Concerns have been raised about GLP-1 receptor agonists causing unintended weight loss in older adults. A new VA study has put that worry to rest, finding no significant difference in weight loss with semaglutide use among veterans 65 or older compared to those who are younger. The authors concluded that age does not appear to be a “robust predictor” of semaglutide’s effect on weight.
DALLAS — Diabetes guidelines recommend it. Doctors prescribe it. Weight loss centers bemoan it. Celebrities (mis)use it and pharmacists can’t keep it in stock. Semaglutide has upended diabetes treatment and weight management like no other drug.
Semaglutide is a glucagonlike peptide-1 (GLP-1) receptor agonist (RA) that reduces blood glucose levels by stimulating insulin secretion while suppressing glucagon secretion. It also increase uptake of glucose, boosts glycogen synthesis in peripheral tissues, promotes satiety and slows gastric emptying. The combination of effects has made it a powerful tool in management of Type 2 diabetes and weight loss. Semaglutide is available as a subcutaneous weekly injection or as a daily pill.
While social media influencers might be the best known users, veterans could be the poster image for the drug. A quarter of veterans have diabetes; 40% are classified as obese; and, given the relationship between obesity and diabetes, a significant percentage are both.
The VA has responded by covering semaglutide as the preferred GLP-1 RA for Type 2 diabetes. According to the VA Pharmacy Benefits Management Services, semaglutide can be prescribed to veterans with Type 2 diabetes (T2DM) who have inadequate glycemic control despite taking metformin and/or sulfonylurea and have a baseline HbA1c of at least 7.5%.
Semaglutide also can be prescribed to veterans for chronic weight management if they have a body mass index (BMI) above 30 kg/m2 or above 27 kg/m2 and at least one weight-related comorbidity such as hypertension, Type 2 diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis or nonalcoholic fatty liver disease. They also must have failed to lose at least 5% of body weight or be contraindicated for two other weight management medications or have other issues requiring additional support to lose weight.
Unintended Weight Loss
As veterans switched from another GLP-1 RA to semaglutide in response to its preferred status, clinicians at the VA North Texas Health Care System (VANTHCS) in Dallas sought to better understand the impact of the drug on elderly veterans, particularly in terms of unintended weight loss. In younger patients, losing weight while achieving better control of blood glucose is typically seen as a bonus. For elderly patients, it might not be as beneficial, given the association between weight loss and increased morbidity and mortality in this population.
Researchers at VANTHCS undertook a study to determine whether elderly veterans with T2D experienced greater weight loss than younger veterans and, consequently, whether interventions are required. “If the difference is significant, greater attention is needed in the elderly initiating semaglutide to prevent adverse outcomes,” the researchers noted.1
The team evaluated records for 1,045 veterans treated for Type 2 diabetes at the Dallas VAMC who were prescribed semaglutide for the first time between Oct. 1, 2020, and Oct. 25, 2021, and stayed on it for at least 3 months. Of those, only 177 had documented weights taken within 90 days prior to starting semaglutide and follow-up weights at 3 months, give or take 1 month, and did not have one of the exclusionary conditions.
The 177 veterans included 111 participants age 65 or older and 66 between the ages of 18 and 64. The older group had lower baseline A1c (8.2% vs. 8.9%), higher average age (72 vs. 56) and higher rate of heart failure (26.1% vs. 10.6%). The elderly veterans were 95.5% male and 51% white, while the younger cohort was 87.9% male and 42% white.
The demographics are fairly typical of the VA population, the researchers noted. “The overall veteran population in the United States of America is mostly comprised of non-Hispanic white, elderly male veterans,” they said. “The sample population reflects similar characteristics and supports the study’s relevance to the larger veteran population.”
The researchers found that, while the elderly veterans lost slightly less weight at 3 months and slightly more at 6 months as measured by both percentage of body weight shed and reduction in kilograms than younger veterans, the differences were not statistically significant. The presence of heart failure also did not affect the results of the study. The difference in weight loss between the two doses prescribed, 0.5 mg and 1 mg, also was negligible.
Adverse events that led to discontinuation or dose decrease occurred at a higher rate in the younger group. Two of the elderly veterans discontinued the medication because of nausea, vomiting, abdominal pain or decreased appetite, while three of those under age 65 discontinued for similar gastrointestinal (GI) reasons. One also experienced hypoglycemia. A fourth veteran in the younger group decreased the dose from 0.5 mg to 0.25 mg because of GI issues.
“Based on the results of this study, age is likely not a robust predictor of semaglutide’s influence on weight in veterans diagnosed with T2DM,” the VA team concluded. “Larger, higher-powered prospective studies designed to account for multiple confounders would be necessary to further explore this endpoint, especially with the recent approval of semaglutide 2 mg SC weekly for T2DM.”
- Huynh G, Runeberg H, Weideman R. Evaluating Weight Loss With Semaglutide in Elderly Patients With Type II Diabetes. J Pharm Technol. 2023 Feb;39(1):10-15. doi: 10.1177/87551225221137493. Epub 2022 Nov 30.
