neck cancer patients, which have all the supportive components and expertise to optimize treatment delivery and maximize survival.”

Dr. Ma and colleagues’ study was funded by the National Cancer Institute Cancer Center. None of its authors declared financial conflicts of interest. Dr. Rosenberg disclosed receiving consulting fees from EMD Serono related to head and neck cancer treatment.
 

Patients with head and neck cancer and overweight saw better treatment response and survival after chemoradiation, compared with patients with the same type of cancer but a normal weight, a new study finds.

The findings, published in JAMA Network Open, are the latest to parse the complex relationship between body mass index (BMI) and treatment in cancers that is sometimes called the “obesity paradox.” The researchers compared outcomes among patients with normal weight, overweight, and obesity.

While higher BMI is an established risk factor for many types of cancer and for cancer-specific mortality overall, studies in some cancers have shown that patients with higher BMI do better, possibly because excess BMI acts as a nutrient reserve against treatment-associated weight loss.
 

Methods and results

For their research, Sung Jun Ma, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues looked at records for 445 patients (84% men, median age 61) at Dr. Ma’s institution with nonmetastatic head and neck cancer who underwent chemoradiotherapy between 2005 and 2021. Patients were followed up for a median 48 months, and those with underweight at treatment initiation were excluded.

The researchers found that overweight BMI (25-29.9 kg/m²) was associated with improved overall survival at 5 years (71% vs. 58% of patients with normal weight), as well as 5-year progression-free survival (68% vs. 51%). No overall or progression-free survival benefit link was seen in patients with a BMI of 30 or higher, in contrast to some previous studies of patients with head and neck cancers. BMI was not associated with improved survival outcomes among human papillomavirus–positive patients.

Both overweight and obesity were associated with complete response on follow-up PET-CT, with nearly 92% of patients with overweight and 91% of patients with obesity (defined as having a BMI of 30 or higher) seeing a complete metabolic response, compared with 74% of patients with normal weight.

Having an overweight BMI was also associated with improvements in tumor recurrence, with fewer of patients with this type of BMI experiencing 5-year locoregional failure than patients with normal weight (7% vs 26%). Having an obese BMI was not associated with improvements in recurrence. All the reported differences reached statistical significance.

The study authors surmised that the discrepancies between outcomes for patients with overweight and obesity “may be due to a nonlinear association between BMI and survival, with the highest survival seen in the overweight BMI range.”

It was important to note that this study saw no differences in treatment interruptions between the BMI groups that could account for differences in outcomes. Only three patients in the cohort saw their radiotherapy treatment interrupted, Dr. Ma said in an interview.

“If we felt that the obesity paradox happens because people with normal BMI lose too much weight during the treatment course, treatment gets interrupted, and they get worse outcomes from suboptimal treatments, then we would have seen more treatment interruptions among those with normal BMI. However, that was not the case in our study,” he said. Rather, the results point to “a complex interaction among cancer, [a person’s build], and nutritional status.”

Clinicians should be aware, Dr. Ma added, “that the same head and neck cancer may behave more aggressively among patients with normal BMI, compared to others with overweight BMI. Patients with normal BMI may need to be monitored more closely and carefully for potentially worse outcomes.” 

The investigators acknowledged several weaknesses of their study, including its retrospective design, the measure of BMI using cutoffs rather than a continuum, and the collection of BMI information at a single time point. While 84% of patients in the study received cisplatin, the study did not contain information on cumulative cisplatin dose.
 

Importance of nutritional support during treatment highlighted

In an interview, Ari Rosenberg, MD, of the University of Chicago Medicine, commented that the findings highlighted the importance of expert nutritional supportive care during treatment and monitoring for patients with advanced head and neck cancers undergoing chemoradiation.

“Nutritional status is very important both at baseline and during treatment,” Dr. Rosenberg said. “Even small changes in weight or BMI can be a key indicator of supportive care during chemoradiation and represent a biomarker to guide supportive management. ... The take home message is that patients should be treated at centers that have a high volume of advanced head and neck cancer patients, which have all the supportive components and expertise to optimize treatment delivery and maximize survival.”

Dr. Ma and colleagues’ study was funded by the National Cancer Institute Cancer Center. None of its authors declared financial conflicts of interest. Dr. Rosenberg disclosed receiving consulting fees from EMD Serono related to head and neck cancer treatment.
 

In the absence of a formal diagnostic test for Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the current approach employed by most clinicians tends to overlabel patients as allergic to drugs that are unlikely to be the cause, results from a small retrospective cohort study demonstrated.

“Prompt identification and discontinuation of a culprit drug is critical to improving patient outcomes and preventing recurrence,” researchers led by Sherrie J. Divito, MD, PhD, of the department of dermatology at Brigham and Women’s Hospital, Boston, wrote in the study, which was published online in JAMA Dermatology. “Identification is difficult because there is no laboratory test or other criterion standard (in the absence of rechallenge) to identify a culprit drug, and patients take on average six medications at the time of their reaction. Consequently, many patients may be labeled as allergic to multiple agents.”

Although failing to identify the culprit drug can have severe consequences, they added, “overlabeling” (labeling a patient as allergic to a drug or drugs that they can tolerate safely) “is not insignificant.” As a result of overlabeling, “the patient may receive a less efficacious, more toxic, and/or more expensive agent than necessary, and in some cases may be left without treatment for their underlying disease.”

To evaluate the outcomes of patients’ allergy lists, current approaches to identify culprit drugs such as the Algorithm for Drug Causality for Epidermal Necrolysis (ALDEN), which was published in 2010, and potential methods of improving culprit drug identification, the researchers performed a retrospective cohort study of 48 patients at Brigham and Women’s Hospital and Massachusetts General Hospital, with clinically and histologically confirmed cases of SJS/TEN between January 2000 and July 2018. Of the 48 patients, 26 had SJS/TEN overlap and 22 had TEN. Their median age at diagnosis was 40 years; 60.4% were female; and 52.1% were white, 12.5% were Black, 10.4% were Hispanic, and 8.3% were Asian. They took a median of 6.5 drugs in the 3 months prior to disease onset.

The researchers observed that all patients had at least one drug labeled as an allergy. A single culprit drug was labeled in 17 cases, but physicians communicated certainty in only 7 of those cases. Among all 48 patients, 104 drugs were labeled as allergies.

To identify a culprit drug, physicians appeared to mainly rely on two factors: drug notoriety and timing of exposure, compared with the onset of SJS/TEN. “Identifying high-risk medications seemed heuristic, with one or more drugs in question noted in the record as a common culprit without reference to published or vetted data regarding risk,” the researchers wrote. “Regarding timing, drug charts when present in medical records were incomplete, as they focused predominantly on high-notoriety drugs.”

In other findings, ALDEN scoring was discordant with physician-labeled lists in 28 cases. It labeled an additional 9 drugs missed by physicians and scored 43 drugs labeled as allergens by physicians as “unlikely.” The researchers also reported that 20 cases could have potentially benefited from human leukocyte antigen testing.

Their results “underscore the need for a laboratory test to identify culprit drugs,” but without such a test, “a systematic unbiased approach, such as ALDEN or the RegiSCAR database, with possibly HLA testing, should be considered to ensure the true culprit drug is not missed and exonerate as many nonculprit drugs as possible,” Dr. Divito and colleagues concluded.

They acknowledged certain limitations of the analysis, including its retrospective design and that many cases predated research advances in the topic area that took place during the 18-year study period.

Karl Saardi, MD, director of the inpatient dermatology service at George Washington University Hospital, Washington, who was asked to comment on the study, said that the findings “are consistent with clinical practice in that drug causality is usually determined by ‘gestalt’ rather than objective tools like the ALDEN algorithm.”

“The main limitation is the small size, which suggests the study sites are low-volume centers for SJS/TEN. The fact that the ALDEN score wasn’t developed until 2010 means that all the cases included prior to 2010 would not have applied the ALDEN algorithm, so I think the metric about how infrequently ALDEN was applied is not very meaningful.”

Still, he said that he was “surprised” by the number of medications that were added as allergies based on clinical impression, “and I’m glad this article does cast some light on the issue. In my experience, beta-lactam antibiotics are often – incorrectly – deemed to be the cause of SJS/TEN when further review of the patient’s medication history clearly shows they have tolerated these drugs multiple times in the past.”

Since 2000, he added, “our understanding of SJS/TEN has grown substantially including the identification of MIRM [mycoplasma-induced rash and mucositis]/RIME [reactive infections mucocutaneous eruptions] and GBFDE [generalized bullous fixed drug eruption] as mimickers.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was also asked to comment on the study, agreed that a limitation of the study is that it partially preceded development of the unbiased approaches to determining the cause of a medication reaction, such as the ALDEN system. “A strength of this study is the examination of heuristics in dermatology and how they relate to patient safety,” she added.

The study was funded by grants from the National Institutes of Health, a Dermatology Foundation Diversity Research Supplement Award, and by the German Research Foundation. Dr. Divito reported receiving personal fees from Adaptimmune and MEI Pharma and a provisional patent issued from Brigham and Women’s Hospital outside the submitted work. Neither Dr. Saardi nor Dr. Ko reported having relevant disclosures.

In the absence of a formal diagnostic test for Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the current approach employed by most clinicians tends to overlabel patients as allergic to drugs that are unlikely to be the cause, results from a small retrospective cohort study demonstrated.

“Prompt identification and discontinuation of a culprit drug is critical to improving patient outcomes and preventing recurrence,” researchers led by Sherrie J. Divito, MD, PhD, of the department of dermatology at Brigham and Women’s Hospital, Boston, wrote in the study, which was published online in JAMA Dermatology. “Identification is difficult because there is no laboratory test or other criterion standard (in the absence of rechallenge) to identify a culprit drug, and patients take on average six medications at the time of their reaction. Consequently, many patients may be labeled as allergic to multiple agents.”

Although failing to identify the culprit drug can have severe consequences, they added, “overlabeling” (labeling a patient as allergic to a drug or drugs that they can tolerate safely) “is not insignificant.” As a result of overlabeling, “the patient may receive a less efficacious, more toxic, and/or more expensive agent than necessary, and in some cases may be left without treatment for their underlying disease.”

To evaluate the outcomes of patients’ allergy lists, current approaches to identify culprit drugs such as the Algorithm for Drug Causality for Epidermal Necrolysis (ALDEN), which was published in 2010, and potential methods of improving culprit drug identification, the researchers performed a retrospective cohort study of 48 patients at Brigham and Women’s Hospital and Massachusetts General Hospital, with clinically and histologically confirmed cases of SJS/TEN between January 2000 and July 2018. Of the 48 patients, 26 had SJS/TEN overlap and 22 had TEN. Their median age at diagnosis was 40 years; 60.4% were female; and 52.1% were white, 12.5% were Black, 10.4% were Hispanic, and 8.3% were Asian. They took a median of 6.5 drugs in the 3 months prior to disease onset.

The researchers observed that all patients had at least one drug labeled as an allergy. A single culprit drug was labeled in 17 cases, but physicians communicated certainty in only 7 of those cases. Among all 48 patients, 104 drugs were labeled as allergies.

To identify a culprit drug, physicians appeared to mainly rely on two factors: drug notoriety and timing of exposure, compared with the onset of SJS/TEN. “Identifying high-risk medications seemed heuristic, with one or more drugs in question noted in the record as a common culprit without reference to published or vetted data regarding risk,” the researchers wrote. “Regarding timing, drug charts when present in medical records were incomplete, as they focused predominantly on high-notoriety drugs.”

In other findings, ALDEN scoring was discordant with physician-labeled lists in 28 cases. It labeled an additional 9 drugs missed by physicians and scored 43 drugs labeled as allergens by physicians as “unlikely.” The researchers also reported that 20 cases could have potentially benefited from human leukocyte antigen testing.

Their results “underscore the need for a laboratory test to identify culprit drugs,” but without such a test, “a systematic unbiased approach, such as ALDEN or the RegiSCAR database, with possibly HLA testing, should be considered to ensure the true culprit drug is not missed and exonerate as many nonculprit drugs as possible,” Dr. Divito and colleagues concluded.

They acknowledged certain limitations of the analysis, including its retrospective design and that many cases predated research advances in the topic area that took place during the 18-year study period.

Karl Saardi, MD, director of the inpatient dermatology service at George Washington University Hospital, Washington, who was asked to comment on the study, said that the findings “are consistent with clinical practice in that drug causality is usually determined by ‘gestalt’ rather than objective tools like the ALDEN algorithm.”

“The main limitation is the small size, which suggests the study sites are low-volume centers for SJS/TEN. The fact that the ALDEN score wasn’t developed until 2010 means that all the cases included prior to 2010 would not have applied the ALDEN algorithm, so I think the metric about how infrequently ALDEN was applied is not very meaningful.”

Still, he said that he was “surprised” by the number of medications that were added as allergies based on clinical impression, “and I’m glad this article does cast some light on the issue. In my experience, beta-lactam antibiotics are often – incorrectly – deemed to be the cause of SJS/TEN when further review of the patient’s medication history clearly shows they have tolerated these drugs multiple times in the past.”

Since 2000, he added, “our understanding of SJS/TEN has grown substantially including the identification of MIRM [mycoplasma-induced rash and mucositis]/RIME [reactive infections mucocutaneous eruptions] and GBFDE [generalized bullous fixed drug eruption] as mimickers.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was also asked to comment on the study, agreed that a limitation of the study is that it partially preceded development of the unbiased approaches to determining the cause of a medication reaction, such as the ALDEN system. “A strength of this study is the examination of heuristics in dermatology and how they relate to patient safety,” she added.

The study was funded by grants from the National Institutes of Health, a Dermatology Foundation Diversity Research Supplement Award, and by the German Research Foundation. Dr. Divito reported receiving personal fees from Adaptimmune and MEI Pharma and a provisional patent issued from Brigham and Women’s Hospital outside the submitted work. Neither Dr. Saardi nor Dr. Ko reported having relevant disclosures.

In the absence of a formal diagnostic test for Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), the current approach employed by most clinicians tends to overlabel patients as allergic to drugs that are unlikely to be the cause, results from a small retrospective cohort study demonstrated.

“Prompt identification and discontinuation of a culprit drug is critical to improving patient outcomes and preventing recurrence,” researchers led by Sherrie J. Divito, MD, PhD, of the department of dermatology at Brigham and Women’s Hospital, Boston, wrote in the study, which was published online in JAMA Dermatology. “Identification is difficult because there is no laboratory test or other criterion standard (in the absence of rechallenge) to identify a culprit drug, and patients take on average six medications at the time of their reaction. Consequently, many patients may be labeled as allergic to multiple agents.”

Although failing to identify the culprit drug can have severe consequences, they added, “overlabeling” (labeling a patient as allergic to a drug or drugs that they can tolerate safely) “is not insignificant.” As a result of overlabeling, “the patient may receive a less efficacious, more toxic, and/or more expensive agent than necessary, and in some cases may be left without treatment for their underlying disease.”

To evaluate the outcomes of patients’ allergy lists, current approaches to identify culprit drugs such as the Algorithm for Drug Causality for Epidermal Necrolysis (ALDEN), which was published in 2010, and potential methods of improving culprit drug identification, the researchers performed a retrospective cohort study of 48 patients at Brigham and Women’s Hospital and Massachusetts General Hospital, with clinically and histologically confirmed cases of SJS/TEN between January 2000 and July 2018. Of the 48 patients, 26 had SJS/TEN overlap and 22 had TEN. Their median age at diagnosis was 40 years; 60.4% were female; and 52.1% were white, 12.5% were Black, 10.4% were Hispanic, and 8.3% were Asian. They took a median of 6.5 drugs in the 3 months prior to disease onset.

The researchers observed that all patients had at least one drug labeled as an allergy. A single culprit drug was labeled in 17 cases, but physicians communicated certainty in only 7 of those cases. Among all 48 patients, 104 drugs were labeled as allergies.

To identify a culprit drug, physicians appeared to mainly rely on two factors: drug notoriety and timing of exposure, compared with the onset of SJS/TEN. “Identifying high-risk medications seemed heuristic, with one or more drugs in question noted in the record as a common culprit without reference to published or vetted data regarding risk,” the researchers wrote. “Regarding timing, drug charts when present in medical records were incomplete, as they focused predominantly on high-notoriety drugs.”

In other findings, ALDEN scoring was discordant with physician-labeled lists in 28 cases. It labeled an additional 9 drugs missed by physicians and scored 43 drugs labeled as allergens by physicians as “unlikely.” The researchers also reported that 20 cases could have potentially benefited from human leukocyte antigen testing.

Their results “underscore the need for a laboratory test to identify culprit drugs,” but without such a test, “a systematic unbiased approach, such as ALDEN or the RegiSCAR database, with possibly HLA testing, should be considered to ensure the true culprit drug is not missed and exonerate as many nonculprit drugs as possible,” Dr. Divito and colleagues concluded.

They acknowledged certain limitations of the analysis, including its retrospective design and that many cases predated research advances in the topic area that took place during the 18-year study period.

Karl Saardi, MD, director of the inpatient dermatology service at George Washington University Hospital, Washington, who was asked to comment on the study, said that the findings “are consistent with clinical practice in that drug causality is usually determined by ‘gestalt’ rather than objective tools like the ALDEN algorithm.”

“The main limitation is the small size, which suggests the study sites are low-volume centers for SJS/TEN. The fact that the ALDEN score wasn’t developed until 2010 means that all the cases included prior to 2010 would not have applied the ALDEN algorithm, so I think the metric about how infrequently ALDEN was applied is not very meaningful.”

Still, he said that he was “surprised” by the number of medications that were added as allergies based on clinical impression, “and I’m glad this article does cast some light on the issue. In my experience, beta-lactam antibiotics are often – incorrectly – deemed to be the cause of SJS/TEN when further review of the patient’s medication history clearly shows they have tolerated these drugs multiple times in the past.”

Since 2000, he added, “our understanding of SJS/TEN has grown substantially including the identification of MIRM [mycoplasma-induced rash and mucositis]/RIME [reactive infections mucocutaneous eruptions] and GBFDE [generalized bullous fixed drug eruption] as mimickers.”

Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was also asked to comment on the study, agreed that a limitation of the study is that it partially preceded development of the unbiased approaches to determining the cause of a medication reaction, such as the ALDEN system. “A strength of this study is the examination of heuristics in dermatology and how they relate to patient safety,” she added.

The study was funded by grants from the National Institutes of Health, a Dermatology Foundation Diversity Research Supplement Award, and by the German Research Foundation. Dr. Divito reported receiving personal fees from Adaptimmune and MEI Pharma and a provisional patent issued from Brigham and Women’s Hospital outside the submitted work. Neither Dr. Saardi nor Dr. Ko reported having relevant disclosures.

The Department of Health & Human Services has issued an advisory to help medical professionals better recognize the mental health symptoms that may come with long COVID.

The nine mental health symptoms highlighted in the advisory are fatigue; cognitive impairment, including brain fog; anxiety; depression; obsessive-compulsive disorder; sleep disorders; PTSD; psychotic disorder; and start of a substance use disorder.

The advisory noted that social factors can contribute to the mental health problems for racial and ethnic minorities; people with limited access to health care; people who already have behavioral health conditions and physical disabilities; and people who are lesbian, gay, bisexual, transgender, queer, or intersex.

“Long COVID has a range of burdensome physical symptoms and can take a toll on a person’s mental health. It can be very challenging for a person, whether they are impacted themselves, or they are a caregiver for someone who is affected,” Health and Human Services Secretary Xavier Becerra said in a statement. “This advisory helps to raise awareness, especially among primary care practitioners and clinicians who are often the ones treating patients with long COVID.”

The department says about 10% of people infected with COVID have at least one long COVID symptom. Physical symptoms include dizziness, stomach upset, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic coughing, chest pain, and abnormal movements. 

“We know that people living with long COVID need help today, and providers need help understanding what long COVID is and how to treat it,” Admiral Rachel Levine, MD, assistant secretary for health, said in the statement. “This advisory helps bridge that gap for the behavioral health impacts of long COVID.”

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

The Department of Health & Human Services has issued an advisory to help medical professionals better recognize the mental health symptoms that may come with long COVID.

The nine mental health symptoms highlighted in the advisory are fatigue; cognitive impairment, including brain fog; anxiety; depression; obsessive-compulsive disorder; sleep disorders; PTSD; psychotic disorder; and start of a substance use disorder.

The advisory noted that social factors can contribute to the mental health problems for racial and ethnic minorities; people with limited access to health care; people who already have behavioral health conditions and physical disabilities; and people who are lesbian, gay, bisexual, transgender, queer, or intersex.

“Long COVID has a range of burdensome physical symptoms and can take a toll on a person’s mental health. It can be very challenging for a person, whether they are impacted themselves, or they are a caregiver for someone who is affected,” Health and Human Services Secretary Xavier Becerra said in a statement. “This advisory helps to raise awareness, especially among primary care practitioners and clinicians who are often the ones treating patients with long COVID.”

The department says about 10% of people infected with COVID have at least one long COVID symptom. Physical symptoms include dizziness, stomach upset, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic coughing, chest pain, and abnormal movements. 

“We know that people living with long COVID need help today, and providers need help understanding what long COVID is and how to treat it,” Admiral Rachel Levine, MD, assistant secretary for health, said in the statement. “This advisory helps bridge that gap for the behavioral health impacts of long COVID.”

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

The Department of Health & Human Services has issued an advisory to help medical professionals better recognize the mental health symptoms that may come with long COVID.

The nine mental health symptoms highlighted in the advisory are fatigue; cognitive impairment, including brain fog; anxiety; depression; obsessive-compulsive disorder; sleep disorders; PTSD; psychotic disorder; and start of a substance use disorder.

The advisory noted that social factors can contribute to the mental health problems for racial and ethnic minorities; people with limited access to health care; people who already have behavioral health conditions and physical disabilities; and people who are lesbian, gay, bisexual, transgender, queer, or intersex.

“Long COVID has a range of burdensome physical symptoms and can take a toll on a person’s mental health. It can be very challenging for a person, whether they are impacted themselves, or they are a caregiver for someone who is affected,” Health and Human Services Secretary Xavier Becerra said in a statement. “This advisory helps to raise awareness, especially among primary care practitioners and clinicians who are often the ones treating patients with long COVID.”

The department says about 10% of people infected with COVID have at least one long COVID symptom. Physical symptoms include dizziness, stomach upset, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic coughing, chest pain, and abnormal movements. 

“We know that people living with long COVID need help today, and providers need help understanding what long COVID is and how to treat it,” Admiral Rachel Levine, MD, assistant secretary for health, said in the statement. “This advisory helps bridge that gap for the behavioral health impacts of long COVID.”

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

SAN DIEGO – The investigational once-weekly insulin icodec provided superior glucose control, compared with the once-daily basal insulins degludec and glargine in type 2 diabetes, results from two new phase 3a studies suggest.

Data from Novo Nordisk’s ONWARDS 1, comparing once-weekly icodec with once-daily glargine, and ONWARDS 3, comparing once-weekly icodec with daily degludec (Tresiba, Novo Nordisk), both in insulin-naive patients with type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association.

In both trials, primary endpoints of superiority and noninferiority in A1c reduction were achieved, and in ONWARDS 1, patients spent more time in target blood glucose range.

“I feel that weekly insulins have the potential to become transformational as preferred options for basal insulin replacement in people with type 2 diabetes in need of initiation of insulin therapy,” said Julio Rosenstock, MD, the lead author of ONWARDS 1.

Asked to comment, independent diabetes industry consultant Charles Alexander, MD, said: “The data certainly support approval of Icodec.”

Dr. Alexander said that an ideal candidate for once-weekly insulin “is someone who’s already on once-weekly [glucagon-like peptide-1 (GLP-1) agonist]. Then, taking your GLP-1 [agonist] and your basal insulin at the same time once a week makes a lot of sense ... Since they’re taking a weekly injection anyway, it’s relatively easy for a person to remember ‘When I take my weekly GLP-1 [agonist], I’ll take my weekly basal insulin.’ ”

However, he also pointed out: “Payers may say they don’t care about the convenience of once-weekly and they prefer to pay for the cheaper daily basal [insulin] ... I think a lot of people will continue to use [insulin] glargine because it is cheaper than either degludec or icodec.”

The data from ONWARDS 1 was published in the New England Journal of Medicine, and the data from ONWARDS 3 was published in JAMA.

Six ONWARDS trials make up Novo Nordisk’s phase 3a clinical development program comparing the efficacy and safety of once-weekly insulin icodec with once-daily basal insulin comparators.

Previously, findings from ONWARDS 2, in which patients with type 2 diabetes taking basal insulin had improved A1c after being switched to once-weekly icodec or once-daily degludec, were presented at the annual meeting of the European Association for the Study of Diabetes.    

Insulin icodec has been submitted for regulatory review in the United States, Canada, Europe, China, Australia, Switzerland, and Brazil, with decisions anticipated starting in the first half of 2024.
 

Hypoglycemia: Is the slight increase clinically significant?

One concern about the once-weekly insulins is that they might result in higher rates of hypoglycemia because they stay active in the body for so long.

Differences in rates of combined level 2 (clinically significant) and level 3 (severe) hypoglycemia were increased with borderline significance in ONWARDS 1.

In ONWARDS 3 there was a threefold significant difference, but the overall risk was still low, equating to one episode per patient per 3 years, said Ildiko Lingvay, MD, of University of Texas Southwestern Medical Center, Dallas, who is lead author for ONWARDS 1 and a co-author for ONWARDS 3.

Better glycemic control, with fewer injections

ONWARDS 1 was a 78-week, randomized, open-label, treat-to-target trial, with a main 52-week phase and a 26-week extension phase. A total of 984 patients with type 2 diabetes and A1c 7%-11% with no prior insulin treatment were randomized 1:1 to once-weekly icodec or daily insulin glargine. All baseline medications except sulfonylureas and glinides were continued.

The primary endpoint was change in A1c from baseline to week 52, and this dropped from 8.5% to 6.9% with icodec, versus 8.4% to 7.1% with glargine, a significant difference, confirming both noninferiority (P < .001) and superiority (P = .02) of icodec, Dr. Rosenstock said.

The percentage of time in blood glucose range (70-180 mg/dL) was also significantly higher with icodec than glargine (71.9% vs. 66.9%; P < .001), also confirming superiority.

Rates of combined clinically significant or severe hypoglycemia at 83 weeks were 0.30 versus 0.16 events per person-year of exposure at week 83 (P = .043). No new safety signals were identified, and incidences of adverse events were similar in the two groups.

A significantly higher proportion of participants achieved an A1c of less than 7% without clinically significant or severe hypoglycemia with once-weekly basal insulin icodec versus once-daily basal insulin glargine (52.6% vs. 42.6%).

ONWARDS 3 randomized 588 patients each to once-weekly insulin icodec plus once-weekly placebo or once-daily insulin degludec plus once-weekly placebo. The primary endpoint, change in A1c from baseline to week 26, fell from 8.6% to 7.0% with icodec and from 8.5% to 7.2% with degludec, confirming both noninferiority (P < .001) and superiority (P = .002).

There were no significant differences between the two insulins in change in fasting plasma glucose, mean weekly insulin dose, or body weight.

Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than in the degludec group from week 0 to 31 (0.31 vs. 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs. 0.12 events per patient-year exposure; P = .01).  

The percentage of patients achieving an A1c of less than 7% without level 2 or 3 hypoglycemia was 52.1% with icodec versus 39.9% with degludec.

Dr. Lingvay and Dr. Rosenstock have reported financial relationships with multiple companies.

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

SAN DIEGO – The investigational once-weekly insulin icodec provided superior glucose control, compared with the once-daily basal insulins degludec and glargine in type 2 diabetes, results from two new phase 3a studies suggest.

Data from Novo Nordisk’s ONWARDS 1, comparing once-weekly icodec with once-daily glargine, and ONWARDS 3, comparing once-weekly icodec with daily degludec (Tresiba, Novo Nordisk), both in insulin-naive patients with type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association.

In both trials, primary endpoints of superiority and noninferiority in A1c reduction were achieved, and in ONWARDS 1, patients spent more time in target blood glucose range.

“I feel that weekly insulins have the potential to become transformational as preferred options for basal insulin replacement in people with type 2 diabetes in need of initiation of insulin therapy,” said Julio Rosenstock, MD, the lead author of ONWARDS 1.

Asked to comment, independent diabetes industry consultant Charles Alexander, MD, said: “The data certainly support approval of Icodec.”

Dr. Alexander said that an ideal candidate for once-weekly insulin “is someone who’s already on once-weekly [glucagon-like peptide-1 (GLP-1) agonist]. Then, taking your GLP-1 [agonist] and your basal insulin at the same time once a week makes a lot of sense ... Since they’re taking a weekly injection anyway, it’s relatively easy for a person to remember ‘When I take my weekly GLP-1 [agonist], I’ll take my weekly basal insulin.’ ”

However, he also pointed out: “Payers may say they don’t care about the convenience of once-weekly and they prefer to pay for the cheaper daily basal [insulin] ... I think a lot of people will continue to use [insulin] glargine because it is cheaper than either degludec or icodec.”

The data from ONWARDS 1 was published in the New England Journal of Medicine, and the data from ONWARDS 3 was published in JAMA.

Six ONWARDS trials make up Novo Nordisk’s phase 3a clinical development program comparing the efficacy and safety of once-weekly insulin icodec with once-daily basal insulin comparators.

Previously, findings from ONWARDS 2, in which patients with type 2 diabetes taking basal insulin had improved A1c after being switched to once-weekly icodec or once-daily degludec, were presented at the annual meeting of the European Association for the Study of Diabetes.    

Insulin icodec has been submitted for regulatory review in the United States, Canada, Europe, China, Australia, Switzerland, and Brazil, with decisions anticipated starting in the first half of 2024.
 

Hypoglycemia: Is the slight increase clinically significant?

One concern about the once-weekly insulins is that they might result in higher rates of hypoglycemia because they stay active in the body for so long.

Differences in rates of combined level 2 (clinically significant) and level 3 (severe) hypoglycemia were increased with borderline significance in ONWARDS 1.

In ONWARDS 3 there was a threefold significant difference, but the overall risk was still low, equating to one episode per patient per 3 years, said Ildiko Lingvay, MD, of University of Texas Southwestern Medical Center, Dallas, who is lead author for ONWARDS 1 and a co-author for ONWARDS 3.

Better glycemic control, with fewer injections

ONWARDS 1 was a 78-week, randomized, open-label, treat-to-target trial, with a main 52-week phase and a 26-week extension phase. A total of 984 patients with type 2 diabetes and A1c 7%-11% with no prior insulin treatment were randomized 1:1 to once-weekly icodec or daily insulin glargine. All baseline medications except sulfonylureas and glinides were continued.

The primary endpoint was change in A1c from baseline to week 52, and this dropped from 8.5% to 6.9% with icodec, versus 8.4% to 7.1% with glargine, a significant difference, confirming both noninferiority (P < .001) and superiority (P = .02) of icodec, Dr. Rosenstock said.

The percentage of time in blood glucose range (70-180 mg/dL) was also significantly higher with icodec than glargine (71.9% vs. 66.9%; P < .001), also confirming superiority.

Rates of combined clinically significant or severe hypoglycemia at 83 weeks were 0.30 versus 0.16 events per person-year of exposure at week 83 (P = .043). No new safety signals were identified, and incidences of adverse events were similar in the two groups.

A significantly higher proportion of participants achieved an A1c of less than 7% without clinically significant or severe hypoglycemia with once-weekly basal insulin icodec versus once-daily basal insulin glargine (52.6% vs. 42.6%).

ONWARDS 3 randomized 588 patients each to once-weekly insulin icodec plus once-weekly placebo or once-daily insulin degludec plus once-weekly placebo. The primary endpoint, change in A1c from baseline to week 26, fell from 8.6% to 7.0% with icodec and from 8.5% to 7.2% with degludec, confirming both noninferiority (P < .001) and superiority (P = .002).

There were no significant differences between the two insulins in change in fasting plasma glucose, mean weekly insulin dose, or body weight.

Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than in the degludec group from week 0 to 31 (0.31 vs. 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs. 0.12 events per patient-year exposure; P = .01).  

The percentage of patients achieving an A1c of less than 7% without level 2 or 3 hypoglycemia was 52.1% with icodec versus 39.9% with degludec.

Dr. Lingvay and Dr. Rosenstock have reported financial relationships with multiple companies.

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

SAN DIEGO – The investigational once-weekly insulin icodec provided superior glucose control, compared with the once-daily basal insulins degludec and glargine in type 2 diabetes, results from two new phase 3a studies suggest.

Data from Novo Nordisk’s ONWARDS 1, comparing once-weekly icodec with once-daily glargine, and ONWARDS 3, comparing once-weekly icodec with daily degludec (Tresiba, Novo Nordisk), both in insulin-naive patients with type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association.

In both trials, primary endpoints of superiority and noninferiority in A1c reduction were achieved, and in ONWARDS 1, patients spent more time in target blood glucose range.

“I feel that weekly insulins have the potential to become transformational as preferred options for basal insulin replacement in people with type 2 diabetes in need of initiation of insulin therapy,” said Julio Rosenstock, MD, the lead author of ONWARDS 1.

Asked to comment, independent diabetes industry consultant Charles Alexander, MD, said: “The data certainly support approval of Icodec.”

Dr. Alexander said that an ideal candidate for once-weekly insulin “is someone who’s already on once-weekly [glucagon-like peptide-1 (GLP-1) agonist]. Then, taking your GLP-1 [agonist] and your basal insulin at the same time once a week makes a lot of sense ... Since they’re taking a weekly injection anyway, it’s relatively easy for a person to remember ‘When I take my weekly GLP-1 [agonist], I’ll take my weekly basal insulin.’ ”

However, he also pointed out: “Payers may say they don’t care about the convenience of once-weekly and they prefer to pay for the cheaper daily basal [insulin] ... I think a lot of people will continue to use [insulin] glargine because it is cheaper than either degludec or icodec.”

The data from ONWARDS 1 was published in the New England Journal of Medicine, and the data from ONWARDS 3 was published in JAMA.

Six ONWARDS trials make up Novo Nordisk’s phase 3a clinical development program comparing the efficacy and safety of once-weekly insulin icodec with once-daily basal insulin comparators.

Previously, findings from ONWARDS 2, in which patients with type 2 diabetes taking basal insulin had improved A1c after being switched to once-weekly icodec or once-daily degludec, were presented at the annual meeting of the European Association for the Study of Diabetes.    

Insulin icodec has been submitted for regulatory review in the United States, Canada, Europe, China, Australia, Switzerland, and Brazil, with decisions anticipated starting in the first half of 2024.
 

Hypoglycemia: Is the slight increase clinically significant?

One concern about the once-weekly insulins is that they might result in higher rates of hypoglycemia because they stay active in the body for so long.

Differences in rates of combined level 2 (clinically significant) and level 3 (severe) hypoglycemia were increased with borderline significance in ONWARDS 1.

In ONWARDS 3 there was a threefold significant difference, but the overall risk was still low, equating to one episode per patient per 3 years, said Ildiko Lingvay, MD, of University of Texas Southwestern Medical Center, Dallas, who is lead author for ONWARDS 1 and a co-author for ONWARDS 3.

Better glycemic control, with fewer injections

ONWARDS 1 was a 78-week, randomized, open-label, treat-to-target trial, with a main 52-week phase and a 26-week extension phase. A total of 984 patients with type 2 diabetes and A1c 7%-11% with no prior insulin treatment were randomized 1:1 to once-weekly icodec or daily insulin glargine. All baseline medications except sulfonylureas and glinides were continued.

The primary endpoint was change in A1c from baseline to week 52, and this dropped from 8.5% to 6.9% with icodec, versus 8.4% to 7.1% with glargine, a significant difference, confirming both noninferiority (P < .001) and superiority (P = .02) of icodec, Dr. Rosenstock said.

The percentage of time in blood glucose range (70-180 mg/dL) was also significantly higher with icodec than glargine (71.9% vs. 66.9%; P < .001), also confirming superiority.

Rates of combined clinically significant or severe hypoglycemia at 83 weeks were 0.30 versus 0.16 events per person-year of exposure at week 83 (P = .043). No new safety signals were identified, and incidences of adverse events were similar in the two groups.

A significantly higher proportion of participants achieved an A1c of less than 7% without clinically significant or severe hypoglycemia with once-weekly basal insulin icodec versus once-daily basal insulin glargine (52.6% vs. 42.6%).

ONWARDS 3 randomized 588 patients each to once-weekly insulin icodec plus once-weekly placebo or once-daily insulin degludec plus once-weekly placebo. The primary endpoint, change in A1c from baseline to week 26, fell from 8.6% to 7.0% with icodec and from 8.5% to 7.2% with degludec, confirming both noninferiority (P < .001) and superiority (P = .002).

There were no significant differences between the two insulins in change in fasting plasma glucose, mean weekly insulin dose, or body weight.

Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than in the degludec group from week 0 to 31 (0.31 vs. 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs. 0.12 events per patient-year exposure; P = .01).  

The percentage of patients achieving an A1c of less than 7% without level 2 or 3 hypoglycemia was 52.1% with icodec versus 39.9% with degludec.

Dr. Lingvay and Dr. Rosenstock have reported financial relationships with multiple companies.

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

SAN DIEGO – The American Diabetes Association now advises universal screening of people with type 2 diabetes and prediabetes for fatty liver disease and provides new recommendations for management in those with the condition or who are at risk for it.

Liver disease affects up to 70% of people with type 2 diabetes and is common in people with prediabetes and in those with type 1 diabetes who also have obesity. Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease in people with diabetes. It can lead to cirrhosis and liver cancer and is associated with an increased risk for cardiovascular disease and death. The condition includes non-alcoholic steatohepatitis (NASH).

“The ADA has recognized that this has become a big problem for their patients because NASH is becoming the number one cause of cirrhosis in people with type 2 diabetes and the number one cause of liver transplantation in the United States, so we have to do something about it,” Kenneth Cusi, MD, who presented a summary of the new guidance at the annual scientific sessions of the American Diabetes Association, said in an interview. 

The new ADA guidance was published as a mid-year update to the ADA’s Standards of Care in Diabetes–2023 in the section on “Comprehensive Medical Evaluation and Assessment of Comorbidities.”

Asked to comment, Atlanta endocrinologist Scott Isaacs, MD, said, “It is wonderful to see that the ADA has recognized NAFLD ... as the hepatic complication of type 2 diabetes and has updated the Standards of Care reflecting the current knowledge and evidence of this ubiquitous and often silent disease.”

The new ADA guidance aligns with those of other professional societies, including the American Association for the Study of Liver Diseases, the American Gastroenterological Society, and the American Association of Clinical Endocrinology.

Dr. Isaacs, who chaired the AACE guidance writing panel, noted, “The ADA update essentially repeats the same guidance in the AACE and AASLD documents. It is excellent to see this type of alignment of guidance among the major organizations.”
 

FIB-4: Easy calculation in the EHR

The ADA now advises screening all adults with type 2 diabetes or prediabetes, particularly those with obesity or cardiometabolic risk factors or established cardiovascular disease – even those with normal liver enzyme levels. People with type 1 diabetes who have obesity and/or cardiovascular risk factors are also to be screened for NAFLD.

The recommended screening tool is the fibrosis-4 index (FIB-4), a calculation that includes the patient’s age, liver enzyme levels, and platelet counts. A score of 1.3 or higher is considered high risk for clinically significant fibrosis and above 2.6 is very high-risk.

Dr. Cusi noted, “The reason we advise using the FIB-4 ... instead of liver enzymes as ADA advised in the past, is that now we know that 70% of people with type 2 diabetes have steatosis already and about one in five have fibrosis, but if you go by liver enzymes you will miss most of them. Liver enzymes are ineffective as a screening tool.”

The FIB-4 is “a simple tool we already have in our electronic health records (EHR) but we’re just simply not using it,” noted Dr. Cusi, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville. 

Indeed, Dr. Isaacs said, “The FIB-4 is a simple ... great screening test because it is essentially free.” But he cautioned that it has some limitations.

“It is a good test for ruling out advanced liver disease but can have false positives and false negatives. The FIB-4 cutoffs need to be adjusted for persons over 65 years old and [should] not to be used for persons under 30 years old.”

Dr. Isaacs also pointed out that, while the calculation can be done from a website, “even this adds time to a clinician’s busy day. Ideally, the FIB-4 should be automatically calculated in the EHR or on the lab report, similar to the [estimated glomerular filtration rate] calculation [for kidney function] and flagged if greater than 1.3.”

The ADA update also provides guidance on follow-up for patients flagged with the FIB-4, including when referral to a gastroenterologist or hepatologist is appropriate.
 

Treatment: Lifestyle modification plus GLP-1 agonists or pioglitazone

Lifestyle modification is recommended for all adults with diabetes or prediabetes and NAFLD, particularly those with overweight or obesity.  

In addition, the ADA now advises consideration of a using a glucagonlike peptide–1 (GLP-1) agonist with demonstrated benefits in NAFLD as adjunctive therapy to lifestyle interventions for weight loss in those with type 2 diabetes, particularly with overweight/obesity.

And for those with biopsy-proven NASH or who are identified with clinically significant liver fibrosis using non-invasive tests, either a GLP-1 agonist or pioglitazone are the “preferred treatments.”

However, insulin is the preferred treatment for hyperglycemia in adults with type 2 diabetes who have decompensated cirrhosis.

Dr. Isaacs commented, “Pioglitazone has so many benefits and a few known risks ... it is an underused medication. It is very inexpensive. Pioglitazone should be considered as a first line treatment for patients with type 2 diabetes and NAFLD.”

The ADA update also advises statin therapy for people with type 2 diabetes and NAFLD, given their increased cardiovascular risk. However, statins are not recommended for people with decompensated cirrhosis because of limited safety and efficacy data.

Dr. Cusi noted that he has been advocating for fatty liver screening in people with type 2 diabetes for over a decade.

“Doctors have already been adopting it, but ADA as an organization in diabetes care has a big impact. I dreamed many years ago that the day would come when we would screen all people with type 2 diabetes, and that day is today.”

Dr. Cusi is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, BMS, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, Thera Technologies, and MSD. Dr. Isaacs reports no relevant financial relationships.

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

SAN DIEGO – The American Diabetes Association now advises universal screening of people with type 2 diabetes and prediabetes for fatty liver disease and provides new recommendations for management in those with the condition or who are at risk for it.

Liver disease affects up to 70% of people with type 2 diabetes and is common in people with prediabetes and in those with type 1 diabetes who also have obesity. Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease in people with diabetes. It can lead to cirrhosis and liver cancer and is associated with an increased risk for cardiovascular disease and death. The condition includes non-alcoholic steatohepatitis (NASH).

“The ADA has recognized that this has become a big problem for their patients because NASH is becoming the number one cause of cirrhosis in people with type 2 diabetes and the number one cause of liver transplantation in the United States, so we have to do something about it,” Kenneth Cusi, MD, who presented a summary of the new guidance at the annual scientific sessions of the American Diabetes Association, said in an interview. 

The new ADA guidance was published as a mid-year update to the ADA’s Standards of Care in Diabetes–2023 in the section on “Comprehensive Medical Evaluation and Assessment of Comorbidities.”

Asked to comment, Atlanta endocrinologist Scott Isaacs, MD, said, “It is wonderful to see that the ADA has recognized NAFLD ... as the hepatic complication of type 2 diabetes and has updated the Standards of Care reflecting the current knowledge and evidence of this ubiquitous and often silent disease.”

The new ADA guidance aligns with those of other professional societies, including the American Association for the Study of Liver Diseases, the American Gastroenterological Society, and the American Association of Clinical Endocrinology.

Dr. Isaacs, who chaired the AACE guidance writing panel, noted, “The ADA update essentially repeats the same guidance in the AACE and AASLD documents. It is excellent to see this type of alignment of guidance among the major organizations.”
 

FIB-4: Easy calculation in the EHR

The ADA now advises screening all adults with type 2 diabetes or prediabetes, particularly those with obesity or cardiometabolic risk factors or established cardiovascular disease – even those with normal liver enzyme levels. People with type 1 diabetes who have obesity and/or cardiovascular risk factors are also to be screened for NAFLD.

The recommended screening tool is the fibrosis-4 index (FIB-4), a calculation that includes the patient’s age, liver enzyme levels, and platelet counts. A score of 1.3 or higher is considered high risk for clinically significant fibrosis and above 2.6 is very high-risk.

Dr. Cusi noted, “The reason we advise using the FIB-4 ... instead of liver enzymes as ADA advised in the past, is that now we know that 70% of people with type 2 diabetes have steatosis already and about one in five have fibrosis, but if you go by liver enzymes you will miss most of them. Liver enzymes are ineffective as a screening tool.”

The FIB-4 is “a simple tool we already have in our electronic health records (EHR) but we’re just simply not using it,” noted Dr. Cusi, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville. 

Indeed, Dr. Isaacs said, “The FIB-4 is a simple ... great screening test because it is essentially free.” But he cautioned that it has some limitations.

“It is a good test for ruling out advanced liver disease but can have false positives and false negatives. The FIB-4 cutoffs need to be adjusted for persons over 65 years old and [should] not to be used for persons under 30 years old.”

Dr. Isaacs also pointed out that, while the calculation can be done from a website, “even this adds time to a clinician’s busy day. Ideally, the FIB-4 should be automatically calculated in the EHR or on the lab report, similar to the [estimated glomerular filtration rate] calculation [for kidney function] and flagged if greater than 1.3.”

The ADA update also provides guidance on follow-up for patients flagged with the FIB-4, including when referral to a gastroenterologist or hepatologist is appropriate.
 

Treatment: Lifestyle modification plus GLP-1 agonists or pioglitazone

Lifestyle modification is recommended for all adults with diabetes or prediabetes and NAFLD, particularly those with overweight or obesity.  

In addition, the ADA now advises consideration of a using a glucagonlike peptide–1 (GLP-1) agonist with demonstrated benefits in NAFLD as adjunctive therapy to lifestyle interventions for weight loss in those with type 2 diabetes, particularly with overweight/obesity.

And for those with biopsy-proven NASH or who are identified with clinically significant liver fibrosis using non-invasive tests, either a GLP-1 agonist or pioglitazone are the “preferred treatments.”

However, insulin is the preferred treatment for hyperglycemia in adults with type 2 diabetes who have decompensated cirrhosis.

Dr. Isaacs commented, “Pioglitazone has so many benefits and a few known risks ... it is an underused medication. It is very inexpensive. Pioglitazone should be considered as a first line treatment for patients with type 2 diabetes and NAFLD.”

The ADA update also advises statin therapy for people with type 2 diabetes and NAFLD, given their increased cardiovascular risk. However, statins are not recommended for people with decompensated cirrhosis because of limited safety and efficacy data.

Dr. Cusi noted that he has been advocating for fatty liver screening in people with type 2 diabetes for over a decade.

“Doctors have already been adopting it, but ADA as an organization in diabetes care has a big impact. I dreamed many years ago that the day would come when we would screen all people with type 2 diabetes, and that day is today.”

Dr. Cusi is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, BMS, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, Thera Technologies, and MSD. Dr. Isaacs reports no relevant financial relationships.

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

SAN DIEGO – The American Diabetes Association now advises universal screening of people with type 2 diabetes and prediabetes for fatty liver disease and provides new recommendations for management in those with the condition or who are at risk for it.

Liver disease affects up to 70% of people with type 2 diabetes and is common in people with prediabetes and in those with type 1 diabetes who also have obesity. Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease in people with diabetes. It can lead to cirrhosis and liver cancer and is associated with an increased risk for cardiovascular disease and death. The condition includes non-alcoholic steatohepatitis (NASH).

“The ADA has recognized that this has become a big problem for their patients because NASH is becoming the number one cause of cirrhosis in people with type 2 diabetes and the number one cause of liver transplantation in the United States, so we have to do something about it,” Kenneth Cusi, MD, who presented a summary of the new guidance at the annual scientific sessions of the American Diabetes Association, said in an interview. 

The new ADA guidance was published as a mid-year update to the ADA’s Standards of Care in Diabetes–2023 in the section on “Comprehensive Medical Evaluation and Assessment of Comorbidities.”

Asked to comment, Atlanta endocrinologist Scott Isaacs, MD, said, “It is wonderful to see that the ADA has recognized NAFLD ... as the hepatic complication of type 2 diabetes and has updated the Standards of Care reflecting the current knowledge and evidence of this ubiquitous and often silent disease.”

The new ADA guidance aligns with those of other professional societies, including the American Association for the Study of Liver Diseases, the American Gastroenterological Society, and the American Association of Clinical Endocrinology.

Dr. Isaacs, who chaired the AACE guidance writing panel, noted, “The ADA update essentially repeats the same guidance in the AACE and AASLD documents. It is excellent to see this type of alignment of guidance among the major organizations.”
 

FIB-4: Easy calculation in the EHR

The ADA now advises screening all adults with type 2 diabetes or prediabetes, particularly those with obesity or cardiometabolic risk factors or established cardiovascular disease – even those with normal liver enzyme levels. People with type 1 diabetes who have obesity and/or cardiovascular risk factors are also to be screened for NAFLD.

The recommended screening tool is the fibrosis-4 index (FIB-4), a calculation that includes the patient’s age, liver enzyme levels, and platelet counts. A score of 1.3 or higher is considered high risk for clinically significant fibrosis and above 2.6 is very high-risk.

Dr. Cusi noted, “The reason we advise using the FIB-4 ... instead of liver enzymes as ADA advised in the past, is that now we know that 70% of people with type 2 diabetes have steatosis already and about one in five have fibrosis, but if you go by liver enzymes you will miss most of them. Liver enzymes are ineffective as a screening tool.”

The FIB-4 is “a simple tool we already have in our electronic health records (EHR) but we’re just simply not using it,” noted Dr. Cusi, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville. 

Indeed, Dr. Isaacs said, “The FIB-4 is a simple ... great screening test because it is essentially free.” But he cautioned that it has some limitations.

“It is a good test for ruling out advanced liver disease but can have false positives and false negatives. The FIB-4 cutoffs need to be adjusted for persons over 65 years old and [should] not to be used for persons under 30 years old.”

Dr. Isaacs also pointed out that, while the calculation can be done from a website, “even this adds time to a clinician’s busy day. Ideally, the FIB-4 should be automatically calculated in the EHR or on the lab report, similar to the [estimated glomerular filtration rate] calculation [for kidney function] and flagged if greater than 1.3.”

The ADA update also provides guidance on follow-up for patients flagged with the FIB-4, including when referral to a gastroenterologist or hepatologist is appropriate.
 

Treatment: Lifestyle modification plus GLP-1 agonists or pioglitazone

Lifestyle modification is recommended for all adults with diabetes or prediabetes and NAFLD, particularly those with overweight or obesity.  

In addition, the ADA now advises consideration of a using a glucagonlike peptide–1 (GLP-1) agonist with demonstrated benefits in NAFLD as adjunctive therapy to lifestyle interventions for weight loss in those with type 2 diabetes, particularly with overweight/obesity.

And for those with biopsy-proven NASH or who are identified with clinically significant liver fibrosis using non-invasive tests, either a GLP-1 agonist or pioglitazone are the “preferred treatments.”

However, insulin is the preferred treatment for hyperglycemia in adults with type 2 diabetes who have decompensated cirrhosis.

Dr. Isaacs commented, “Pioglitazone has so many benefits and a few known risks ... it is an underused medication. It is very inexpensive. Pioglitazone should be considered as a first line treatment for patients with type 2 diabetes and NAFLD.”

The ADA update also advises statin therapy for people with type 2 diabetes and NAFLD, given their increased cardiovascular risk. However, statins are not recommended for people with decompensated cirrhosis because of limited safety and efficacy data.

Dr. Cusi noted that he has been advocating for fatty liver screening in people with type 2 diabetes for over a decade.

“Doctors have already been adopting it, but ADA as an organization in diabetes care has a big impact. I dreamed many years ago that the day would come when we would screen all people with type 2 diabetes, and that day is today.”

Dr. Cusi is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, BMS, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, Thera Technologies, and MSD. Dr. Isaacs reports no relevant financial relationships.

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