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● 8/10i

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

Phase 3 master protocol testing oral orforglipron versus placebo in adults with obesity or overweight, with or without type 2 diabetes. Enrolling 1,200 participants across two sub-studies, expected completion August 2027, placebo-controlled design. Eli Lilly advances orforglipron into obesity treatment following its April 2026 FDA approval for type 2 diabetes, representing the first small-molecule oral GLP-1 to enter weight management. This positions Eli Lilly to challenge Novo Nordisk's dominance in oral GLP-1 obesity treatment, where oral semaglutide gained approval in January 2026.

Strategic signal

Eli Lilly targets the oral obesity market just eight months after Novo Nordisk's oral semaglutide approval, accelerating competitive pressure in oral weight management. Orforglipron's dosing convenience advantage over Rybelsus (no fasting restrictions) becomes critical for commercial differentiation. US payers will face the first oral GLP-1 obesity competition, potentially creating formulary leverage that didn't exist with injectable options alone.

GLP-1Weight lossType 2 diabetesEli Lilly Novo Nordisk

Original Abstract

The purpose of this Master Protocol is to support two studies to see how well and how safely orforglipron works compared to placebo in participants who have obesity or overweight with or without type 2 diabetes. Participants will be screened for about 4 weeks, after which they will enroll into either J2A-MC-GZP1, NCT06972459 (do not have type 2 diabetes) or J2A-MC-GZP2, NCT06972472 (have type 2 diabetes). | Condition(s): Obesity; Overweight; Type 2 Diabetes | Primary endpoint(s): Number of Participants Allocated to Each Study | Enrollment: 1,200 (estimated) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2027-08 | Status: Recruiting | Last update: 2026-04-16

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