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

ClinicalTrials20 Apr 2026·Phase 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

FDA1 Apr 2026·New Drug Approval (NDA/BLA)● 10/10iHigh impact

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

ClinicalTrials19 Mar 2026·Phase 3● 9/10iHigh impact

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

ClinicalTrials17 Apr 2026·Phase 3● 8/10iHigh impactPick of the week

The Effect of Semaglutide in Subjects With Non-cirrhotic Non-alcoholic Steatohepatitis

Phase 3 trial evaluates semaglutide versus placebo in adults with non-cirrhotic NASH, measuring steatohepatitis resolution, fibrosis improvement, and cirrhosis-free survival over approximately 5 years. The study enrolled 1,205 adults and is active but not recruiting, with completion expected in 2029. This represents Novo Nordisk's push into NASH, a major unmet need with no approved GLP-1 therapies despite strong preclinical rationale. The trial's dual primary endpoints and 5-year duration suggest preparation for a pivotal regulatory filing in this large addressable market.

GLP-1Liver/NASHNovo Nordisk

ClinicalTrials17 Apr 2026·Phase 3● 8/10iHigh impact

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Retatrutide Once Weekly in Participants Who Have Obesity or Overweight and Chronic Low Back Pain

Phase 3 trial evaluating retatrutide for chronic low back pain in people with obesity or overweight, targeting dual primary endpoints of pain intensity reduction and weight loss. 586-person placebo-controlled study expected to complete September 2027, investigating a novel indication beyond traditional metabolic endpoints. Eli Lilly is exploring pain management as a potential expansion for their triple agonist, representing the first major trial of a GLP-1-based therapy specifically for chronic pain conditions.

GLP-1Weight lossOtherEli Lilly