TRIUMPH-2: Retatrutide in Obesity With Type 2 Diabetes (Results)

Study Overview

TRIUMPH-2 is the Phase 3 trial of retatrutide for weight management in adults who have both type 2 diabetes and obesity or overweight. It is one of the four numbered TRIUMPH trials and, together with TRIUMPH-1 (obesity without diabetes), TRIUMPH-3 (severe obesity with cardiovascular disease) and TRIUMPH-4 (obesity with knee osteoarthritis), forms the obesity data package Eli Lilly says is now complete for regulatory submission.

Eli Lilly announced topline results on July 23, 2026, in the same press release as TRIUMPH-3. The trial enrolled 1,152 participants and ran for 80 weeks. Participants entered with a mean body weight of 106.4 kg (234.6 lb), a mean BMI of 38.2 kg/m² and a mean A1C of 7.7%.

Trial Design

Study Type

TRIUMPH-2 is a randomized, double-blind, placebo-controlled, multicenter, international trial.

Participant Population

• Adults with obesity or overweight (BMI ≥27 kg/m²) and type 2 diabetes
• Nested obstructive sleep apnea (OSA) basket: a subset of participants with documented OSA
• Final enrollment: 1,152 (earlier program disclosures had projected roughly 1,000)

Dose Selection

Three maintenance doses of once-weekly retatrutide were tested against placebo:

• 4 mg once weekly
• 9 mg once weekly
• 12 mg once weekly

All arms used a stepwise dose-escalation schedule to reach the maintenance dose, as in the rest of the TRIUMPH program.

Endpoints

Primary endpoints:

• Percent change in body weight from baseline at 80 weeks (main population)
• Change in apnea-hypopnea index (AHI) from baseline (OSA basket)

Key secondary endpoints (per the trial registration): proportions of participants reaching ≥5%, ≥10% and ≥15% weight loss; change in A1C; proportions reaching A1C <7.0% and <5.7%; fasting glucose; blood pressure and lipids; liver fat in an imaging substudy; and safety, including hypoglycemia.

Topline Results (July 23, 2026)

Lilly reported the primary weight endpoint and the A1C results under the efficacy estimand, which the release defines as the effect “had all randomized participants remained on study intervention (with possible dose interruptions and modifications) without initiating prohibited weight management treatments (and glycemic rescue therapy for glycemic endpoints only)”. Treatment-regimen (intention-to-treat) figures have not yet been disclosed.

Weight loss at 80 weeks

All three doses met the primary endpoint. Two features of the result stand out. First, the gap between 9 mg and 12 mg was under two percentage points, so most of the benefit of the top dose was already present at 9 mg. Second, the placebo arm lost 4.0%, nearly twice the placebo response in TRIUMPH-1 (2.2%), which is consistent with the more intensive background diabetes management this population receives.

Glycemic control

The A1C effect plateaued at 9 mg. These reductions are smaller than the -1.9 points seen at 12 mg in TRANSCEND-T2D-1, which had a slightly higher baseline (7.9%) and a shorter duration (40 weeks); the two trials also enrolled different populations and used different background therapy, so the figures are not directly comparable. Proportions of participants reaching A1C targets have not yet been released.

Weight loss in people with diabetes: why it is usually smaller

Adults with type 2 diabetes consistently lose less weight on incretin therapies than adults without diabetes. Semaglutide 2.4 mg produced -9.6% in STEP 2 (diabetes) against -14.9% in STEP 1; tirzepatide produced up to -14.7% in SURMOUNT-2 against -22.5% in SURMOUNT-1. Retatrutide follows the same pattern (-20.8% here versus -28.3% in TRIUMPH-1), but the absolute number is the largest yet reported in a Phase 3 obesity trial limited to people with diabetes. This is a cross-trial comparison, not a head-to-head result.

OSA basket

The nested obstructive sleep apnea results (change in AHI) were not included in the topline release. TRIUMPH-1’s nested OSA basket, presented at ADA 2026, showed up to a 60.6% AHI reduction at 12 mg; whether the diabetes population reproduces this is one of the open questions for the full presentation.

Safety Profile

Gastrointestinal adverse events

As in every retatrutide trial, gastrointestinal events were the most common adverse events and were dose-related:

Dysesthesia

Dysesthesia (abnormal skin sensations such as tingling or heightened sensitivity) was reported in 4.5% (4 mg), 5.6% (9 mg) and 7.3% (12 mg) of participants versus 0.7% on placebo. This is the lowest 12 mg dysesthesia rate of any TRIUMPH trial so far: 12.5% in TRIUMPH-1 and 20.9% in TRIUMPH-4. Together with the 2.3–4.5% rates in TRANSCEND-T2D-1, the data now suggest that people with type 2 diabetes experience less dysesthesia than people without it, although the reason is not established. See Retatrutide and Dysesthesia for the full picture across trials.

Treatment discontinuation

Discontinuation because of adverse events was 3.8% at 4 mg, 11.6% at 9 mg and 7.7% at 12 mg, versus 4.9% on placebo. The 9 mg arm discontinued more often than the 12 mg arm, which is unusual and unexplained in the topline release; imbalances of this kind are often clarified when the full data are presented.

Clinical and Regulatory Significance

TRIUMPH-2 was the last obesity trial Lilly needed before filing. In the July 23 release the company stated that it “plans to submit a Biologics License Application (BLA) for retatrutide to FDA in Q1 2027” covering obesity, knee osteoarthritis pain and obstructive sleep apnea, and its August 5 second-quarter report described the clinical data package as “now complete to support global registrations”. A separate diabetes indication would rest on the TRANSCEND program rather than on this trial.

For clinical practice, the trial answers the question that matters most for people who have both obesity and type 2 diabetes: retatrutide produces about 20% weight loss and a 1.5-point A1C reduction in this group at 80 weeks, with a tolerability profile similar to the rest of the program and a lower rate of dysesthesia.

Publication Status

Topline results were announced by Eli Lilly press release on July 23, 2026. Full results will be presented at an EASD-sponsored retatrutide symposium at the EASD 2026 Annual Meeting in Milan on Wednesday, September 30, 2026 (08:30–09:30 CEST). No peer-reviewed publication has appeared yet; this page will be updated when the full data and the OSA basket results are available.

Timeline

• Enrollment start: late 2023
• Topline results: July 23, 2026
• Full presentation: EASD 2026, September 30, 2026
• Regulatory use: part of the BLA Lilly plans to submit in Q1 2027