Semaglutide 2.4 mg Clinical Outcomes in Patients with Obesity or Overweight: A Real-World Retrospective Comparative Cohort Study.

INTRODUCTION: This study compared the effectiveness of semaglutide 2.4 mg vs. no treatment with obesity medication (OM) for reducing weight and improving cardiometabolic risk factors among adults with obesity or overweight. METHODS: This real-world, retrospective, observational cohort study included adults with obesity or overweight with ≥ 1 obesity-related complication treated with semaglutide 2.4 mg identified in a large US claims and medical record database (December 15, 2020, through May 30, 2024). Patients were matched 1:4 to non-treated patients using a propensity score (PS) model. Change in weight and body mass index (BMI) (primary outcomes) and changes in cardiometabolic risk factors (secondary outcomes; systolic blood pressure [SBP], diastolic blood pressure [DBP], glycated hemoglobin [HbA1c], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) were assessed from baseline to 12 months. PS matching and generalized linear models were used to compare outcomes. RESULTS: A total of 8,857 semaglutide 2.4 mg-treated patients were matched to 35,428 non-treated patients. After matching, baseline characteristics between cohorts were well balanced in mean age (47.6 vs. 47.8 years), mean BMI (36.7 kg/m in both cohorts), and gender (76% vs. 77% female). Weight data were available for 4,038 and 1,186 patients in the non-treated and semaglutide cohort, respectively. Estimated treatment differences between cohorts showed the semaglutide 2.4 mg cohort had significantly greater percentage (- 15.0%) and absolute reduction in weight (- 15.7 kg), greater reduction in BMI (- 4.2 kg/m), and significantly greater improvements in cardiometabolic risk factors, including SBP (- 6.7 mmHg), DBP (- 2.7 mmHg), HbA1c (- 0.5%), HDL-C (1.2 mg/dl), LDL-C (- 10.4 mg/dl), and triglycerides (- 34.3 mg/dl) at 12 months. CONCLUSION: In this real-world study, adults with obesity or overweight treated with semaglutide 2.4 mg had greater reductions in weight and improvements in cardiometabolic risk factors compared with patients not treated with OM at 12 months. A Graphical Abstract is available for this article.