MDedge Endocrinology

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of bupropion/naltrexone to glucagon-like peptide 1 (GLP-1) receptor agonists leads to a further 4%-5% total body weight loss (TBWL) in patients with obesity, including those who show a poor response to initial GLP-1 monotherapy.

METHODOLOGY:

• Some patients with obesity experience suboptimal weight loss with GLP-1 monotherapy; however, adding treatments targeting multiple pathways may offer synergistic effects and improve outcomes.
• Researchers retrospectively evaluated adult patients with body mass index (BMI) ≥ 30 who attended an obesity clinic in Vancouver, Canada, and received a GLP-1 receptor agonist (liraglutide or semaglutide) for at least 6 months.
• They compared patients who continued receiving GLP-1 monotherapy with those who received add-on bupropion/naltrexone (combination therapy).
• The percent TBWL was compared between the groups from the initiation of the GLP-1 or the addition of bupropion/naltrexone over a period of 6 and 12 months.
• Patients prescribed combination therapy were stratified into responders (≥ 5% TBWL) and nonresponders (< 5% TBWL) based on their initial response to GLP-1 monotherapy.

TAKEAWAY:

• Researchers included 415 patients with BMI ≥ 30 (mean age, 47.3 years; 75.6% women), of whom 320 continued receiving GLP-1 monotherapy and 95 received add-on bupropion/naltrexone (combination therapy); the mean follow-up period was 510.9 days.
• At 12 months, there was no significant difference in the percent TBWL among patients receiving the GLP-1 monotherapy or combination therapy (9.6% TBWL in both).
• However, when patients were stratified by their initial GLP-1 response, combination therapy led to a greater percent TBWL than monotherapy in both responders (P = .002) and nonresponders (P < .0001).
• After the addition of bupropion/naltrexone, the mean percent TBWL was 4.3% (P < .001) and 5.3% (P = .009) at 6 and 12 months, respectively, among the responders, and 3.7% (P = .009) and 4.0% (P = .02) at 6 and 12 months, respectively, among the nonresponders.

IN PRACTICE:

“Specific characteristics of individuals who benefit from the bupropion/naltrexone augmentation should be examined to identify patient populations wherein this may be of greatest benefit,” the authors wrote.

SOURCE:

This study, led by James Naude, Faculty of Medicine, University of British Columbia, Vancouver, Canada, was published in the International Journal of Obesity.

LIMITATIONS:

Virtual care and self-reported weights by patients owing to the COVID-19 pandemic could have introduced bias. Some of the data on weight and medication adherence were missing. Moreover, there was no placebo control; hence, there may be confounding by indication.

DISCLOSURES:

The study was not supported by any specific funding. Two of the authors reported receiving educational grants and speaker fees, with one currently being an advisory board member to various pharma companies and the other an advisory board member to a pharma company in the past.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of bupropion/naltrexone to glucagon-like peptide 1 (GLP-1) receptor agonists leads to a further 4%-5% total body weight loss (TBWL) in patients with obesity, including those who show a poor response to initial GLP-1 monotherapy.

METHODOLOGY:

• Some patients with obesity experience suboptimal weight loss with GLP-1 monotherapy; however, adding treatments targeting multiple pathways may offer synergistic effects and improve outcomes.
• Researchers retrospectively evaluated adult patients with body mass index (BMI) ≥ 30 who attended an obesity clinic in Vancouver, Canada, and received a GLP-1 receptor agonist (liraglutide or semaglutide) for at least 6 months.
• They compared patients who continued receiving GLP-1 monotherapy with those who received add-on bupropion/naltrexone (combination therapy).
• The percent TBWL was compared between the groups from the initiation of the GLP-1 or the addition of bupropion/naltrexone over a period of 6 and 12 months.
• Patients prescribed combination therapy were stratified into responders (≥ 5% TBWL) and nonresponders (< 5% TBWL) based on their initial response to GLP-1 monotherapy.

TAKEAWAY:

• Researchers included 415 patients with BMI ≥ 30 (mean age, 47.3 years; 75.6% women), of whom 320 continued receiving GLP-1 monotherapy and 95 received add-on bupropion/naltrexone (combination therapy); the mean follow-up period was 510.9 days.
• At 12 months, there was no significant difference in the percent TBWL among patients receiving the GLP-1 monotherapy or combination therapy (9.6% TBWL in both).
• However, when patients were stratified by their initial GLP-1 response, combination therapy led to a greater percent TBWL than monotherapy in both responders (P = .002) and nonresponders (P < .0001).
• After the addition of bupropion/naltrexone, the mean percent TBWL was 4.3% (P < .001) and 5.3% (P = .009) at 6 and 12 months, respectively, among the responders, and 3.7% (P = .009) and 4.0% (P = .02) at 6 and 12 months, respectively, among the nonresponders.

IN PRACTICE:

“Specific characteristics of individuals who benefit from the bupropion/naltrexone augmentation should be examined to identify patient populations wherein this may be of greatest benefit,” the authors wrote.

SOURCE:

This study, led by James Naude, Faculty of Medicine, University of British Columbia, Vancouver, Canada, was published in the International Journal of Obesity.

LIMITATIONS:

Virtual care and self-reported weights by patients owing to the COVID-19 pandemic could have introduced bias. Some of the data on weight and medication adherence were missing. Moreover, there was no placebo control; hence, there may be confounding by indication.

DISCLOSURES:

The study was not supported by any specific funding. Two of the authors reported receiving educational grants and speaker fees, with one currently being an advisory board member to various pharma companies and the other an advisory board member to a pharma company in the past.

A version of this article appeared on Medscape.com.

TOPLINE:

The addition of bupropion/naltrexone to glucagon-like peptide 1 (GLP-1) receptor agonists leads to a further 4%-5% total body weight loss (TBWL) in patients with obesity, including those who show a poor response to initial GLP-1 monotherapy.

METHODOLOGY:

• Some patients with obesity experience suboptimal weight loss with GLP-1 monotherapy; however, adding treatments targeting multiple pathways may offer synergistic effects and improve outcomes.
• Researchers retrospectively evaluated adult patients with body mass index (BMI) ≥ 30 who attended an obesity clinic in Vancouver, Canada, and received a GLP-1 receptor agonist (liraglutide or semaglutide) for at least 6 months.
• They compared patients who continued receiving GLP-1 monotherapy with those who received add-on bupropion/naltrexone (combination therapy).
• The percent TBWL was compared between the groups from the initiation of the GLP-1 or the addition of bupropion/naltrexone over a period of 6 and 12 months.
• Patients prescribed combination therapy were stratified into responders (≥ 5% TBWL) and nonresponders (< 5% TBWL) based on their initial response to GLP-1 monotherapy.

TAKEAWAY:

• Researchers included 415 patients with BMI ≥ 30 (mean age, 47.3 years; 75.6% women), of whom 320 continued receiving GLP-1 monotherapy and 95 received add-on bupropion/naltrexone (combination therapy); the mean follow-up period was 510.9 days.
• At 12 months, there was no significant difference in the percent TBWL among patients receiving the GLP-1 monotherapy or combination therapy (9.6% TBWL in both).
• However, when patients were stratified by their initial GLP-1 response, combination therapy led to a greater percent TBWL than monotherapy in both responders (P = .002) and nonresponders (P < .0001).
• After the addition of bupropion/naltrexone, the mean percent TBWL was 4.3% (P < .001) and 5.3% (P = .009) at 6 and 12 months, respectively, among the responders, and 3.7% (P = .009) and 4.0% (P = .02) at 6 and 12 months, respectively, among the nonresponders.

IN PRACTICE:

“Specific characteristics of individuals who benefit from the bupropion/naltrexone augmentation should be examined to identify patient populations wherein this may be of greatest benefit,” the authors wrote.

SOURCE:

This study, led by James Naude, Faculty of Medicine, University of British Columbia, Vancouver, Canada, was published in the International Journal of Obesity.

LIMITATIONS:

Virtual care and self-reported weights by patients owing to the COVID-19 pandemic could have introduced bias. Some of the data on weight and medication adherence were missing. Moreover, there was no placebo control; hence, there may be confounding by indication.

DISCLOSURES:

The study was not supported by any specific funding. Two of the authors reported receiving educational grants and speaker fees, with one currently being an advisory board member to various pharma companies and the other an advisory board member to a pharma company in the past.

A version of this article appeared on Medscape.com.

TOPLINE:

In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).

METHODOLOGY:

• Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
• This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
• Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
• GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
• CGM-derived glycemic patterns were compared between the participants with and without GDM.

TAKEAWAY:

• Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
• Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
• The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
• Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.

IN PRACTICE:

“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”

SOURCE:

The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.

LIMITATIONS:

To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.

DISCLOSURES:

The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.

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

TOPLINE:

In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).

METHODOLOGY:

• Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
• This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
• Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
• GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
• CGM-derived glycemic patterns were compared between the participants with and without GDM.

TAKEAWAY:

• Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
• Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
• The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
• Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.

IN PRACTICE:

“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”

SOURCE:

The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.

LIMITATIONS:

To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.

DISCLOSURES:

The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.

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

TOPLINE:

In women with gestational diabetes (GD), continuous glucose monitoring (CGM) shows elevated glycemic metrics earlier in pregnancy compared with the standard oral glucose tolerance test (OGTT).

METHODOLOGY:

• Earlier diagnosis and treatment of GDM may mitigate some perinatal risks, but the traditional OGTT at 24-28 weeks’ gestation delivers inconsistent results in early pregnancy, potentially leading to missed cases or overdiagnosis.
• This prospective noninterventional observational study conducted at two US academic-based clinical sites from June 2020 to December 2021 assessed CGM-derived glycemic patterns in 768 participants (mean age, 33 years; 77% White) enrolled prior to 17 weeks’ gestation with singleton pregnancy and an initial A1c level < 6.5%.
• Participants were encouraged to wear a blinded Dexcom G6 Pro CGM System sensor continuously until the day of delivery, with a median CGM wear duration of 67 days prior to OGTT.
• GDM was diagnosed using an OGTT conducted between 24 and 34 weeks’ gestation, which sorted women into those with GDM (n = 58) or without GDM (n = 710).
• CGM-derived glycemic patterns were compared between the participants with and without GDM.

TAKEAWAY:

• Women with GDM had a higher mean glucose (109 ± 13 vs 100 ± 8 mg/dL; P < .001) and greater glucose SD (23 ± 4 vs 19 ± 3; P < .001) than those without GDM throughout the gestational period prior to OGTT.
• Women with GDM spent lesser time in glycemic ranges of 63-140 mg/dL (87% ± 11% vs 94% ± 4%; P < .001) and 63-120 mg/dL (70% ± 17% vs 84% ± 8%; P < .001) throughout gestation than those without GDM prior to OGTT.
• The daytime and overnight mean glucose levels were higher in those with vs without GDM and attributed to increased hyperglycemia rather than decreased hypoglycemia, with those with GDM spending more time > 120 mg/dL and > 140 mg/dL and less time < 63 mg/dL and < 54 mg/dL.
• Mean glucose and percent time in the > 120 mg/dL and > 140 mg/dL ranges were higher in those with GDM as early as 13-14 weeks of gestation, which persisted at each 2-week period prior to OGTT.

IN PRACTICE:

“CGM could be used in addition to or instead of OGTT to screen individuals at risk for hyperglycemia during pregnancy, even as early as the first trimester,” the authors wrote, adding that “CGM could potentially play a pivotal role in providing timely identification of distinct glycemic patterns indicative of early dysglycemia.”

SOURCE:

The study, led by Celeste Durnwald, MD, Maternal-Fetal Medicine Research Program, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, was published online in Diabetes Care.

LIMITATIONS:

To include participants with possible early GDM, the study allowed the inclusion of up to 14 days of CGM data after OGTT in the overall gestational period and up to 10 days in the first and second trimesters. A detailed analysis of glycemia at the earliest timepoint of pregnancy could not be conducted as the first trimester data were limited. The findings may not be generalizable to a population with gestational hyperglycemia, as only 58 participants were identified with GDM using OGTT.

DISCLOSURES:

The study was supported by the Leona M. and Harry B. Helmsley Charitable Trust and UnitedHealth Group. Some authors reported performing advisory work, receiving research support and consultancy fees, and being on scientific advisory boards through their employer, while several authors reported that their institution received funds on their behalf from various pharmaceutical, healthcare, and medical device companies.

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

NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.

As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.

Several drugs in various stages of development are aimed at preserving or building muscle mass and boosting fat loss when used in combination with one of these medications for weight loss. Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.

One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.

Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.

Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.

Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.

“Wouldn’t it be nice if there was a drug that built up muscle mass?”

Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.

The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”

Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”

The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”

And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”

“We have to also focus on ‘first, do no harm’”

Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”

Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.

“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”

“Wherever the GLP-1s go, we go”

In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”

Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
 

A version of this article appeared on Medscape.com.

NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.

As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.

Several drugs in various stages of development are aimed at preserving or building muscle mass and boosting fat loss when used in combination with one of these medications for weight loss. Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.

One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.

Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.

Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.

Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.

“Wouldn’t it be nice if there was a drug that built up muscle mass?”

Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.

The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”

Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”

The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”

And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”

“We have to also focus on ‘first, do no harm’”

Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”

Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.

“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”

“Wherever the GLP-1s go, we go”

In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”

Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
 

A version of this article appeared on Medscape.com.

NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.

As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.

Several drugs in various stages of development are aimed at preserving or building muscle mass and boosting fat loss when used in combination with one of these medications for weight loss. Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.

One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.

Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.

Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.

Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.

“Wouldn’t it be nice if there was a drug that built up muscle mass?”

Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.

The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”

Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”

The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”

And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”

“We have to also focus on ‘first, do no harm’”

Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”

Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.

“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”

“Wherever the GLP-1s go, we go”

In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”

Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
 

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.

The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers. 

Is obesity the new smoking? Not exactly.

Tracing a direct line between excess fat and cancer is much less clear-cut than it is with tobacco. While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.

Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?

There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?

When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.

A Consistent but Complicated Relationship

Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.

Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.

“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.

In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.

That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.

At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes. 

It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.

Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.

One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells. 

But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.

That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.

How Big Is the Effect?

While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably. 

Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.

With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.

A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).

Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.

Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.

CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.

Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.

When Do Extra Pounds Matter?

When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?

Some evidence suggests there’s no “safe” time for putting on excess pounds.

A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years. 

The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.

Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers. 

An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.

There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.

But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.

“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”

Does Weight Loss Help?

With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.

Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.

Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers. 

A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.

But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.

Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”

“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”

Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations. 

People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week. 

“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.

A version of this article appeared on Medscape.com.

TOPLINE:

An early serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) has been validated as a safe and useful screening test with 100% specificity for predicting recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients on tapering regimes from long‐term chronic glucocorticoid therapy (CGT).

METHODOLOGY:

• A retrospective review of 250-µg Synacthen test (SST) results performed in patients on tapering CGT doses from a single-center rheumatology department over 12 months.
• A total of 60 SSTs were performed in 58 patients, all in the morning (7-12 AM) after withholding CGT for 48 hours.
• Peripheral blood was sampled for cortisol at baseline, 30 minutes, and 60 minutes.
• Adrenal insufficiency (AI) was defined as a peak serum cortisol concentration.

TAKEAWAY:

• The mean duration of CGT (all prednisolone) was 63 months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%), with a mean daily dose of 3.4 mg at the time of SST.
• With the investigators’ previously reported basal serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided.
• A basal serum cortisol concentration of > 227 nmol/L had a specificity of 100% for predicting passing the SST, while a basal serum cortisol concentration of ≤ 55 nmol/L had a 100% sensitivity for predicting failure.
• A mean daily prednisolone dosing at the time of SST in patients with AI was significantly higher than that with normal SSTs (5.7 vs 2.9 mg, respectively; P = .01).

IN PRACTICE:

“This offers a more rapid, convenient, and cost‐effective screening method for patients requiring biochemical assessment of the HPA axis with the potential for significant resource savings without any adverse impact on patient safety,” the authors wrote.

SOURCE:

The study was conducted by Ella Sharma, of the Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and colleagues and published online on May 19, 2024, as a letter in Clinical Endocrinology.

LIMITATIONS:

Not provided.

DISCLOSURES: 

Not provided.
 

A version of this article appeared on Medscape.com.

TOPLINE:

An early serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) has been validated as a safe and useful screening test with 100% specificity for predicting recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients on tapering regimes from long‐term chronic glucocorticoid therapy (CGT).

METHODOLOGY:

• A retrospective review of 250-µg Synacthen test (SST) results performed in patients on tapering CGT doses from a single-center rheumatology department over 12 months.
• A total of 60 SSTs were performed in 58 patients, all in the morning (7-12 AM) after withholding CGT for 48 hours.
• Peripheral blood was sampled for cortisol at baseline, 30 minutes, and 60 minutes.
• Adrenal insufficiency (AI) was defined as a peak serum cortisol concentration.

TAKEAWAY:

• The mean duration of CGT (all prednisolone) was 63 months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%), with a mean daily dose of 3.4 mg at the time of SST.
• With the investigators’ previously reported basal serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided.
• A basal serum cortisol concentration of > 227 nmol/L had a specificity of 100% for predicting passing the SST, while a basal serum cortisol concentration of ≤ 55 nmol/L had a 100% sensitivity for predicting failure.
• A mean daily prednisolone dosing at the time of SST in patients with AI was significantly higher than that with normal SSTs (5.7 vs 2.9 mg, respectively; P = .01).

IN PRACTICE:

“This offers a more rapid, convenient, and cost‐effective screening method for patients requiring biochemical assessment of the HPA axis with the potential for significant resource savings without any adverse impact on patient safety,” the authors wrote.

SOURCE:

The study was conducted by Ella Sharma, of the Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and colleagues and published online on May 19, 2024, as a letter in Clinical Endocrinology.

LIMITATIONS:

Not provided.

DISCLOSURES: 

Not provided.
 

A version of this article appeared on Medscape.com.

TOPLINE:

An early serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) has been validated as a safe and useful screening test with 100% specificity for predicting recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients on tapering regimes from long‐term chronic glucocorticoid therapy (CGT).

METHODOLOGY:

• A retrospective review of 250-µg Synacthen test (SST) results performed in patients on tapering CGT doses from a single-center rheumatology department over 12 months.
• A total of 60 SSTs were performed in 58 patients, all in the morning (7-12 AM) after withholding CGT for 48 hours.
• Peripheral blood was sampled for cortisol at baseline, 30 minutes, and 60 minutes.
• Adrenal insufficiency (AI) was defined as a peak serum cortisol concentration.

TAKEAWAY:

• The mean duration of CGT (all prednisolone) was 63 months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%), with a mean daily dose of 3.4 mg at the time of SST.
• With the investigators’ previously reported basal serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided.
• A basal serum cortisol concentration of > 227 nmol/L had a specificity of 100% for predicting passing the SST, while a basal serum cortisol concentration of ≤ 55 nmol/L had a 100% sensitivity for predicting failure.
• A mean daily prednisolone dosing at the time of SST in patients with AI was significantly higher than that with normal SSTs (5.7 vs 2.9 mg, respectively; P = .01).

IN PRACTICE:

“This offers a more rapid, convenient, and cost‐effective screening method for patients requiring biochemical assessment of the HPA axis with the potential for significant resource savings without any adverse impact on patient safety,” the authors wrote.

SOURCE:

The study was conducted by Ella Sharma, of the Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and colleagues and published online on May 19, 2024, as a letter in Clinical Endocrinology.

LIMITATIONS:

Not provided.

DISCLOSURES: 

Not provided.
 

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) has drawn interest in ophthalmology for its potential to track disease trends in huge populations, such as the 38.4 million people in the United States with diabetes who are at risk for diabetic eye disease. However, a recent study using AI to detect diabetic retinopathy from retinal photo screenings has found wide disparities in the quality of data being fed into the algorithm.

And screening photos captured in nine primary care settings were three times more likely to be unusable than those obtained in two ophthalmology clinics, a study at Temple University in Philadelphia found. The results of the new research were reported at the Association for Research in Vision and Ophthalmology (ARVO) 2024 annual meeting.

“AI-assisted diabetic retinopathy screenings were more successful when completed in the ophthalmology clinic setting compared to the primary care setting,” study leader Madelyn Class, a medical student at Temple, told this news organization. One key difference, Ms. Class said, was that the specialty clinics used a photographer training in capturing ophthalmic images, while the primary care sites had medical assistants taking the photos.
 

Challenges of Screening in Primary Care

The American Diabetes Association acknowledged in a 2017 position statement that retinal photography has the potential to bring screening into settings where optometrists or ophthalmologists are unavailable. This study showed the potential may not yet be realized.

In the primary care setting, 42.5% of retinal photos were ungradable compared with 14.5% in the specialty settings.

The number of patients diagnosed with more-than-mild diabetic retinopathy also varied significantly between the two settings — 13% in primary care and 24% in ophthalmology — as did the rates of follow-up appointments: 58% and 80%, respectively.

“It seems user error played a role in the quality of photographs that were taken,” Ms. Class said. “Some of the images we received from the primary care settings were actually of the eyelid, or even the curtains on the wall, rather than the fundus.

“All the camera operators in the study received training on the imaging device,” Ms. Class added. “This suggests that some of the photographers were rushed, out of practice, or simply no longer interested in taking photos,” she said. “Apparently, we will have to continuously monitor the performance of each photographer to ensure that quality photos are being taken.”

The findings may also point to the need for using different equipment for screening in primary care, Ms. Class added. “Robotic as opposed to manual cameras may help eliminate some of the user error that was experienced with primary care screenings,” she said.

Need for Training ‘Fixable’

These findings demonstrate the challenges of capturing usable retinal images outside of an eye care professional’s office, according to Jennifer Lim, MD, director of the retina service at the University of Illinois Chicago.

“This study illustrates that implementation is the rub of AI,” Dr. Lim told this news organization. “Getting primary care doctors and clinics to want to adopt and figure out how to implement AI screening [for diabetic retinopathy] in a healthcare system is difficult, so I applaud the Temple University system for trying to integrate retinal photography-based AI screening into the primary care outpatient centers and comparing outcomes to the ophthalmology clinics.”

The study showed that photographers need not only initial training but also monitoring to avoid ungradable images, Dr. Lim added, a problem that is “fixable.”

“It’s going to take a lot of work to get the message out to the primary care practices that these autonomous, cloud-based systems are available and effective for detecting retinopathy,” she said.

But the effort is worth it, she added: “It doesn’t take much time to take these photos for diabetic retinopathy screening, and the potential benefits are huge because the earlier you diagnose diabetic retinopathy that’s more than mild, the more likely the patient can be sent for eye care in a timely fashion and thus prevent visual loss from diabetic retinopathy.”

Ms. Class had no relevant disclosures. Dr. Lim disclosed a past relationship with Eyenuk, the maker of retinal screening cameras.

A version of this article appeared on Medscape.com .

Artificial intelligence (AI) has drawn interest in ophthalmology for its potential to track disease trends in huge populations, such as the 38.4 million people in the United States with diabetes who are at risk for diabetic eye disease. However, a recent study using AI to detect diabetic retinopathy from retinal photo screenings has found wide disparities in the quality of data being fed into the algorithm.

And screening photos captured in nine primary care settings were three times more likely to be unusable than those obtained in two ophthalmology clinics, a study at Temple University in Philadelphia found. The results of the new research were reported at the Association for Research in Vision and Ophthalmology (ARVO) 2024 annual meeting.

“AI-assisted diabetic retinopathy screenings were more successful when completed in the ophthalmology clinic setting compared to the primary care setting,” study leader Madelyn Class, a medical student at Temple, told this news organization. One key difference, Ms. Class said, was that the specialty clinics used a photographer training in capturing ophthalmic images, while the primary care sites had medical assistants taking the photos.
 

Challenges of Screening in Primary Care

The American Diabetes Association acknowledged in a 2017 position statement that retinal photography has the potential to bring screening into settings where optometrists or ophthalmologists are unavailable. This study showed the potential may not yet be realized.

In the primary care setting, 42.5% of retinal photos were ungradable compared with 14.5% in the specialty settings.

The number of patients diagnosed with more-than-mild diabetic retinopathy also varied significantly between the two settings — 13% in primary care and 24% in ophthalmology — as did the rates of follow-up appointments: 58% and 80%, respectively.

“It seems user error played a role in the quality of photographs that were taken,” Ms. Class said. “Some of the images we received from the primary care settings were actually of the eyelid, or even the curtains on the wall, rather than the fundus.

“All the camera operators in the study received training on the imaging device,” Ms. Class added. “This suggests that some of the photographers were rushed, out of practice, or simply no longer interested in taking photos,” she said. “Apparently, we will have to continuously monitor the performance of each photographer to ensure that quality photos are being taken.”

The findings may also point to the need for using different equipment for screening in primary care, Ms. Class added. “Robotic as opposed to manual cameras may help eliminate some of the user error that was experienced with primary care screenings,” she said.

Need for Training ‘Fixable’

These findings demonstrate the challenges of capturing usable retinal images outside of an eye care professional’s office, according to Jennifer Lim, MD, director of the retina service at the University of Illinois Chicago.

“This study illustrates that implementation is the rub of AI,” Dr. Lim told this news organization. “Getting primary care doctors and clinics to want to adopt and figure out how to implement AI screening [for diabetic retinopathy] in a healthcare system is difficult, so I applaud the Temple University system for trying to integrate retinal photography-based AI screening into the primary care outpatient centers and comparing outcomes to the ophthalmology clinics.”

The study showed that photographers need not only initial training but also monitoring to avoid ungradable images, Dr. Lim added, a problem that is “fixable.”

“It’s going to take a lot of work to get the message out to the primary care practices that these autonomous, cloud-based systems are available and effective for detecting retinopathy,” she said.

But the effort is worth it, she added: “It doesn’t take much time to take these photos for diabetic retinopathy screening, and the potential benefits are huge because the earlier you diagnose diabetic retinopathy that’s more than mild, the more likely the patient can be sent for eye care in a timely fashion and thus prevent visual loss from diabetic retinopathy.”

Ms. Class had no relevant disclosures. Dr. Lim disclosed a past relationship with Eyenuk, the maker of retinal screening cameras.

A version of this article appeared on Medscape.com .

Artificial intelligence (AI) has drawn interest in ophthalmology for its potential to track disease trends in huge populations, such as the 38.4 million people in the United States with diabetes who are at risk for diabetic eye disease. However, a recent study using AI to detect diabetic retinopathy from retinal photo screenings has found wide disparities in the quality of data being fed into the algorithm.

And screening photos captured in nine primary care settings were three times more likely to be unusable than those obtained in two ophthalmology clinics, a study at Temple University in Philadelphia found. The results of the new research were reported at the Association for Research in Vision and Ophthalmology (ARVO) 2024 annual meeting.

“AI-assisted diabetic retinopathy screenings were more successful when completed in the ophthalmology clinic setting compared to the primary care setting,” study leader Madelyn Class, a medical student at Temple, told this news organization. One key difference, Ms. Class said, was that the specialty clinics used a photographer training in capturing ophthalmic images, while the primary care sites had medical assistants taking the photos.
 

Challenges of Screening in Primary Care

The American Diabetes Association acknowledged in a 2017 position statement that retinal photography has the potential to bring screening into settings where optometrists or ophthalmologists are unavailable. This study showed the potential may not yet be realized.

In the primary care setting, 42.5% of retinal photos were ungradable compared with 14.5% in the specialty settings.

The number of patients diagnosed with more-than-mild diabetic retinopathy also varied significantly between the two settings — 13% in primary care and 24% in ophthalmology — as did the rates of follow-up appointments: 58% and 80%, respectively.

“It seems user error played a role in the quality of photographs that were taken,” Ms. Class said. “Some of the images we received from the primary care settings were actually of the eyelid, or even the curtains on the wall, rather than the fundus.

“All the camera operators in the study received training on the imaging device,” Ms. Class added. “This suggests that some of the photographers were rushed, out of practice, or simply no longer interested in taking photos,” she said. “Apparently, we will have to continuously monitor the performance of each photographer to ensure that quality photos are being taken.”

The findings may also point to the need for using different equipment for screening in primary care, Ms. Class added. “Robotic as opposed to manual cameras may help eliminate some of the user error that was experienced with primary care screenings,” she said.

Need for Training ‘Fixable’

These findings demonstrate the challenges of capturing usable retinal images outside of an eye care professional’s office, according to Jennifer Lim, MD, director of the retina service at the University of Illinois Chicago.

“This study illustrates that implementation is the rub of AI,” Dr. Lim told this news organization. “Getting primary care doctors and clinics to want to adopt and figure out how to implement AI screening [for diabetic retinopathy] in a healthcare system is difficult, so I applaud the Temple University system for trying to integrate retinal photography-based AI screening into the primary care outpatient centers and comparing outcomes to the ophthalmology clinics.”

The study showed that photographers need not only initial training but also monitoring to avoid ungradable images, Dr. Lim added, a problem that is “fixable.”

“It’s going to take a lot of work to get the message out to the primary care practices that these autonomous, cloud-based systems are available and effective for detecting retinopathy,” she said.

But the effort is worth it, she added: “It doesn’t take much time to take these photos for diabetic retinopathy screening, and the potential benefits are huge because the earlier you diagnose diabetic retinopathy that’s more than mild, the more likely the patient can be sent for eye care in a timely fashion and thus prevent visual loss from diabetic retinopathy.”

Ms. Class had no relevant disclosures. Dr. Lim disclosed a past relationship with Eyenuk, the maker of retinal screening cameras.

A version of this article appeared on Medscape.com .

WASHINGTON — In contrast with a previous study that found glucagon-like peptide 1 (GLP-1) receptor agonists associated with an increased risk for acute pancreatitis and bowel obstruction, a new retrospective study found no significant link to these complications. The new data did, however, reinforce an association between GLP-1s and gastroparesis and biliary disease, specifically gallstones.

One of the big differences from the previous study, published in JAMA in October 2023 by Sodhi and colleagues , is that the current research was able to account for initial body mass index (BMI), said Benjamin Liu, MD, a resident in internal medicine at Case Western Reserve University School of Medicine, Cleveland, Ohio.

This is important, he explained in his presentation (abstract 1074) at the annual Digestive Disease Week^® 2024, because obesity on its own is associated with an increased risk for some of these gastrointestinal (GI) outcomes.

“They did an excellent study,” Dr. Liu said. “But their platform did not allow them to match participants for BMI.”

Another distinction between the two studies is that the JAMA study excluded people who had diabetes 90 days before or 30 days following the start of GLP-1 therapy.

Instead, Dr. Liu said, he and colleague Gengqing Song, MD, “just made it simple” and excluded anyone with diabetes or an A1c ≥ 6.5.

We didn’t want participants with diabetes because “we were looking at GLP-1s for weight loss,” Dr. Liu explained.

Although some clinical trials have already assessed adverse events of these medications, “clinical trials are not always a perfect representation of the real world,” Dr. Liu said in an interview. “So, it’s important to do real-world studies to see just what actually goes on.”
 

Reassessing GI Complications 

In the current study, the researchers identified 105,793 patients from the TriNetX healthcare database taking a GLP-1, either semaglutide or liraglutide, for weight loss and 8794 patients taking 8 mg naltrexone/90 mg bupropion. After propensity matching, including for BMI, there were 8792 patients in each group.

They were identified in the database between 2011 and 2023. Researchers noted their first-ever occurrence of acute pancreatitis, bowel obstruction, gastroparesis, or biliary disease during the study period.

Participants had a BMI ≥ 30 kg/m². In addition to BMI, propensity score matching included demographics, alcohol use, smoking, hyperlipidemia, and abdominal surgery. A second analysis specifically did not match participants for BMI.

The researchers found no significant association between GLP-1s and acute pancreatitis (adjusted hazard ratio [HR], 1.19; 95% CI, 0.66-2.14).

The labeling for semaglutide and liraglutide warns about an increased risk for acute pancreatitis, “but real-world studies and clinical trials are increasingly suggesting there is no increased risk,” Dr. Liu said.

They also did not find a significant association between GLP-1s and bowel obstruction (HR, 1.30; 95% CI, 0.69-2.18).

Despite the current findings, more research — especially prospective data — is needed to confirm pancreatitis as well as other GI risks like bowel obstruction potentially associated with GLP-1s, he added.

The study did, however, find an elevated risk for biliary disease (HR, 1.27; 95% CI, 1.02-1.59) in the BMI-matched cohorts.

This could be due to the rapidity of weight loss, Dr. Liu suggested. “We found that semaglutide caused more weight loss at 6 and 12 months than naltrexone/bupropion, and it did so at a faster rate. That falls in line with other data that suggest if you lose weight too fast, you actually have an increased risk of gallstones,” he said.

Rapid weight loss can release cholesterol into the body, which then collects in the bile ducts and causes gallstones. This risk for gallstone formation with rapid weight loss is also seen after bariatric surgery, Dr. Liu said.

Without BMI matching, he noted, the increased risk for biliary disease was no longer significant (HR, 1.21; 95% CI, 0.96-1.52).

The researchers also reported a significant association between GLP-1s and gastroparesis (HR, 2.30; 95% CI, 1.19-4.46), confirming the results of the JAMA study “but at a much lower incidence rate once we excluded all patients with diabetes,” said Dr. Liu. The JAMA study had a HR of 3.67 for gastroparesis (95% CI, 1.15-11.90).
 

Weighing in on the Results

“Overall, their study design looks sound,” said Mahyar Etminan, PharmD, associate professor of medicine at the University of British Columbia in Vancouver and an author of the JAMA study. He agreed that Dr. Liu’s research confirmed their findings about gastroparesis and biliary disease.

However, “I interpret the results with intestinal obstruction and pancreatitis as more inconclusive than no risk,” he added.

Session co-moderator and gastroenterologist and motility specialist with Stanford Health Care in California, Linda Anh Bui Nguyen, MD, AGAF, said that she thinks “it’s a promising study.

“But with any retrospective study where you’re looking at ICD-10 [International Classification of Diseases, Tenth Revision] codes, it really depends on the coders. The code could be subjective and could be wrong,” said Dr. Nguyen, clinical professor of medicine at Stanford Medical School, California.

For example, the diagnosis of gastroparesis requires a normal endoscopy and a gastric emptying test. “But we find that, frequently, patients are being given a diagnosis of gastroparesis without the test,” she said.

An unanswered question also remains regarding how pancreatitis or biliary disease is being diagnosed: “Was it imaging, lab testing, or symptoms?” she said in an interview. “For example, if patients had pain on the right side, did they call it biliary?”

Dr. Nguyen added that it is difficult to get this kind of detail in retrospective studies. She also agreed with Dr. Liu that prospective studies are warranted.

The study was independently supported. Dr. Liu, Dr. Etminan, and Dr. Nguyen had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — In contrast with a previous study that found glucagon-like peptide 1 (GLP-1) receptor agonists associated with an increased risk for acute pancreatitis and bowel obstruction, a new retrospective study found no significant link to these complications. The new data did, however, reinforce an association between GLP-1s and gastroparesis and biliary disease, specifically gallstones.

One of the big differences from the previous study, published in JAMA in October 2023 by Sodhi and colleagues , is that the current research was able to account for initial body mass index (BMI), said Benjamin Liu, MD, a resident in internal medicine at Case Western Reserve University School of Medicine, Cleveland, Ohio.

This is important, he explained in his presentation (abstract 1074) at the annual Digestive Disease Week^® 2024, because obesity on its own is associated with an increased risk for some of these gastrointestinal (GI) outcomes.

“They did an excellent study,” Dr. Liu said. “But their platform did not allow them to match participants for BMI.”

Another distinction between the two studies is that the JAMA study excluded people who had diabetes 90 days before or 30 days following the start of GLP-1 therapy.

Instead, Dr. Liu said, he and colleague Gengqing Song, MD, “just made it simple” and excluded anyone with diabetes or an A1c ≥ 6.5.

We didn’t want participants with diabetes because “we were looking at GLP-1s for weight loss,” Dr. Liu explained.

Although some clinical trials have already assessed adverse events of these medications, “clinical trials are not always a perfect representation of the real world,” Dr. Liu said in an interview. “So, it’s important to do real-world studies to see just what actually goes on.”
 

Reassessing GI Complications 

In the current study, the researchers identified 105,793 patients from the TriNetX healthcare database taking a GLP-1, either semaglutide or liraglutide, for weight loss and 8794 patients taking 8 mg naltrexone/90 mg bupropion. After propensity matching, including for BMI, there were 8792 patients in each group.

They were identified in the database between 2011 and 2023. Researchers noted their first-ever occurrence of acute pancreatitis, bowel obstruction, gastroparesis, or biliary disease during the study period.

Participants had a BMI ≥ 30 kg/m². In addition to BMI, propensity score matching included demographics, alcohol use, smoking, hyperlipidemia, and abdominal surgery. A second analysis specifically did not match participants for BMI.

The researchers found no significant association between GLP-1s and acute pancreatitis (adjusted hazard ratio [HR], 1.19; 95% CI, 0.66-2.14).

The labeling for semaglutide and liraglutide warns about an increased risk for acute pancreatitis, “but real-world studies and clinical trials are increasingly suggesting there is no increased risk,” Dr. Liu said.

They also did not find a significant association between GLP-1s and bowel obstruction (HR, 1.30; 95% CI, 0.69-2.18).

Despite the current findings, more research — especially prospective data — is needed to confirm pancreatitis as well as other GI risks like bowel obstruction potentially associated with GLP-1s, he added.

The study did, however, find an elevated risk for biliary disease (HR, 1.27; 95% CI, 1.02-1.59) in the BMI-matched cohorts.

This could be due to the rapidity of weight loss, Dr. Liu suggested. “We found that semaglutide caused more weight loss at 6 and 12 months than naltrexone/bupropion, and it did so at a faster rate. That falls in line with other data that suggest if you lose weight too fast, you actually have an increased risk of gallstones,” he said.

Rapid weight loss can release cholesterol into the body, which then collects in the bile ducts and causes gallstones. This risk for gallstone formation with rapid weight loss is also seen after bariatric surgery, Dr. Liu said.

Without BMI matching, he noted, the increased risk for biliary disease was no longer significant (HR, 1.21; 95% CI, 0.96-1.52).

The researchers also reported a significant association between GLP-1s and gastroparesis (HR, 2.30; 95% CI, 1.19-4.46), confirming the results of the JAMA study “but at a much lower incidence rate once we excluded all patients with diabetes,” said Dr. Liu. The JAMA study had a HR of 3.67 for gastroparesis (95% CI, 1.15-11.90).
 

Weighing in on the Results

“Overall, their study design looks sound,” said Mahyar Etminan, PharmD, associate professor of medicine at the University of British Columbia in Vancouver and an author of the JAMA study. He agreed that Dr. Liu’s research confirmed their findings about gastroparesis and biliary disease.

However, “I interpret the results with intestinal obstruction and pancreatitis as more inconclusive than no risk,” he added.

Session co-moderator and gastroenterologist and motility specialist with Stanford Health Care in California, Linda Anh Bui Nguyen, MD, AGAF, said that she thinks “it’s a promising study.

“But with any retrospective study where you’re looking at ICD-10 [International Classification of Diseases, Tenth Revision] codes, it really depends on the coders. The code could be subjective and could be wrong,” said Dr. Nguyen, clinical professor of medicine at Stanford Medical School, California.

For example, the diagnosis of gastroparesis requires a normal endoscopy and a gastric emptying test. “But we find that, frequently, patients are being given a diagnosis of gastroparesis without the test,” she said.

An unanswered question also remains regarding how pancreatitis or biliary disease is being diagnosed: “Was it imaging, lab testing, or symptoms?” she said in an interview. “For example, if patients had pain on the right side, did they call it biliary?”

Dr. Nguyen added that it is difficult to get this kind of detail in retrospective studies. She also agreed with Dr. Liu that prospective studies are warranted.

The study was independently supported. Dr. Liu, Dr. Etminan, and Dr. Nguyen had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

WASHINGTON — In contrast with a previous study that found glucagon-like peptide 1 (GLP-1) receptor agonists associated with an increased risk for acute pancreatitis and bowel obstruction, a new retrospective study found no significant link to these complications. The new data did, however, reinforce an association between GLP-1s and gastroparesis and biliary disease, specifically gallstones.

One of the big differences from the previous study, published in JAMA in October 2023 by Sodhi and colleagues , is that the current research was able to account for initial body mass index (BMI), said Benjamin Liu, MD, a resident in internal medicine at Case Western Reserve University School of Medicine, Cleveland, Ohio.

This is important, he explained in his presentation (abstract 1074) at the annual Digestive Disease Week^® 2024, because obesity on its own is associated with an increased risk for some of these gastrointestinal (GI) outcomes.

“They did an excellent study,” Dr. Liu said. “But their platform did not allow them to match participants for BMI.”

Another distinction between the two studies is that the JAMA study excluded people who had diabetes 90 days before or 30 days following the start of GLP-1 therapy.

Instead, Dr. Liu said, he and colleague Gengqing Song, MD, “just made it simple” and excluded anyone with diabetes or an A1c ≥ 6.5.

We didn’t want participants with diabetes because “we were looking at GLP-1s for weight loss,” Dr. Liu explained.

Although some clinical trials have already assessed adverse events of these medications, “clinical trials are not always a perfect representation of the real world,” Dr. Liu said in an interview. “So, it’s important to do real-world studies to see just what actually goes on.”
 

Reassessing GI Complications 

In the current study, the researchers identified 105,793 patients from the TriNetX healthcare database taking a GLP-1, either semaglutide or liraglutide, for weight loss and 8794 patients taking 8 mg naltrexone/90 mg bupropion. After propensity matching, including for BMI, there were 8792 patients in each group.

They were identified in the database between 2011 and 2023. Researchers noted their first-ever occurrence of acute pancreatitis, bowel obstruction, gastroparesis, or biliary disease during the study period.

Participants had a BMI ≥ 30 kg/m². In addition to BMI, propensity score matching included demographics, alcohol use, smoking, hyperlipidemia, and abdominal surgery. A second analysis specifically did not match participants for BMI.

The researchers found no significant association between GLP-1s and acute pancreatitis (adjusted hazard ratio [HR], 1.19; 95% CI, 0.66-2.14).

The labeling for semaglutide and liraglutide warns about an increased risk for acute pancreatitis, “but real-world studies and clinical trials are increasingly suggesting there is no increased risk,” Dr. Liu said.

They also did not find a significant association between GLP-1s and bowel obstruction (HR, 1.30; 95% CI, 0.69-2.18).

Despite the current findings, more research — especially prospective data — is needed to confirm pancreatitis as well as other GI risks like bowel obstruction potentially associated with GLP-1s, he added.

The study did, however, find an elevated risk for biliary disease (HR, 1.27; 95% CI, 1.02-1.59) in the BMI-matched cohorts.

This could be due to the rapidity of weight loss, Dr. Liu suggested. “We found that semaglutide caused more weight loss at 6 and 12 months than naltrexone/bupropion, and it did so at a faster rate. That falls in line with other data that suggest if you lose weight too fast, you actually have an increased risk of gallstones,” he said.

Rapid weight loss can release cholesterol into the body, which then collects in the bile ducts and causes gallstones. This risk for gallstone formation with rapid weight loss is also seen after bariatric surgery, Dr. Liu said.

Without BMI matching, he noted, the increased risk for biliary disease was no longer significant (HR, 1.21; 95% CI, 0.96-1.52).

The researchers also reported a significant association between GLP-1s and gastroparesis (HR, 2.30; 95% CI, 1.19-4.46), confirming the results of the JAMA study “but at a much lower incidence rate once we excluded all patients with diabetes,” said Dr. Liu. The JAMA study had a HR of 3.67 for gastroparesis (95% CI, 1.15-11.90).
 

Weighing in on the Results

“Overall, their study design looks sound,” said Mahyar Etminan, PharmD, associate professor of medicine at the University of British Columbia in Vancouver and an author of the JAMA study. He agreed that Dr. Liu’s research confirmed their findings about gastroparesis and biliary disease.

However, “I interpret the results with intestinal obstruction and pancreatitis as more inconclusive than no risk,” he added.

Session co-moderator and gastroenterologist and motility specialist with Stanford Health Care in California, Linda Anh Bui Nguyen, MD, AGAF, said that she thinks “it’s a promising study.

“But with any retrospective study where you’re looking at ICD-10 [International Classification of Diseases, Tenth Revision] codes, it really depends on the coders. The code could be subjective and could be wrong,” said Dr. Nguyen, clinical professor of medicine at Stanford Medical School, California.

For example, the diagnosis of gastroparesis requires a normal endoscopy and a gastric emptying test. “But we find that, frequently, patients are being given a diagnosis of gastroparesis without the test,” she said.

An unanswered question also remains regarding how pancreatitis or biliary disease is being diagnosed: “Was it imaging, lab testing, or symptoms?” she said in an interview. “For example, if patients had pain on the right side, did they call it biliary?”

Dr. Nguyen added that it is difficult to get this kind of detail in retrospective studies. She also agreed with Dr. Liu that prospective studies are warranted.

The study was independently supported. Dr. Liu, Dr. Etminan, and Dr. Nguyen had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

Each month I set out on an expedition to find a topic for this column. I came across a new book Rebel Health by Susannah Fox that I thought might be a good one. It’s both a treatise on the shortcomings of healthcare and a Baedeker for patients on how to find their way to being better served. Her argument is that many patients’ needs are unmet and their conditions are often invisible to us in mainstream healthcare. We fail to find solutions to help them. Patients would benefit from more open access to their records and more resources to take control of their own health, she argues. A few chapters in, I thought, “Oh, here we go, another diatribe on doctors and how we care most about how to keep patients in their rightful, subordinate place.” The “Rebel” title is provocative and implies patients need to overthrow the status quo. Well, I am part of the establishment. I stopped reading. This book doesn’t apply to me, I thought.

After all, I’m a healthcare progressive, right? My notes and results have been open for years. I encourage shared decision-making and try to empower patients as much as treat them. The idea that I or my colleagues are unwilling to do whatever is necessary to meet our patients’ needs was maddening. We dedicate our lives to it. My young daughter often greets me in the morning by asking if I’ll be working tonight. Most nights, I am — answering patient messages, collaborating with colleagues to help patients, keeping up with medical knowledge. I was angry at what felt like unjust criticism, especially that we’d neglect patients because their problems are not obvious or worse, there is not enough money to be made helping them. Harrumph.

Kaiser Permanente

That’s when I realized the best thing for me was to read the entire book and digest the arguments. I pride myself on being well-read, but I fall into a common trap: the podcasts I listen to, news I consume, and books I read mostly affirm my beliefs. It is a healthy choice to seek dispositive data and contrasting stories rather than always feeding our personal opinions.

Rebel Health was not written by Robespierre. It was penned by a thoughtful, articulate patient advocate with over 20 years experience. She has far more bona fides than I could achieve in two lifetimes. In the book, she reminds us that scientific advances in the last 100 years have made medicine more effective but also disintermediated caregivers, family, and patients. Patients and caregivers can not only help but also offer innovative and customized solutions to their problems. She describes four patient archetypes: seekers, networkers, solvers, and champions, and offers a four-quadrant model to visualize how some patients are unhelped by our current healthcare system. She advocates for frictionless, open access to health data and tries to inspire patients to connect, innovate, and create to fill the voids that exist in healthcare. We have come a long way from the immured system of a decade ago; much of that is the result of patient advocates. But healthcare is still too costly, too fragmented and too many patients unhelped. “Community is a superpower,” she writes. I agree, we should assemble all the heroes in the universe for this challenge.

Fox also tells stories of patients who solved diagnostic dilemmas through their own research and advocacy. I thought of my own contrasting experiences of patients whose DIY care was based on misinformation and how their false confidence led to poorer outcomes for them. I want to share with her readers how physicians feel hurt when patients question our competence or place the opinion of an adversarial Redditor over ours. Physicians are sometimes wrong and often in doubt. Most of us care deeply about our patients regardless of how visible their diagnosis or how easy they are to appease.

We don’t have time to engage back-and-forth on an insignificantly abnormal test they find in their open chart or why B12 and hormone testing would not be helpful for their disease. It’s also not the patients’ fault. Having unfettered access to their data might add work, but it also adds value. They are trying to learn and be active in their care. Physicians are frustrated mostly because we don’t have time to meet these unmet needs. Everyone is trying their best and we all want the same thing: patients to be satisfied and well.

As for learning the skill of being open-minded, an excellent reference is Adam Grant’s Think Again. It’s inspiring and instructive of how we can all be more open, including how to have productive arguments rather than fruitless fights. We live in divisive times. Perhaps if we all put in effort to be open-minded, push down righteous indignation, and advance more honest humility we’d all be a bit better off.

Patients are the primary audience for the Rebel Health book. Yet, as we care about them and we all want to make healthcare better, it is worth reading in its entirety. I told my daughter I don’t have to work tonight because I’ve written my article this month. When she’s a little older, I’ll tell her all about it. To be successful, she’ll have to be as open-minded as she is smart. She can learn both.

I have no conflict of interest in the book.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Each month I set out on an expedition to find a topic for this column. I came across a new book Rebel Health by Susannah Fox that I thought might be a good one. It’s both a treatise on the shortcomings of healthcare and a Baedeker for patients on how to find their way to being better served. Her argument is that many patients’ needs are unmet and their conditions are often invisible to us in mainstream healthcare. We fail to find solutions to help them. Patients would benefit from more open access to their records and more resources to take control of their own health, she argues. A few chapters in, I thought, “Oh, here we go, another diatribe on doctors and how we care most about how to keep patients in their rightful, subordinate place.” The “Rebel” title is provocative and implies patients need to overthrow the status quo. Well, I am part of the establishment. I stopped reading. This book doesn’t apply to me, I thought.

After all, I’m a healthcare progressive, right? My notes and results have been open for years. I encourage shared decision-making and try to empower patients as much as treat them. The idea that I or my colleagues are unwilling to do whatever is necessary to meet our patients’ needs was maddening. We dedicate our lives to it. My young daughter often greets me in the morning by asking if I’ll be working tonight. Most nights, I am — answering patient messages, collaborating with colleagues to help patients, keeping up with medical knowledge. I was angry at what felt like unjust criticism, especially that we’d neglect patients because their problems are not obvious or worse, there is not enough money to be made helping them. Harrumph.

Kaiser Permanente

That’s when I realized the best thing for me was to read the entire book and digest the arguments. I pride myself on being well-read, but I fall into a common trap: the podcasts I listen to, news I consume, and books I read mostly affirm my beliefs. It is a healthy choice to seek dispositive data and contrasting stories rather than always feeding our personal opinions.

Rebel Health was not written by Robespierre. It was penned by a thoughtful, articulate patient advocate with over 20 years experience. She has far more bona fides than I could achieve in two lifetimes. In the book, she reminds us that scientific advances in the last 100 years have made medicine more effective but also disintermediated caregivers, family, and patients. Patients and caregivers can not only help but also offer innovative and customized solutions to their problems. She describes four patient archetypes: seekers, networkers, solvers, and champions, and offers a four-quadrant model to visualize how some patients are unhelped by our current healthcare system. She advocates for frictionless, open access to health data and tries to inspire patients to connect, innovate, and create to fill the voids that exist in healthcare. We have come a long way from the immured system of a decade ago; much of that is the result of patient advocates. But healthcare is still too costly, too fragmented and too many patients unhelped. “Community is a superpower,” she writes. I agree, we should assemble all the heroes in the universe for this challenge.

Fox also tells stories of patients who solved diagnostic dilemmas through their own research and advocacy. I thought of my own contrasting experiences of patients whose DIY care was based on misinformation and how their false confidence led to poorer outcomes for them. I want to share with her readers how physicians feel hurt when patients question our competence or place the opinion of an adversarial Redditor over ours. Physicians are sometimes wrong and often in doubt. Most of us care deeply about our patients regardless of how visible their diagnosis or how easy they are to appease.

We don’t have time to engage back-and-forth on an insignificantly abnormal test they find in their open chart or why B12 and hormone testing would not be helpful for their disease. It’s also not the patients’ fault. Having unfettered access to their data might add work, but it also adds value. They are trying to learn and be active in their care. Physicians are frustrated mostly because we don’t have time to meet these unmet needs. Everyone is trying their best and we all want the same thing: patients to be satisfied and well.

As for learning the skill of being open-minded, an excellent reference is Adam Grant’s Think Again. It’s inspiring and instructive of how we can all be more open, including how to have productive arguments rather than fruitless fights. We live in divisive times. Perhaps if we all put in effort to be open-minded, push down righteous indignation, and advance more honest humility we’d all be a bit better off.

Patients are the primary audience for the Rebel Health book. Yet, as we care about them and we all want to make healthcare better, it is worth reading in its entirety. I told my daughter I don’t have to work tonight because I’ve written my article this month. When she’s a little older, I’ll tell her all about it. To be successful, she’ll have to be as open-minded as she is smart. She can learn both.

I have no conflict of interest in the book.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Each month I set out on an expedition to find a topic for this column. I came across a new book Rebel Health by Susannah Fox that I thought might be a good one. It’s both a treatise on the shortcomings of healthcare and a Baedeker for patients on how to find their way to being better served. Her argument is that many patients’ needs are unmet and their conditions are often invisible to us in mainstream healthcare. We fail to find solutions to help them. Patients would benefit from more open access to their records and more resources to take control of their own health, she argues. A few chapters in, I thought, “Oh, here we go, another diatribe on doctors and how we care most about how to keep patients in their rightful, subordinate place.” The “Rebel” title is provocative and implies patients need to overthrow the status quo. Well, I am part of the establishment. I stopped reading. This book doesn’t apply to me, I thought.

After all, I’m a healthcare progressive, right? My notes and results have been open for years. I encourage shared decision-making and try to empower patients as much as treat them. The idea that I or my colleagues are unwilling to do whatever is necessary to meet our patients’ needs was maddening. We dedicate our lives to it. My young daughter often greets me in the morning by asking if I’ll be working tonight. Most nights, I am — answering patient messages, collaborating with colleagues to help patients, keeping up with medical knowledge. I was angry at what felt like unjust criticism, especially that we’d neglect patients because their problems are not obvious or worse, there is not enough money to be made helping them. Harrumph.

Kaiser Permanente

That’s when I realized the best thing for me was to read the entire book and digest the arguments. I pride myself on being well-read, but I fall into a common trap: the podcasts I listen to, news I consume, and books I read mostly affirm my beliefs. It is a healthy choice to seek dispositive data and contrasting stories rather than always feeding our personal opinions.

Rebel Health was not written by Robespierre. It was penned by a thoughtful, articulate patient advocate with over 20 years experience. She has far more bona fides than I could achieve in two lifetimes. In the book, she reminds us that scientific advances in the last 100 years have made medicine more effective but also disintermediated caregivers, family, and patients. Patients and caregivers can not only help but also offer innovative and customized solutions to their problems. She describes four patient archetypes: seekers, networkers, solvers, and champions, and offers a four-quadrant model to visualize how some patients are unhelped by our current healthcare system. She advocates for frictionless, open access to health data and tries to inspire patients to connect, innovate, and create to fill the voids that exist in healthcare. We have come a long way from the immured system of a decade ago; much of that is the result of patient advocates. But healthcare is still too costly, too fragmented and too many patients unhelped. “Community is a superpower,” she writes. I agree, we should assemble all the heroes in the universe for this challenge.

Fox also tells stories of patients who solved diagnostic dilemmas through their own research and advocacy. I thought of my own contrasting experiences of patients whose DIY care was based on misinformation and how their false confidence led to poorer outcomes for them. I want to share with her readers how physicians feel hurt when patients question our competence or place the opinion of an adversarial Redditor over ours. Physicians are sometimes wrong and often in doubt. Most of us care deeply about our patients regardless of how visible their diagnosis or how easy they are to appease.

We don’t have time to engage back-and-forth on an insignificantly abnormal test they find in their open chart or why B12 and hormone testing would not be helpful for their disease. It’s also not the patients’ fault. Having unfettered access to their data might add work, but it also adds value. They are trying to learn and be active in their care. Physicians are frustrated mostly because we don’t have time to meet these unmet needs. Everyone is trying their best and we all want the same thing: patients to be satisfied and well.

As for learning the skill of being open-minded, an excellent reference is Adam Grant’s Think Again. It’s inspiring and instructive of how we can all be more open, including how to have productive arguments rather than fruitless fights. We live in divisive times. Perhaps if we all put in effort to be open-minded, push down righteous indignation, and advance more honest humility we’d all be a bit better off.

Patients are the primary audience for the Rebel Health book. Yet, as we care about them and we all want to make healthcare better, it is worth reading in its entirety. I told my daughter I don’t have to work tonight because I’ve written my article this month. When she’s a little older, I’ll tell her all about it. To be successful, she’ll have to be as open-minded as she is smart. She can learn both.

I have no conflict of interest in the book.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].