Effects of Semaglutide on Cardiometabolic Risk in People with Obesity, With and Without Type 2 Diabetes: A Retrospective Observational Study.

: Obesity and insulin resistance are major contributors to cardiometabolic disease and type 2 diabetes mellitus (T2DM). This study evaluated the real-world effects of semaglutide on metabolic parameters, body composition, and cardiometabolic risk factors in people with obesity, with and without T2DM, and explored predictors of treatment response. : This retrospective longitudinal observational study included 70 adults with obesity (42 with T2DM and 28 without T2DM) treated with semaglutide according to current clinical guidelines. The primary outcomes were changes in body weight, waist circumference, fasting plasma glucose, and glycated hemoglobin (HbA1c). Secondary outcomes included changes in lipid profile, insulin resistance indices, inflammatory markers, hepatic parameters, and body composition assessed by bioelectrical impedance analysis (InBody770). : Semaglutide treatment was associated with significant reductions in body weight (-9 kg), waist circumference (-8 cm), HbA1c (-1.1%), systolic blood pressure (-7.5 mmHg), visceral fat area (-30.1 cm), and insulin resistance markers. Improvements in glycemic parameters were more pronounced in participants with T2DM. Skeletal muscle mass (SMM) was relatively preserved during treatment. Baseline HbA1c and visceral adiposity were independently associated with metabolic response. : In this real-world observational cohort, semaglutide was associated with significant improvements in metabolic parameters, body composition, and cardiometabolic risk markers in people with obesity, with and without T2DM. Baseline metabolic characteristics may influence treatment response.