Randomized trial · 2023

Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses.

MN Kosiborod, M Bhatta, M Davies, JE Deanfield, WT Garvey, U Khalid, R Kushner, DM Rubino. Diabetes, obesity & metabolism.

AIMS: Evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on cardiometabolic risk factors in people with overweight/obesity without diabetes in the STEP 1 and 4 trials. MATERIALS AND METHODS: STEP 1 and 4 were phase III, 68-week, placebo-controlled trials of once-weekly semaglutide 2.4 mg combined with lifestyle intervention; STEP 4 had a 20-week semaglutide run-in and 48-week randomized withdrawal period. Participants had a body mass index ≥30 kg/m2 or ≥27 kg/m2 with one or more weight-related comorbidity, without diabetes. Pre-specified endpoints were changes in waist circumference, systolic/diastolic blood pressure (SBP/DBP), lipids, fasting plasma glucose (FPG), fasting serum insulin and antihypertensive/lipid-lowering medication use. Post-hoc assessments included non-high-density lipoprotein (HDL) cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR; STEP 1 only), atherosclerotic cardiovascular disease (ASCVD) risk (American College of Cardiology/American Heart Association algorithm; STEP 1 only) and cardiometabolic risk factors by weight loss achieved (<5%, 5% to <10%, 10% to <15%, or ≥15%) (STEP 1 only). RESULTS: Of the 1961 participants in STEP 1 and 803 in STEP 4, most had one or more complication/comorbidity at baseline, with dyslipidaemia and hypertension most prevalent. In STEP 1, reductions in waist circumference, SBP, DBP, FPG, fasting serum insulin, lipids and HOMA-IR were greater with semaglutide versus placebo (p ≤ .001). Reductions in SBP, non-HDL cholesterol, low-density lipoprotein cholesterol and FPG were generally greater with semaglutide than placebo within weight-loss categories. Non-significant ASCVD risk reductions were observed with semaglutide versus placebo (p > .05). In STEP 4, improvements in waist circumference, SBP, FPG, fasting serum insulin and lipids during the semaglutide run-in (week 0-20) were maintained ov

Open sourcedoi:10.1111/dom.14890PMID 36200477