Efficacy and safety of orforglipron in adults with body mass index of 27 to less than 30 kg/m

Background: Orforglipron, an oral small-molecule glucagon-like peptide-1 receptor agonist, improved body weight and cardiometabolic parameters in the phase 3 ATTAIN-1 trial, but its efficacy and safety in adults with body mass index (BMI) of ≥27 to <30 kg/m Methods: This was a post-hoc analysis of the ATTAIN-1 trial (NCT05869903), a phase 3, randomized, double-blind, placebo-controlled trial in which adults without diabetes and with obesity or overweight were randomized 3:3:3:4 to once-daily oral orforglipron 5.5, 9, or 17.2 mg or placebo for 72 weeks. The present analysis included the subset of randomized participants with BMI ≥27 to <30 kg/m Results: This analysis included 260 participants (orforglipron 5.5 mg: 56; 9 mg: 64; 17.2 mg: 62; placebo: 78). At Week 72, orforglipron was associated with greater mean percent body weight reduction (17.2 mg: -13.5%) versus placebo (-0.3%) (nominal p < 0.001). Females experienced up to -18.8% mean body weight reduction and males up to -10.0%. Orforglipron was associated with improvements in waist circumference, triglycerides, and low-density lipoprotein cholesterol, as well as improvements in patient-reported outcomes. Safety profile was consistent with previous trials with predominantly mild-to-moderate gastrointestinal events. Conclusion: In this post hoc analysis of ATTAIN-1, participants with BMI ≥27 to <30 kg/m