Effective weight reduction has been demonstrated with semaglutide 2.4 mg in global populations; however, evidence in East Asian populations particularly, those with lower BMI thresholds, is limited. STEP 12 is the first trial conducted in a Chinese population evaluating semaglutide 2.4 mg in adults with overweight or obesity, with or without type 2 diabetes (T2D), defined using lower BMI cutoffs. This subgroup analysis investigated the efficacy by T2D status and BMI <27 kg/m2 as cutoff.

In this phase 3b, double-blind, placebo-controlled trial, participants with overweight (BMI ≥24 to <28 kg/m2 plus ≥1 weight-related complication) or obesity (BMI ≥28 to <30 kg/m2) were randomised 2:1 to semaglutide 2.4 mg or placebo, plus lifestyle intervention for 44 weeks (including a 16-week dose escalation). Subgroup analyses, based on T2D status and BMI 27 kg/m2 cutoff assessed confirmatory endpoints: change (%) in body weight (BW), waist circumference (WC) and odds of achieving a ≥5% BW reduction. Results used the treatment policy estimand.

A total of 242 participants (mean age 41years and BMI of 27.9 kg/m2) were randomised to semaglutide 2.4 mg (n=161) or placebo (n=81), including 47 (19%) with T2D and 195 (81%) without T2D. At week 44, mean BW change was −7.96% with semaglutide vs −0.59% with placebo in T2D (ETD −7.36%-points, 95% CI −11.64, −3.09), and −13.06% vs −2.58% without T2D (ETD −10.48%-points, 95% CI −12.61, −8.36), with no significant treatment by T2D interaction (p=0.20) (Fig. 1). For BMI <27 kg/m², BW changes were −7.43% vs −0.12% in T2D and −13.21% vs −5.52% without T2D, again with no significant interaction (p=0.93). WC reductions: ETD −4.84 cm for T2D and −7.02 cm for non-T2D with no significant interaction. Odds of achieving ≥5% BW loss were markedly higher with semaglutide: OR 11.68 for T2D and 15.49 for non-T2D. Similar patterns occurred in BMI <27 kg/m2 subgroup.

In Chinese adults with overweight or obesity defined by local BMI thresholds, semaglutide 2.4 mg provided substantial reductions in BW and WC versus placebo in participants with and without T2D. Efficacy remained at lower BMI irrespective of T2D, with numerically greater reductions in non T2D participants.