A Randomized, Double-Blind, Phase 3 Study to Investigate the Efficacy and Safety of LY3437943 Once Weekly Compared to Placebo in Participants With Severe Obesity and Established Cardiovascular Disease

ClinicalTrials23 Jul 2025·Phase 3● 8/10i

A Randomized, Double-Blind, Phase 3 Study to Investigate the Efficacy and Safety of LY3437943 Once Weekly Compared to Placebo in Participants With Severe Obesity and Established Cardiovascular Disease

Eli Lilly and Company

Phase 3 randomized, double-blind, placebo-controlled study evaluates retatrutide once weekly in people with severe obesity and established cardiovascular disease. The trial targets 1,800 participants over 113 weeks, with primary endpoint of percent change in body weight from baseline. Eli Lilly is advancing retatrutide, a triple agonist (GLP-1/GIP/glucagon), into a high-risk cardiovascular population that represents a significant commercial opportunity beyond standard obesity treatment. This positions retatrutide as a potential competitor to Wegovy, which gained cardiovascular risk reduction approval in March 2024 for people with obesity and established CVD.

Strategic signal

Eli Lilly is directly challenging Novo Nordisk's cardiovascular positioning with Wegovy by testing retatrutide in the same high-value population of people with obesity and established CVD. This head-to-head competitive dynamic will likely intensify cardiovascular outcomes messaging and could fragment the premium-priced obesity market where Wegovy currently holds the cardiovascular risk reduction claim. US payers and cardiology societies will watch closely, as cardiovascular outcomes data historically drives formulary preference and specialist adoption in this population.

Weight lossCardiovascularGLP-1Eli Lilly

Original Abstract

The main purpose of this study is to evaluate the efficacy and safety of retatrutide once weekly in participants with obesity and established cardiovascular disease (CVD). The study will last about 113 weeks. | Condition(s): Obesity; Cardiovascular Diseases | Primary endpoint(s): Percent Change from Baseline in Body Weight | Enrollment: 1,800 (estimated) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2026-04 | Status: Active Not Recruiting | Last update: 2025-07-23

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