| Abstrakt: |
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 over week 20‐68 with continued semaglutide, but deteriorated following the switch to placebo (p <.001 [week 20‐68]). Net reductions in antihypertensive/lipid‐lowering medication use occurred with semaglutide versus placebo (both trials). Conclusions: Semaglutide may improve cardiometabolic risk factors and reduce antihypertensive/lipid‐lowering medication use versus placebo in adults with overweight/obesity without diabetes. These potential benefits were not maintained after treatment discontinuation. ClinicalTrials.gov numbers STEP 1 NCT03548935, STEP 4 NCT03548987. [ABSTRACT FROM AUTHOR] |
Plný text