Predictors of Peak Body Weight Loss With Semaglutide in the SELECT Trial.

OBJECTIVE: To evaluate whether clinically available baseline characteristics predict peak percentage body weight loss (%BWL) achieved with chronic use of semaglutide. RESEARCH DESIGN AND METHODS: SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity Trial) evaluated the cardiovascular benefits of semaglutide in adults (mean age 62, 72% men) with obesity and preexisting atherosclerotic disease without diabetes. This prespecified analysis evaluated participants randomized to semaglutide who continued treatment for a minimum of 1 year. Baseline demographics, medical history, laboratory variables, and clinical measurements were candidate predictors of peak %BWL evaluated in a general linear model estimated with ordinary least squares. RESULTS: Among the 7,594 SELECT participants continuously treated with semaglutide for ≥1 year (representing 86.3% of those randomized to semaglutide), median peak %BWL was 12.5% (interquartile range [IQR] 7.9-17.9), achieved after a median of 19 months (IQR 10-30) of treatment. The full model predicted <10% of the variability in peak %BWL; female sex accounted for 85.3% of this model (explaining ≈8% of the variability). Semaglutide dose was associated with peak %BWL (median 6.0% [IQR 1.9-10.9] vs. 13.3% [IQR 9.0-18.4] for those with a maximum dose of 0.24 mg vs. 2.4 mg). The highest median peak %BWL was achieved by women (16.6% [IQR 10.9-23.4]) versus men (12.4% [IQR 8.4-16.9]). CONCLUSIONS: The peak amount of weight loss expected following initiation of semaglutide cannot be predicted based on clinically available baseline characteristics; unmeasured biological, behavioral, or genetic differences are likely responsible for variability in individual response. Women treated with the highest dose of semaglutide experienced the largest %BWL.