A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral Orforglipron Compared With Placebo in Adult Participants With Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-1)

ClinicalTrials5 Nov 2025·Phase 3● 8/10i

A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral Orforglipron Compared With Placebo in Adult Participants With Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-1)

Eli Lilly and Company

ATTAIN-1 is testing orforglipron, Eli Lilly's oral small-molecule GLP-1 receptor agonist, versus placebo in 3,127 adults with obesity or overweight with weight-related comorbidities. This 72-week phase 3 trial with 2-year extension for people with prediabetes is placebo-controlled and has completed enrollment. Eli Lilly is building the clinical foundation for orforglipron in obesity, following its April 2026 FDA approval for type 2 diabetes where it differentiated from Novo Nordisk's oral semaglutide with no dosing restrictions. This represents Eli Lilly's entry into oral GLP-1 obesity treatment, directly challenging Novo Nordisk's pending high-dose oral semaglutide for obesity approved in January 2026.

Strategic signal

Eli Lilly is positioning orforglipron as the differentiated oral GLP-1 for obesity, leveraging convenience advantages over Rybelsus's fasting requirements. FDA approval would create the first small-molecule oral GLP-1 for obesity, potentially commanding premium pricing given the convenience profile. Payers will evaluate orforglipron's weight loss efficacy against Novo Nordisk's established oral semaglutide data, with dosing convenience likely driving formulary positioning debates. This sets up direct oral GLP-1 competition in obesity, where injection-averse patients represent significant unmet demand.

GLP-1Weight lossEli Lilly Novo Nordisk

Original Abstract

This study will investigate the efficacy and safety of once daily oral orforglipron in adult participants with obesity or overweight with weight-related comorbidities. The study has two phases: a main phase and an extension phase. The main phase of the study lasted 72 weeks. Participants with prediabetes will continue in the extension for another 2 years. | Condition(s): Obesity; Overweight; Overweight or Obesity | Primary endpoint(s): Mean Percent Change from Baseline in Body Weight | Enrollment: 3,127 (actual) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2025-07-25 | Status: Active Not Recruiting | Last update: 2025-11-05

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