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

Clinical Trial20 Apr 2026Phase 3

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 trial testing orforglipron versus placebo in people with obesity or overweight, with and without type 2 diabetes, measuring HbA1c change as primary endpoint. Enrolling 600 participants with 18-month study duration, part of larger master protocol study. Eli Lilly advances the first approved small-molecule oral GLP-1 into obesity indication, expanding beyond its April 2026 type 2 diabetes approval. This represents a direct challenge to Novo Nordisk's oral semaglutide, which gained FDA approval for obesity in January 2026.

Strategic Signal

Eli Lilly positions orforglipron to compete directly against Novo Nordisk's oral semaglutide in obesity, leveraging its dosing convenience advantage (no fasting requirements). The HbA1c primary endpoint in mixed population suggests targeting metabolic benefits over pure weight loss, potentially differentiating from weight-focused obesity trials. US payers will compare orforglipron's metabolic profile against oral semaglutide's established obesity efficacy when making formulary decisions in 2027-2028.

GLP-1Weight lossType 2 diabetesEli Lilly

Original Abstract

The main purpose of this study is to see how orforglipron, compared with placebo, helps improve glycemic control in participants with obesity or with overweight and 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; Type 2 Diabetes | Primary endpoint(s): Change from Baseline in Hemoglobin A1c (HbA1c) | Enrollment: 600 (estimated) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2027-08 | Status: Active Not Recruiting | Last update: 2026-04-20

View original source ↗

Related signals

Strategic Signal

FDA1 Apr 2026New Drug Approval (NDA/BLA)High impact● 10/10i

FDA Approves Foundayo (Orforglipron) — New Drug Approval (NDA/BLA)

FDA approved orforglipron (Foundayo, Eli Lilly) for type 2 diabetes -- a once-daily oral small-molecule GLP-1 receptor agonist. Orforglipron is the first non-peptide oral GLP-1 approved in the US; oral semaglutide (Rybelsus, Novo Nordisk) has been approved for T2D since 2019 and expanded to obesity in January 2026. Unlike Rybelsus, orforglipron requires no fasting or water volume restrictions before dosing.

GLP-1Type 2 diabetesPricing/accessEli Lilly Novo Nordisk

Strategic Signal

Clinical Trial19 Mar 2026Phase 3High impact● 9/10i

Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)

Phase 3 SURMOUNT-1 tests once-weekly tirzepatide at three doses versus placebo in adults without type 2 diabetes who have obesity or are overweight with comorbidities. The randomized, double-blind trial targets 2,539 participants with primary efficacy assessment at 72 weeks. This represents tirzepatide's pivotal obesity trial against placebo, potentially supporting Eli Lilly's bid to compete directly with Wegovy in the non-diabetic obesity market. A prediabetes subgroup continues long-term to assess diabetes prevention.

Weight lossGLP-1Eli Lilly

Strategic Signal

FDA19 Mar 2026Supplemental Approval: Efficacy [Priority Review]High impact● 9/10i

FDA Approves Imcivree (Setmelanotide): Supplemental Approval: Efficacy [Priority Review]

FDA approved a supplemental application for Imcivree (setmelanotide, Rhythm) on March 19, 2026, under priority review. This represents an efficacy-based label expansion for the melanocortin-4 receptor agonist, which was initially approved for rare genetic obesity disorders. Rhythm gains additional indication breadth in the specialized rare obesity market, where treatment options remain extremely limited. The priority review designation signals FDA recognition of significant unmet medical need in the expanded patient population.

Weight lossOtherRhythm

Strategic Signal

Clinical Trial17 Apr 2026Phase 3High impact● 8/10i

A Phase 3, Open-Label Study of Once Daily LY3502970 Compared With Insulin Glargine in Adult Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk

Phase 3 open-label trial compared once-daily oral orforglipron versus insulin glargine in people with type 2 diabetes and obesity or overweight at increased cardiovascular risk. The study enrolled 2,749 participants with primary endpoint of time to first major adverse cardiovascular event, completed in March 2026. Eli Lilly is positioning orforglipron as a cardiovascular outcomes option in high-risk populations, directly competing with established insulin therapy in this indication. This represents the first cardiovascular outcomes trial for orforglipron following its April 2026 FDA approval for type 2 diabetes.

GLP-1Type 2 diabetesWeight lossCardiovascularEli Lilly