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
5 affiliations
- 1Department of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- 2School of Medicine, Faculty of Life & Health Sciences, Ulster University, UK
- 3Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Center Munich, Leipzig University and University of Leipzig Medical Center, Leipzig, Germany
- 4University of Leipzig Medical Center, Leipzig, Germany
- 5Eli Lilly and Company, Indianapolis, IN, USA
Abstract
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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BibTeX
@article{almandoz2026efficacy,
title = {{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}},
author = {Jaime P. Almandoz and Alexander Dimitri Miras and Matthias Blüher and Pedro Orozco Del Pino and Donna Mojdami and Rachel L. Batterham and Kevin Trice and Benjamin Goebel and Fatih Tangi},
journal = {Obesity Pillars},
year = {2026},
month = oct,
doi = {10.1016/j.obpill.2026.100346},
url = {https://doi.org/10.1016/j.obpill.2026.100346},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Jaime P. Almandoz
AU - Alexander Dimitri Miras
AU - Matthias Blüher
AU - Pedro Orozco Del Pino
AU - Donna Mojdami
AU - Rachel L. Batterham
AU - Kevin Trice
AU - Benjamin Goebel
AU - Fatih Tangi
PY - 2026
DA - 2026/10/14
JO - Obesity Pillars
DO - 10.1016/j.obpill.2026.100346
UR - https://doi.org/10.1016/j.obpill.2026.100346
AB - 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).
SN - 2667-3681
ER -