Treatment with semaglutide 2.4 mg leads to improvements in cardiometabolic risk factors in the step 1 trial

We evaluated the effect of semaglutide vs placebo on cardiometabolic (CM) risk factors in STEP 1. STEP 1 (NCT03548935) was a randomized (2:1), double blind, PBO -controlled trial; 1961 adults with overweight/obesity without diabetes, received once-weekly (OW) subcutaneous semaglutide 2.4 mg or placebo, both plus lifestyle intervention, for 68 weeks (wks). Primary endpoints were percent change in body weight (BW) and proportion of subjects achieving ≥5% BW reduction. Secondary endpoints included change in CM risk factors. Post hoc analyses evaluated change in non-high-density lipoprotein (non-HDL) cholesterol and Homeostatic Model Assessment of Insulin Resistance. Estimated mean BW reductions with semaglutide vs placebo were -14.9 vs -2.4% (estimated treatment difference [ETD], -12.44; p< 0.0001). More subjects achieved ≥5% BW reduction with semaglutide vs placebo (86.4 vs 31.5%; ETD, 11.22; p< 0.0001). Semaglutide improved CM risk factors vs placebo: waist circumference (-13.54 vs -4.13 cm), systolic (-6.16 vs -1.06 mmHg) and diastolic blood pressure (-2.83 vs -0.42 mmHg), triglycerides (-22 vs -7%), non-HDL cholesterol (-6 vs -1%), C-reactive protein (-53 vs -15%) and fasting plasma glucose (-8.35 vs -0.48 mg/dL) (Table); p< 0.0001 for all estimated treatment differences/ratios. Semaglutide 2.4 mg OW treatment for 68 weeks led to superior BW reductions and greater improvements in CM risk factors, vs placebo, suggesting favorable CM effects of semaglutide beyond BW loss.