Real-world semaglutide in obesity cohort: effectiveness, safety and persistence across sex, BMI, and prior GLP-1RA treatment

Background: Semaglutide has shown significant efficacy in several clinical trials for the treatment of obesity. However, real-world data on early weight loss and metabolic response in obesity without diabetes cohort are still limited, particularly with respect to individual patient factors. This study aims to evaluate the realworld effectiveness of semaglutide on anthropometric and metabolic parameters in an obesity cohort, including weight loss (kg and percent) and the percentage of participants achieving the 5%, 10% and 15% weight loss targets at mean 3-month, 6-month and 12-month follow-up. In addition, an assessment of safety and reasons for discontinuation, and sub-analyses of anthropometric outcomes by prior liraglutide exposure, sex, and BMI categories will be included. Methods: In this retrospective study, data were collected from adults with overweight/ obesity without diabetes treated with weekly subcutaneous semaglutide for at least 3 months and analyzed at 2-4 (T1), 5-8 (T2), and 9-15 (T3) months of follow-up. Results: Among 248 patients (55.0 years, 34.8 kg/m2 , 77.5% female), only 10.4% and 5.7%, respectively, discontinued due to non-severe gastrointestinal adverse events or cost. Significant weight loss (WL), %WL goal attainment, and improvements in adiposity and metabolic outcomes, including hepatic steatosis, fibrosis, and visceral adiposity indices, were observed at all follow-up visits. Early metabolic improvements occurred regardless of %WL≥5 target. Reduced early anthropometric response in switchers (24%) vs. naive subjects with similar one-year outcomes and no significant differences by sex or baseline BMI category were observed. Conclusions: These results confirm semaglutide’s effectiveness on cardiometabolic risk in real-world obesity management, with a safety profile and early metabolic effects independent of weight loss. The reduced early response in switchers and at low doses highlights the importance of dose optimization to prevent suboptimal initial outcomes after switching. The lack of differences by sex and BMI category supports further studies stratifying patients by age and metabolic risk rather than BMI alone. Low persistence highlights the need for structured, patient-centered support to improve adherence and a better understanding of the drivers of discontinuation.