A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Tablet Once Daily Compared With Placebo in Participants With Obesity or Overweight With and Without Type 2 Diabetes

ClinicalTrials16 Apr 2026·Phase 3● 7/10i

A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Tablet Once Daily Compared With Placebo in Participants With Obesity or Overweight With and Without Type 2 Diabetes

Eli Lilly and Company

Orforglipron, Eli Lilly's oral small-molecule GLP-1 receptor agonist, is being tested against placebo for weight management in people with obesity or overweight without type 2 diabetes. The phase 3 trial targets 600 participants over 18 months, measuring percent change in body weight as the primary endpoint. This represents Eli Lilly's push to expand orforglipron beyond its April 2026 FDA approval for type 2 diabetes into the weight management market, competing directly with Novo Nordisk's approved oral semaglutide for obesity. The trial is part of a broader master protocol evaluating orforglipron across multiple obesity-related populations.

Strategic signal

Eli Lilly is racing to establish orforglipron in weight management before Novo Nordisk's oral semaglutide dominates the oral obesity market following its January 2026 approval. This trial specifically targets people without diabetes, positioning orforglipron as a first-line oral option for weight management rather than just diabetes spillover. The 18-month timeline suggests data by late 2027, potentially enabling a 2028 obesity filing if successful.

GLP-1Weight lossEli Lilly

Original Abstract

The main purpose of this study is to see how orforglipron, compared with placebo, helps reduce body weight in participants with obesity or with overweight and at least one other related health condition (excluding type 2 diabetes). This trial is part of the master protocol study J2A-MC-GZPO (NCT06993792). Participation in the study will last about 18 months. | Condition(s): Obesity; Overweight | Primary endpoint(s): Percent Change from Baseline in Body Weight | Enrollment: 600 (estimated) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2027-08 | Status: Recruiting | Last update: 2026-04-16

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