Background: Management guidelines for obesity suggest maintaining a minimum of 5% body weight reduction to help prevent or lower the risk of developing conditions such as hypertension and type 2 diabetes. However, achieving long-term weight control is difficult with lifestyle modification alone, making it essential to combine pharmacotherapy with diet and exercise in individual cases. Semaglutide 2.4 mg has demonstrated significant reductions in body weight and cardiometabolic risk factors in clinical trials, but information on outcomes in a real-world setting is limited.

Objective: To assess changes in body weight and other clinical outcomes at 6-month follow-up among adults on semaglutide 2.4 mg in a real-world setting in the United States (US).

Methods: Observational and retrospective cohort study of patients initiating treatment between 15 June 2021, and 31 March 2022, using a large US claims-linked electronic health record database.

Results: Mean (±SD) body mass index (BMI) of the 343 patients included in the analysis was 37.9 ± 5.5 kg/m. After 6 months, mean body weight change was -10.5 ± 6.8 kg (95% CI: -11.2; -9.8,  < 0.001) and mean percentage body weight change was -10.0% ± 6.6% (95% CI: -10.7; -9.3,  < 0.001). Most (79.0%) patients had ≥5% body weight reduction, 48.1% had ≥10% body weight reduction, and 19.0% had ≥15% body weight reduction. Among patients with available data, the mean change in HbA1c ( = 30) was -0.6% ± 1.2% (95% CI: -1.0; -0.1,  = 0.016) and nearly two-thirds of patients with prediabetes or diabetes at baseline reverted to normoglycemia. Mean reductions of -4.4 ± 12.3 mmHg (95% CI: -5.7; -3.0,  < 0.001) and -1.7 ± 8.4 mmHg (95% CI: -2.6; -0.7,  < 0.001) were observed in systolic and diastolic blood pressure, respectively ( = 307). Statistically significant reductions in mean total cholesterol (-12.2 ± 38.8 mg/dl [95% CI: -24.3 to -0.06,  < 0.049]) and triglycerides (-18.3 ± 43.6 mg/dl [95% CI: -4.7; -31.9,  < 0.009]) were also observed ( = 42).

Conclusions: This study demonstrated the effectiveness of semaglutide 2.4 mg in reducing body weight and improving cardiometabolic parameters in adults with overweight or obesity in a real-world clinical practice setting, showing a significant mean body weight reduction and improvements in biomarkers like blood pressure and HbA1c over a 6-month period. These findings, aligning with previous clinical trials at comparable time points, highlight the clinical relevance of semaglutide as an effective therapeutic option for obesity.

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