Sex, Comorbidities Linked to Semaglutide Weight Loss Trajectories

In a real-world study of 36,647 adults receiving injectable semaglutide (Wegovy), investigators identified baseline factors associated with weight loss trajectories, including sex, cardiometabolic comorbidities, and prior challenges with weight consistency.

The poster was presented at the Endocrine Society (ENDO) 2026 Annual Meeting in Chicago, Illinois, by senior author Hans Johnson, MBChB, MRes, MSc, of the University of Bristol, and co-authors from Voy and Boston Children’s Hospital. The study aimed to characterize real-world patterns of weight loss ancand identify factors that may inform individualized prediction tools.

“Whilst weight loss outcomes with injectable semaglutide are well characterised in randomised trials, emergent evidence suggests that the magnitude of weight loss with GLP-1 receptor agonists may be associated with baseline comorbidities,” wrote Johnson and colleagues. “Understanding factors associated with weight loss outcome variation could inform the development of individualised prediction tools.”

Investigators conducted a retrospective open cohort analysis of adults initiating injectable semaglutide through a UK-based digital weight loss service. Cox proportional hazards models and mixed-effects models were used to evaluate factors associated with weight loss outcomes. Data extraction occurred in November 2025.

The final analysis cohort included 36,647 adults with a mean age of 45.76 years. Of these, 7,077 (19.31%) had 6-month follow-up data and 2,329 (6.36%) had 12-month follow-up data available.

Women were more likely than men to achieve ≥20% total body weight loss at 12 months (Hazard Ratio [HR], 1.93; P <.001).

Several baseline comorbidities were associated with a lower likelihood of achieving ≥20% total body weight loss at 12 months, including diabetes (HR, 0.71; P <.001), hypercholesterolemia (HR, 0.76; P <.001), hypertension (HR, 0.76; P <.001), and sleep apnea (HR, 0.62; P <.001). No significant associations were observed for metabolic dysfunction-associated fatty liver disease or asthma.

In multivariate mixed-effects models evaluating 12-month weight loss trajectories, prior challenges with weight consistency, erectile dysfunction, polycystic ovary syndrome, and sleep apnea were significantly associated with lower percentage weight loss during semaglutide treatment.

Investigators noted that baseline clinical and behavioral factors may help “pattern” weight loss responses in real-world semaglutide use. They added that factors influencing treatment persistence may also contribute to observed variability in outcomes, representing a potential source of bias. Future research should consider integrating these variables into clinical prediction tools to support counseling, goal setting, and treatment decision-making.

“Future research should consider integrating these factors into clinical prediction tools to provide individualised estimates of the benefits of semaglutide. These could be beneficial for counselling, expectation/goal setting and treatment decisions,” investigators concluded.

References

1. Johnson H, Clift AK, Reisel D, Huang D, Reis B. Baseline predictors of real-world weight loss outcomes with injectable semaglutide: cohort analysis of over 36,000 individuals. Poster presented at: ENDO 2026 Annual Meeting; June 14, 2026; Chicago, IL.

2. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183