TRIUMPH-2: Retatrutide for Obesity and Type 2 Diabetes

TRIUMPH-2 is a critical Phase 3 study within the larger retatrutide clinical trials designed specifically for adults who are living with both obesity and Type 2 diabetes.

The medical community is eagerly analyzing TRIUMPH-2: What the Retatrutide Clinical Trials Reveal About Obesity and Type 2 Diabetes as researchers evaluate Eli Lilly’s highly anticipated “triple agonist” molecule.

TRIUMPH-2 Retatrutide for Obesity and Type 2 Diabetes Clinical Trial Over View

• Clinical Trial Registration: NCT05929079
• Top Sponsor of Retatrutide Clinical Trials : Eli Lilly and Company
• Retatrutide Clinical Trial Status: Phase 3, Ongoing as of June 2026
• Primary Readout Expected: Q3–Q4 2026
• Related Trial Published: TRANSCEND-T2D-1 (The Lancet, June 2026).

Why It Matters TRIUMPH-2?

Right now, if someone has both obesity and Type 2 diabetes, treating them is very difficult. Traditional diabetes medicines can help control blood sugar, but they do not help people lose a lot of weight. On the other hand, traditional weight-loss methods do not always fix diabetes.

This is why the new retatrutide clinical trials are such a big deal. For the first time, one single drug is doing two massive jobs at the exact same time:

• Surgical-level weight loss: It helps people lose a massive amount of weight, almost as much as having a stomach surgery.
• Excellent blood sugar control: It lowers blood sugar levels down to a safe, healthy range.

By fixing both problems at once, this treatment can prevent major health disasters like heart attacks, strokes, and severe sleep apnea. If the testing continues to go well, it will change how doctors treat diabetes forever and help millions of people live healthier, longer lives.

KEY TAKEAWAYS

• Pivotal Phase 3 Trial: TRIUMPH-2 represents Eli Lilly’s crucial Phase 3 retatrutide clinical trials focusing on adults living with both obesity and Type 2 diabetes, a critically underserved patient population.
• Timeline to Watch: While final data from these specific retatrutide clinical trials are anticipated in late 2026, existing Phase 2 foundation and the TRANSCEND-T2D-1 study offer massive promise.
• Near-Surgical Results: Early data suggests retatrutide may be the first therapeutic agent capable of delivering near-surgical-level weight loss alongside powerful, simultaneous glycemic control.
• A New Standard of Care: By successfully conquering a dual challenge that has eluded previous anti-obesity and diabetes medications, these ongoing retatrutide clinical trials could redefine treatment for tens of millions of people worldwide.

What Is TRIUMPH-2? The Core Idea

For the majority of adults living with obesity, the condition does not travel alone. Type 2 diabetes (T2D) is one of its most common companions, and also one of its most complicated. The two diseases are deeply connected at the biological level: excess fat tissue drives insulin resistance, and insulin resistance accelerates weight gain, creating a self-reinforcing cycle that is notoriously difficult to interrupt.

What makes this population so challenging to treat is a well-documented clinical paradox. Most anti-obesity drugs, particularly GLP-1 receptor agonists, produce meaningfully less weight loss in people with T2D than in people without it. Semaglutide (Wegovy), for example, produced approximately 15% weight loss in its pivotal obesity trial (STEP-1) but only around 10% in its T2D-focused counterpart. Tirzepatide (Mounjaro/Zepbound) narrowed that gap considerably, achieving around 14–16% in the T2D population versus 22.5% in non-diabetic patients. But the gap persisted.

TRIUMPH-2 was designed to determine whether retatrutide’s triple-receptor mechanism, targeting GIP, GLP-1, and glucagon simultaneously, can close that gap entirely, or at least reduce it to the point of clinical insignificance. The trial asks a question with enormous real-world stakes: can a single drug treat both the weight and the diabetes at the same time? at a level of effectiveness that genuinely changes the disease trajectory?

The answer to that question carries implications not just for retatrutide’s regulatory approval, but for how medicine thinks about treating obesity and diabetes as a combined, inseparable condition, rather than two diseases managed with two separate drug classes by two separate specialists.

How the Retatrutide Clinical Trials Started and What It Set Out to Do

The Phase 2 Foundation in Type 2 Diabetes

TRIUMPH-2 was built on two layers of Phase 2 evidence, both published in 2023.

The first was the landmark obesity Phase 2 trial published in the New England Journal of Medicine by Jastreboff et al., which established retatrutide’s extraordinary weight-loss profile in non-diabetic adults, up to 24.2% at 48 weeks. But that trial excluded people with T2D. A separate, parallel Phase 2 trial specifically enrolled 281 adults with Type 2 diabetes (mean HbA1c 8.3%, mean BMI 35.0 kg/m²), published simultaneously in The Lancet by Rosenstock et al. That trial tested retatrutide at doses from 0.5 mg through 12 mg over 36 weeks, with dulaglutide (a standard GLP-1 receptor agonist) as an active comparator.

The T2D Phase 2 results were striking on both dimensions. HbA1c dropped by 1.3% to 2.0% across the 4–12 mg dose groups, significantly greater than both placebo and dulaglutide at the higher doses.

Eighty-two percent of participants in the higher-dose groups achieved an HbA1c of 6.5% or below, a threshold that defines well-controlled diabetes. At the same time, weight loss in the T2D population was substantial: the 12 mg group lost meaningful body weight alongside their glycemic improvements, accompanied by a striking 82% reduction in hepatic steatosis (liver fat). These Phase 2 T2D findings established retatrutide as the first incretin-class drug to produce what scientists called “dual dominance”, simultaneously leading in both glycemic control and weight reduction in a T2D population.

That evidence base provided the justification to advance TRIUMPH-2 into large-scale Phase 3 testing.

Trial Design

TRIUMPH-2 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial. It runs for approximately 80 weeks (89 weeks total including screening and follow-up), with the same dose structure used across the TRIUMPH program.

Participants are randomized 1:1:1:1 to four groups:

• Retatrutide 4 mg once weekly
• Retatrutide 9 mg once weekly
• Retatrutide 12 mg once weekly
• Placebo

As in TRIUMPH-1, all participants begin at 2 mg once weekly and escalate the dose in steps every four weeks until reaching their assigned target dose. This gradual titration protocol is designed to minimize gastrointestinal side effects, the most common adverse events associated with incretin-based therapies.

Who Was Enrolled in TRIUMPH-2?

TRIUMPH-2 enrolled approximately 1,000 adults with Type 2 diabetes who also have obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity. Unlike TRANSCEND-T2D-1, which enrolled medication-naïve early-diabetes patients, TRIUMPH-2 was designed to reflect a broader and more representative T2D population, including participants on existing glucose-lowering medications.

The Nested OSA Basket Protocol of TRIUMPH-2 Retatrutide Clinical Trial

Like TRIUMPH-1, TRIUMPH-2 includes a nested basket trial for obstructive sleep apnea (OSA) within its master protocol. A subset of participants with moderate-to-severe OSA underwent dedicated polysomnography assessments, with the Apnea-Hypopnea Index (AHI) as the primary endpoint for the OSA sub-protocol. This design mirrors the approach used in TRIUMPH-1 and reflects the high prevalence of sleep apnea in people with both obesity and T2D.

Dual Primary Endpoints of Retatrutide Clinical Trial TRIUMPH-2

TRIUMPH-2 is unique within the TRIUMPH program in having two co-primary objectives:

1. Percent change in body weight at 80 weeks (the obesity endpoint)
2. Reduction in HbA1c from baseline (the glycemic control endpoint)

This dual structure reflects the clinical reality of the target population, and the regulatory reality that Eli Lilly intends to pursue a combined obesity-plus-diabetes indication label for retatrutide, which would require demonstrating efficacy on both measures in the same trial.

What TRIUMPH-2 Brings to the Table?

The clinical challenge TRIUMPH-2 addresses is not just one of drug efficacy. It is a challenge of disease framing.

For decades, obesity and Type 2 diabetes have been treated as separate conditions sitting in separate medical silos. A patient with both conditions might see an endocrinologist for their HbA1c and a separate specialist, or no specialist at all, for their weight. The drugs prescribed for each condition were developed independently, approved independently, and often worked against each other. Many diabetes medications (including insulin and sulfonylureas) cause weight gain, undermining the very metabolic improvements they are intended to produce.

TRIUMPH-2 is built on the premise that this siloed model is biologically wrong and clinically counterproductive. Obesity and T2D share the same root pathophysiology: disrupted incretin signaling, impaired insulin sensitivity, and dysregulated energy homeostasis. A drug that targets all three relevant hormone receptors simultaneously, GIP, GLP-1, and glucagon, is designed to address the shared mechanism, not just manage individual symptoms.

Three specific things make TRIUMPH-2 clinically novel:

Treating the Harder Population

The T2D population is consistently harder to treat with weight-loss drugs than non-diabetic populations. If retatrutide produces results in TRIUMPH-2 that are meaningfully close to those seen in TRIUMPH-1, it would demonstrate that triple agonism substantially overcomes the “T2D blunting effect” seen with prior drug classes, a breakthrough that would shift prescribing patterns fundamentally.

The “dual dominance” Concept at Phase 3 Scale

Phase 2 showed retatrutide leading simultaneously on weight loss and glycemic control versus an active GLP-1 comparator, a combination no prior drug had achieved. TRIUMPH-2 tests whether that dual dominance holds at large scale, with a more diverse and complex patient population.

The OSA-nested design in a T2D Population

Sleep apnea is disproportionately common in people with both obesity and T2D. By including an OSA basket within TRIUMPH-2 specifically, Lilly is generating the first large-scale data on whether aggressive metabolic treatment in this high-risk group can produce meaningful apnea reduction, a question with major implications for cardiovascular risk management in diabetic patients.

T2D Population stands for Type 2 Diabetes Population.

Publications and Related Data

TRIUMPH-2 final results had not been announced as of June 2026. The readout is expected in Q3–Q4 2026, with data presentations anticipated at major endocrinology conferences in late 2026 and peer-reviewed publication to follow.

However, two closely related publications provide essential scientific context:

Phase 2 Type 2 Diabetes Trial (The Lancet, 2023):

Rosenstock J, et al. Retatrutide, a GIP, GLP-1, and Glucagon Receptor Agonist, for People with Type 2 Diabetes. The Lancet. 2023. doi:10.1016/S0140-6736(23)01053-X

This was the foundational Phase 2 evidence establishing retatrutide’s dual efficacy in HbA1c and body weight in a T2D population, directly informing TRIUMPH-2’s design.

TRANSCEND-T2D-1 Phase 3 Trial (The Lancet, June 2026):

Bajaj H, Rosenstock J, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. The Lancet. June 2026. doi:10.1016/S0140-6736(26)00967-0

TRANSCEND-T2D-1 is a separate trial that tests early-stage Type 2 Diabetes patients who are not yet on medication.

However, its Phase 3 data was recently published in The Lancet during the ADA 2026 Scientific Sessions.

This publication provides the very first peer-reviewed Phase 3 data on how retatrutide works in a Type 2 Diabetes population.

Because of this, it is currently the closest scientific data we have to compare against what TRIUMPH-2 is expected to prove.

TRIUMPH Program Design Paper:

Giblin K, Kaplan LM, Somers VK, Le Roux CW, Hunter DJ, Wu Q, Lalonde A, Ahmad N, Bethel MA. Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational retatrutide clinical trials. Diabetes, Obesity and Metabolism. 2026 Jan;28(1):83–93. doi:10.1111/dom.70209

The Scientists Behind the TRIUMPH-2 Clinical Trial of Retatrutide

Dr. Julio Rosenstock, MD

Dr. Julio Rosenstock is a Key Investigator. He is the Director of the Dallas Diabetes Research Center at Medical City Dallas. He also works as a Clinical Professor of Medicine at the University of Texas Southwestern Medical Center.

Dr. Rosenstock earned his MD from the University of Costa Rica. Later, he completed medical fellowships at the Royal Postgraduate Medical School at Hammersmith Hospital in London. He completed another fellowship at UT Southwestern.

Over his 40-year career, Dr. Rosenstock has written or helped write more than 516 medical publications. He has also participated in hundreds of clinical trials. Recently, he played a leading role in both the Phase 2 Type 2 Diabetes retatrutide clinical trials and the TRANSCEND-T2D-1 Phase 3 publication. Today, he is recognized as one of the most productive diabetes clinical trial researchers in the world.

Dr. Ania M. Jastreboff, MD, PhD

Program Investigator Founding Director of the Yale Obesity Research Center (Y-Weight) and lead investigator for TRIUMPH-1. Dr. Jastreboff’s involvement extends across the TRIUMPH program as a whole. Her expertise bridges both the obesity and metabolic medicine domains, making her a key scientific voice for how TRIUMPH-2 results will be interpreted in the context of combined obesity-T2D management.

Dr. Kathryn Giblin, MD

Senior Director, Clinical Development, Eli Lilly Corresponding author on the TRIUMPH program design paper and the operational lead for trial design and protocol coordination across all TRIUMPH arms, including TRIUMPH-2.

Dr. Lee M. Kaplan, MD, PhD

Steering Committee Member Professor of Medicine and Chief of Obesity Medicine at the Geisel School of Medicine at Dartmouth. Dr. Kaplan contributes expertise in the gastrointestinal mechanisms underlying both obesity treatment response and metabolic surgery, directly relevant to the combined T2D and obesity population targeted by TRIUMPH-2.

Prof. Carel W. le Roux, MBChB, PhD

Steering Committee Member Director of the Metabolic Medicine Group at University College Dublin. His translational research on gut-brain signaling and the physiology of bariatric surgery informs the understanding of how retatrutide’s triple mechanism affects the metabolic dysfunction driving both obesity and T2D.

Dr. Tamer Coskun, MD, PhD

Inventor, Retatrutide Vice President-Medical at Eli Lilly. The principal inventor of retatrutide and the scientist who established the triple GIP/GLP-1/glucagon agonism concept that defines the drug’s mechanism. His discovery work, published in Cell Metabolism in 2022, provides the mechanistic rationale for why a triple agonist is expected to produce superior outcomes in a T2D population compared to single or dual agonists.

The Results (TRANSCEND-T2D-1 as Current Best Evidence)

The full results for TRIUMPH-2 are still pending as of June 2026. Because of this, the data below comes from a different study called TRANSCEND-T2D-1. This Phase 3 trial looked at retatrutide’s effects on Type 2 diabetes. Its results were first announced on March 19, 2026, and were later published in The Lancet during the ADA 2026 Scientific Sessions.

These two studies are distinct. The TRANSCEND-T2D-1 study enrolled early-stage Type 2 diabetes patients who were not yet taking medication, which is different from the broader patient group in TRIUMPH-2. However, TRANSCEND-T2D-1 still provides the most directly relevant published Phase 3 data on how the drug performs in a Type 2 diabetes population. Until the TRIUMPH-2 results are officially reported, this study serves as our best available scientific reference point.

Trial Details

• Participants: 537 adults with Type 2 diabetes (HbA1c 7.0–9.5%, mean baseline 7.9%; mean BMI ≥ 23 kg/m²; mean T2D duration 2.5 years)
• Design: 40-week, randomized, double-blind, placebo-controlled (1:1:1:1 allocation)
• Sites: 48 medical research centers and hospitals across India, Mexico, and the USA
• Population profile: Medication-naïve (not on glucose-lowering drugs for at least 90 days prior)

Primary Endpoint: HbA1c Reduction at 40 Weeks

Group	Mean HbA1c Reduction
Retatrutide 4 mg	−1.69%
Retatrutide 9 mg	−1.86%
Retatrutide 12 mg	−1.94% (from baseline 7.9%)
Placebo	−0.81%

• 90% of participants on retatrutide reached the ADA’s general HbA1c target of below 7.0%
• 85% achieved 6.5% or below, a threshold associated with well-controlled diabetes
• No weight loss plateau was observed through week 40 on any active dose

Secondary Endpoint: Weight Loss at 40 Weeks

Group	Mean Weight Loss
Retatrutide 4 mg	−11.5%
Retatrutide 9 mg	−13.9%
Retatrutide 12 mg	−16.8% (approximately 36.6 lbs / 16.6 kg)
Placebo	−2.6%

Cardiometabolic Secondary Endpoints (12 mg vs. baseline)

• Triglycerides: reduced by up to 39.6%
• Non-HDL cholesterol: reduced by up to 19.8%
• Systolic blood pressure: reduced by 6.4 mmHg
• Waist circumference: reduced by 4.9 inches (12.4 cm)

Safety Profile

The side effects in this study matched what doctors usually see with similar weight-loss drugs. The most common issues affected the stomach. For patients taking the highest dose (12 mg), up to 26.5% reported nausea, up to 22.8% experienced diarrhea, and up to 17.6% dealt with vomiting.

Very few people decided to quit the study because of these side effects. Only 2.2% of patients on the 4 mg dose stopped taking the medicine. That number was 4.5% for the 9 mg dose, and 5.1% for the highest 12 mg dose. Meanwhile, nobody in the dummy pill (placebo) group dropped out. Overall, this is one of the best and most favorable safety profiles seen in any retatrutide clinical trials so far.

What the Results of TRIUMPH-2 Clinical Trial Mean?

The TRANSCEND-T2D-1 data—and the larger TRIUMPH-2 framework designed to validate it—offers a meaningful advance over any previous treatment for people living with both Type 2 diabetes and obesity.

The dual achievement is real

A drug that simultaneously reduces HbA1c by up to 2.0% and body weight by up to 16.8% in a 40-week trial, with 90% of patients reaching an HbA1c below 7.0% and no plateau in weight loss, accomplishes in a single weekly injection what previously required combining a glucose-lowering agent with a separate weight management strategy, typically with inferior results on both dimensions.

The T2D blunting effect is partially overcome

Historically, the same drug produces less weight loss in people with T2D than in people without it. At 16.8%, retatrutide’s T2D weight loss result is meaningfully higher than what semaglutide or tirzepatide achieve in comparable T2D populations, confirming that the addition of glucagon receptor agonism provides benefits that specifically help overcome the metabolic resistance driving attenuated weight loss in diabetes.

Disease trajectory, not just symptom management

The study’s authors concluded that retatrutide could offer a first-line treatment for early Type 2 diabetes, not just as a drug to manage an established chronic disease, but as an intervention that addresses its biological drivers early enough to potentially alter its course.

TRIUMPH-2 will extend this story

Where TRANSCEND-T2D-1 enrolled medication-naïve patients with early-stage T2D over 40 weeks, TRIUMPH-2 follows a larger, longer-duration, more complex population over 80 weeks, including patients already on glucose-lowering medications. Its results will determine whether the dual efficacy signal holds across a broader and harder-to-treat T2D population, and whether the OSA basket data confirm the systemic benefits of treating obesity-plus-T2D with triple agonism.

Frequently Asked Questions About TRIUMPH-2, Retatrutide Clinical Trial (FAQ)

What are the retatrutide clinical trials?

The retatrutide clinical trials are a global, multi-phase Phase 3 clinical research initiative spearheaded by Eli Lilly to evaluate the safety and effectiveness of retatrutide, an investigational “triple agonist” medication targeting GLP-1, GIP, and glucagon receptors to simultaneously suppress appetite and boost energy expenditure.

Eli Lilly broadly divides this extensive testing framework into two main programs: TRIUMPH and TRANSCEND. The TRIUMPH program examines weight management and related health problems like obstructive sleep apnea and heart risks. Meanwhile, the TRANSCEND program focuses directly on blood sugar control and weight loss for patients with Type 2 diabetes.

Early data has yielded historic result, such as a 28.3% average weight loss in general obesity groups over 80 weeks in the TRIUMPH-1 trial; while researchers monitor common gastrointestinal side effects during dose escalation.

Because these trials are wrapping up throughout 2026, Eli Lilly is utilizing the full data package to prepare for a planned regulatory New Drug Application (NDA) submission, paving the way for potential FDA approval by 2027.

What is TRIUMPH-2 testing?

TRIUMPH-2 is evaluating retatrutide, a first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist, in approximately 1,000 adults who have both Type 2 diabetes and obesity or overweight. It is a Phase 3, randomized, double-blind, placebo-controlled trial lasting approximately 80 weeks, with two co-primary endpoints: percent change in body weight and reduction in HbA1c.

How is TRIUMPH-2 different from TRIUMPH-1?

TRIUMPH-1 enrolled adults with obesity but without Type 2 diabetes. TRIUMPH-2 enrolls adults who have both conditions. This distinction matters clinically because T2D consistently makes weight loss harder to achieve with drug therapy. TRIUMPH-2 also adds HbA1c as a co-primary endpoint alongside body weight.

What is TRANSCEND-T2D-1 and how does it relate to TRIUMPH-2?

TRANSCEND-T2D-1 is a separate but related Phase 3 trial of retatrutide in Type 2 diabetes, published in The Lancet in June 2026. It enrolled medication-naïve early-T2D patients over 40 weeks and demonstrated up to 2.0% HbA1c reduction and 16.8% weight loss at 12 mg. TRIUMPH-2 will test a larger, more complex T2D-with-obesity population over 80 weeks, providing a more comprehensive and regulatory-relevant dataset for the combined indication.

When will TRIUMPH-2 results be announced?

Eli Lilly has indicated that TRIUMPH-2 results are expected in Q3–Q4 2026. As of June 2026, results have not yet been announced.

Does retatrutide produce less weight loss in people with diabetes?

Based on TRANSCEND-T2D-1, retatrutide produced 16.8% mean weight loss at 40 weeks in a T2D population, lower than the 28.3% seen in TRIUMPH-1 (non-diabetic, 80 weeks), but notably higher than what semaglutide and tirzepatide produce in their respective T2D populations. The longer duration of TRIUMPH-2 (80 vs. 40 weeks) is expected to produce higher final weight loss figures.

What side effects are expected?

The most common side effects are gastrointestinal, primarily nausea, diarrhea, and vomiting, consistent with the broader GLP-1 drug class. In TRANSCEND-T2D-1, the T2D population showed notably better tolerability than the general obesity populations in TRIUMPH-1 and TRIUMPH-4, with discontinuation due to adverse events of just 5.1% at the highest dose.

Who are the lead scientists on TRIUMPH-2?

The trial is led within Eli Lilly’s clinical development team, with Dr. Kathryn Giblin as program design lead. External investigators include Dr. Julio Rosenstock (Dallas Diabetes Research Center), Dr. Ania Jastreboff (Yale), Dr. Lee Kaplan (Dartmouth), and Prof. Carel le Roux (University College Dublin). Dr. Tamer Coskun, the inventor of retatrutide, provides the foundational discovery science underpinning the entire program.

What happens after TRIUMPH-2?

If TRIUMPH-2 meets its endpoints, it will support a combined obesity-plus-diabetes label for retatrutide, potentially the broadest and most clinically impactful labeling ever sought for a single anti-obesity drug. An NDA submission to the FDA is targeted for Q4 2026, with approval not anticipated before 2027.