Effect of semaglutide 2.4 mg once weekly on 10‐year type 2 diabetes risk in adults with overweight or obesity

Abstract Objective In the Semaglutide Treatment Effect in People with obesity (STEP) trials, once‐weekly subcutaneous semaglutide 2.4 mg plus lifestyle intervention reduced body weight and improved cardiometabolic parameters in adults with obesity (or overweight with weight‐related comorbidities). Effects on the risk of developing type 2 diabetes (T2D) require investigation. Methods STEP 1 (68 weeks) and 5 (104 weeks) randomized participants to semaglutide 2.4 mg or placebo. STEP 4 included a 20‐week semaglutide run‐in followed by randomization to 48 weeks of continued semaglutide or withdrawal (placebo). Ten‐year T2D risk scores were calculated post hoc using Cardiometabolic Disease Staging. Results In STEP 1 ( N = 1583), relative risk score reductions were greater with semaglutide versus placebo (semaglutide: −61.1%; placebo: −12.9%; p < 0.0001). These reductions were maintained to week 104 in STEP 5 ( N = 295; semaglutide: −60.0%; placebo: 3.5%; p < 0.0001). Risk scores during the STEP 4 run‐in period ( N = 776) were reduced from 20.6% to 11.1% and further to 7.7% at week 68 with continued semaglutide, increasing to 15.4% with withdrawal (relative risk score change: semaglutide: −32.1%; placebo: +40.6%; p < 0.0001). Risk score reductions mirrored weight loss. Conclusions Cardiometabolic Disease Staging risk assessment suggests that once‐weekly semaglutide 2.4 mg may substantially lower 10‐year T2D risk in people with overweight or obesity. image