A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants With Hypertension and Obesity or Overweight: Randomized, Double-Blind, Placebo-Controlled Trials (ATTAIN-HYPERTENSION)

ClinicalTrials24 Mar 2026·Phase 3● 7/10i

A Master Protocol to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants With Hypertension and Obesity or Overweight: Randomized, Double-Blind, Placebo-Controlled Trials (ATTAIN-HYPERTENSION)

Eli Lilly and Company

Phase 3 master protocol evaluates once-daily orforglipron for hypertension treatment in people with obesity or overweight across two independent studies. The placebo-controlled framework targets 974 participants with completion expected September 2027. Eli Lilly is expanding orforglipron beyond its approved type 2 diabetes indication, testing the first small-molecule oral GLP-1 in cardiovascular indication territory dominated by Novo Nordisk's Wegovy. This represents a direct challenge to semaglutide's expanding label into cardiometabolic conditions.

Strategic signal

Eli Lilly is leveraging orforglipron's oral convenience advantage to contest Novo Nordisk's cardiovascular territory expansion. While Wegovy secured MACE reduction approval in March 2024, hypertension represents a broader primary prevention market where oral dosing could drive adoption. US commercial teams will likely position this against injectable GLP-1s for treatment-naive hypertensive patients, similar to how oral semaglutide carved diabetes market share despite lower efficacy. Success here could establish a beachhead for orforglipron in multiple cardiometabolic indications.

GLP-1CardiovascularWeight lossEli Lilly

Original Abstract

The GZPL master protocol will support 2 independent studies, J2A-MC-GZL1 (GZL1) and J2A-MC-GZL2 (GZL2). The purpose of this study is to create a framework to evaluate the safety and efficacy of orforglipron for the treatment of hypertension in participants with obesity or overweight. | Condition(s): Hypertension | Primary endpoint(s): Number of Participants Allocated to Each ISA | Enrollment: 974 (estimated) | Phase: Phase 3 | Sponsor: Eli Lilly and Company | Expected completion: 2027-09 | Status: Recruiting | Last update: 2026-03-24

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