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Almandoz, J.P.* ; Miras, A.D.* ; Blüher, M. ; Orozco Del Pino, P.* ; Mojdami, D.* ; Batterham, R.L.* ; Trice, K.* ; Goebel, B.* ; Tangi, F.*

Efficacy and safety of orforglipron in adults with body mass index of 27 to less than 30 kg/m2 and adiposity-related complications: A post hoc analysis of the ATTAIN-1 trial.

Obes. Pillars 20:100346 (2026)
Publ. Version/Full Text Research data DOI
Open Access Gold
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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/m2 and adiposity-related complications have not been characterized. Adults with overweight and an adiposity-related complication are at substantial cardiometabolic risk, and obesity medications are recommended for this group. 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/m2 and ≥1 adiposity-related complication. Endpoints included change from baseline to Week 72 the percent change in body weight, BMI, categorical weight-loss, waist circumference, lipids, patient-reported outcomes, and safety. Effect estimates are reported using efficacy and treatment-regimen estimands. Efficacy endpoints were also reported per sex subgroup. 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/m2 and ≥1 adiposity-related complication, orforglipron was associated with improvements in anthropometric and cardiometabolic parameters, with a safety profile broadly consistent with the overall ATTAIN-1 trial (ClinicalTrials.gov identifier: NCT05869903).
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Publication type Article: Journal article
Document type Scientific Article
Keywords Adiposity-related Complication ; Cardiometabolic Risk ; Orforglipron ; Overweight Or Obesity ; Quality Of Life ; Weight Reduction
ISSN (print) / ISBN 2667-3681
e-ISSN 2667-3681
Journal Obesity Pillars
Quellenangaben Volume: 20, Issue: , Pages: , Article Number: 100346 Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG)