Comparison of semaglutide and lifestyle counseling for weight loss using electronic health records

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Abstract Importance Although it is well-established that GLP-1 receptor agonists are highly effective in causing marked weight loss in randomized controlled trials, there is a need to evaluate their effectiveness in real-world settings and compare it with the outcomes of traditional lifestyle counseling. Objective To evaluate the effectiveness of semaglutide compared with lifestyle counseling alone for weight loss in diabetic and non-diabetic patients with obesity. Design A multi-site, retrospective, observational study using data from electronic health records in a time-to-event analysis for comparative effectiveness. Settings Data were collected from 13 health systems across the central United States part of the Greater Plains Collaborative (GPC). Participants Adults with a body mass index greater than or equal to 30 kg/m 2 and no prior history of malignant cancer, pregnancy, or bariatric surgery receiving semaglutide or lifestyle counseling alone. Exposures Participants received either lifestyle counseling alone with at least three sessions within the first 16 weeks or were prescribed semaglutide for a minimum of 16 weeks. Main Outcome and Measures The primary outcome was incidence of 10% or greater reduction in weight from baseline. Results There were 3,927 eligible participants, with 615 taking semaglutide and 3,312 receiving lifestyle counseling. Following propensity score matching, each group (diabetic and non-diabetic) consisted of 120 and 495 participants respectively. Hazard ratios for 10% weight loss were significantly higher from semaglutide than for lifestyle counseling for non-diabetic (hazard ratio, 1.63 [95% CI: 1.32, 2.01; p<0.001]) and diabetic (hazard ratio, 2.45 [95% CI: 1.47, 4.09; p<0.001]) populations. Conclusion and Relevance The data from our study suggest that adjunct semaglutide therapy compared with lifestyle counseling alone is more effective in achieving at least 10% weight loss. This information may be used to inform clinical practice guidelines and stimulate future research on the long-term weight loss effectiveness of this class of drugs. Key Points Question Does semaglutide, a novel glucagon-like peptide-1 receptor agonist, improve weight loss outcomes compared to lifestyle counseling alone in patients with obesity in a real-world setting? Findings After adjusting for possible confounders, patients treated with semaglutide had a greater incidence and speed of achieving 10% weight loss compared to those receiving lifestyle counseling alone. Meaning Compared with lifestyle counseling alone, semaglutide is a more effective weight loss option for patients with obesity. Future studies should determine the cost-benefit ratio, broader health benefits, and long-term weight loss maintenance of semaglutide therapy compared to or combined with lifestyle counseling.

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