What Factors Influence a Patient’s Success on GLP-1s?

Longer treatment duration, not having diabetes, and using semaglutide were among the factors associated with better weight reduction over 12 months among patients taking GLP-1 receptor agonists (RA), a cohort study suggested.

“Treatment responses differ among patients receiving GLP-1 RAs, and the weight fluctuations and associated factors following [their] use have not been adequately characterized,” Linong Ji, MD, of Peking University People’s Hospital in Beijing, China, told Medscape Medical News.

The findings, published online in Diabetes, Obesity and Metabolism, “may provide novel insights into weight fluctuations after GLP-1 RA treatment in a real-world setting,” he said, potentially advancing the development of individualized strategies for patients.

‘Corroborates Other Studies’

Researchers conducted a real-world, single-center, retrospective study of 679 patients with overweight or obesity who initiated GLP-1 RA treatment between November 2022 and October 2024.

At baseline, participants had a mean age of 37 years, and 31% were men. The mean BMI was 33.4, and 21% were diagnosed with diabetes.

The GLP-1 RAs used in the study included semaglutide (Ozempic), liraglutide (Victoza), lixisenatide (Lyxumia), beinaglutide (Yishengtai), exenatide (Bydureon), dulaglutide (Trulicity), and PEG-loxenatide (Fulaimei). All were available for participants with both type 2 diabetes (T2D) and overweight/obesity.

For participants with overweight/obesity but without T2D, only Ozempic or Victoza were routinely prescribed, with off-label documentation and informed consent.

Weight measurements were collected during in-person clinic visits, and weight fluctuation curves were stratified into three phenotypes — Successful Weight Reduction, Remaining Stable, and Weight Regain.

Subsequently, the association between potential influencing factors and weight fluctuations was estimated by univariate and multivariate logistic regression. Subgroup analyses were performed in participants with obesity, prediabetes, and in those using liraglutide or semaglutide.

Researchers found significant differences in the duration of GLP-1 RA treatment across groups at the 3-, 6-, and 12-month follow-ups. The Successful Weight Reduction group had a significantly longer duration of GLP-1 RA treatment than the Remaining Stable group and a longer duration at both the 6- and 12-month follow-ups than the Weight Regain group.

Diabetes status also showed group differences. At both the 3- and 6-month follow-ups, the proportion of patients with T2D in the Successful Weight Reduction group was lower than in the Remaining Stable group.

Types of GLP-1 RAs varied between groups, and at the 3- and 6-month follow-ups, the Successful Weight Reduction group was more likely to have initiated treatment with semaglutide than the Remaining Stable group.

Patients with a longer duration of GLP-1 RA treatment (odds ratio [OR], 1.014) and higher Homeostasis Model Assessment of Beta-Cell Function levels (OR, 4.912) were more likely to achieve successful weight reduction at the 12-month follow-up.

Nondiabetic status (OR, 2.176) and using semaglutide (OR, 2.138) were associated with successful weight reduction at the 6-month follow-up.

In addition, a higher percentage of body fat in both men (OR, 3.990) and women (OR, 2.266) was associated with successful weight reduction.

The weight regain group had a higher baseline estimated glomerular filtration rate than the Successful Weight Reduction group and the Remaining Stable group at 3-month follow-up, especially among participants with prediabetes. Ji said this finding surprised him. Patients with obesity often exhibit a state of renal hyperfiltration, characterized by elevated renal plasma flow and glomerular filtration rate, which can be reversed by weight reduction.

The finding suggests that patients with renal hyperfiltration might be less likely to experience durable weight reduction, Ji said. “However, few studies have revealed similar observations. Therefore, further validations and investigations are still needed for this finding.”

Furthermore, the team found a positive nonlinear association of serum creatinine with successful weight reduction at 12 months — a finding that will also require additional investigations to examine the mechanism underlying the association.

Overall, Ji concluded that while longer duration of GLP-1 RA treatment using semaglutide, nondiabetic status, and higher percentage of body fat might be associated with better weight reduction, “basal metabolic rate, skeletal muscle mass, muscle mass of the abdomen and limbs, and serum creatinine were nonlinearly associated with the probability of successful weight reduction.”

Randy Seeley, MD, Henry King Ransom Endowed Professor of Surgery, Internal Medicine, and Nutritional Sciences at the University of Michigan School of Medicine, Ann Arbor, Michigan, and director of the National Institutes of Health-funded Michigan Nutrition Obesity Research Center, told Medscape Medical News, “The main results of the study agree with what the field has already seen. Although it is a relatively small study, it corroborates other larger studies,” said Seeley, who was not involved in the study.

This work was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project. Ji reported receiving fees for lecture presentations and for consulting from AstraZeneca, Merck, Metabasis, MSD, Novartis, Eli Lilly and Company, Roche, Sanofi-Aventis, and Takeda. Seeley reported that his lab has worked with both Novo and Lilly (and others trying to enter the space), and he has also served as a paid consultant for both of those companies (and others trying to enter the space).

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.