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

Powell, W.; Mazzotti, D. R.; Herrmann, S. D.; Davis, A. M.; Mittendorfer, B.; Bruce, J.; Song, X.; Waitman, L. R.

2025-12-02 health informatics
10.64898/2025.12.01.25341393 medRxiv
Show abstract

ImportanceAlthough 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. ObjectiveTo evaluate the effectiveness of semaglutide compared with lifestyle counseling alone for weight loss in diabetic and non-diabetic patients with obesity. DesignA multi-site, retrospective, observational study using data from electronic health records in a time-to-event analysis for comparative effectiveness. SettingsData were collected from 13 health systems across the central United States part of the Greater Plains Collaborative (GPC). ParticipantsAdults with a body mass index greater than or equal to 30 kg/m2 and no prior history of malignant cancer, pregnancy, or bariatric surgery receiving semaglutide or lifestyle counseling alone. ExposuresParticipants 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 MeasuresThe primary outcome was incidence of 10% or greater reduction in weight from baseline. ResultsThere 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 RelevanceThe 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 PointsO_ST_ABSQuestionC_ST_ABSDoes 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? FindingsAfter 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. MeaningCompared 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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