Obesity

GLP-1s fall short in real-world obesity care compared with clinical trials

June 12, 2025

Real-world weight and glycemic improvements with semaglutide or tirzepatide are substantially lower than those reported in phase 3 trials, likely due to high discontinuation rates and suboptimal dosing. These findings underscore the importance of sustained therapy and adequate dosing to maximize clinical benefit in obesity pharmacotherapy.

Study details: A retrospective cohort study evaluated 7,881 adults with overweight or obesity (without T2DM) who initiated injectable semaglutide (n = 6,109) or tirzepatide (n = 1,772) between 2021 and 2023 in a large U.S. health system. Discontinuation was defined as a >90-day gap in therapy and categorized as early (within 3 months) or late (3–12 months).

Results: At 12 months, mean weight reduction was 8.7% overall. Weight loss was attenuated with early discontinuation (3.6%), intermediate with late discontinuation (6.8%), and greatest with continued therapy (11.9%) (p<0.001). Among those with prediabetes, mean absolute HbA1c reduction at 1 year was 0.1% (early discontinuation), 0.2% (late), and 0.4% (non-discontinuation) (p<0.001). Notably, 80.8% of patients were maintained on low dosages.

Source:

Gasoyan H, et al. (2025, June 10). Obesity. Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. https://pubmed.ncbi.nlm.nih.gov/40491239/