---
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| **The First Phase 3 Obesity Study of Retatrutide, a GIP, GLP-1, and Glucagon Receptor Agonist, in People with Obesity\ |
| (TRIUMPH-1)** |
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| ADA Scientific Sessions |
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| June 6, 2026 |
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| Authors: Ania M. Jastreboff, MD, PhD |
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| Harvey & Kate Cushing Professor, Yale University School of Medicine |
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| Internal Medicine, Endocrinology & Metabolism |
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| Pediatrics, Pediatric Endocrinology |
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| Director, Yale Obesity Research Center (Y-Weight) |
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| ## **Disclosures** |
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| **RESEARCH SUPPORT:** |
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| - Amgen |
| - Boehringer Ingelheim |
| - Eli Lilly |
| - NIH/NIDDK |
| - Novo Nordisk |
| - Rhythm Pharmaceuticals |
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| **OPTIONS/SHARES:** |
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| - Intellihealth |
| - Metsera |
| - State 4 Tx – academic co-founder |
| - Syntis Bio |
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| **SCIENTIFIC ADVISORY BOARD:** |
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| - Amgen |
| - AstraZeneca |
| - Boehringer Ingelheim |
| - Biohaven |
| - Eli Lilly |
| - i2o |
| - Kailera |
| - Metsera |
| - Novo Nordisk |
| - Pfizer |
| - Regeneron |
| - Roche/Genentech |
| - Scholar Rock |
| - Structure Therapeutics |
| - Viking |
| - Wave |
| - WW (WeightWatchers) |
| - Zealand Pharmaceuticals |
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| ## **TRIUMPH-1** |
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| ## **Study Design and Participant Disposition** |
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| #### **TRIUMPH-1: Retatrutide Phase 3 Obesity Trial** |
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| #### Study Overview |
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| ![Study Overview][image0] |
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| OSA=obstructive sleep apnea; OA=osteoarthritis. |
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| #### **TRIUMPH-1: Retatrutide Phase 3 Obesity Trial** |
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| #### Key Inclusion and Exclusion |
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| AHI=Apnea-Hypopnea Index; OA=osteoarthritis; OSA=obstructive sleep apnea; PAP=positive airway pressure; |
| PSG=polysomnography; WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index. |
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| #### Study Design |
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| ![Randomized, double-blind, Phase 3 trial of weekly retatrutide vs. placebo][image2] |
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| **Randomized, double-blind, Phase 3 trial of weekly retatrutide vs. placebo** |
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| in participants with obesity, including subsets of participants with OSA or knee OA |
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| Giblin K, et al. Diabetes Obes Metab. 2026; https\://clinicaltrials.gov/study |
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| BMI=body mass index; MTD=maximum tolerated dose; OA=osteoarthritis; OSA=obstructive sleep apnea; PBO=placebo; |
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| RETA=retatrutide |
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| #### Primary and Key Secondary Endpoints |
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| ![Primary and Key Secondary Endpoints][image3] |
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| **TRIUMPH-1 Overall Study** |
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| HDL=high-density lipoprotein; hsCRP=high-sensitivity C-reactive protein. |
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| ## **TRIUMPH-1** |
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| ## **Participant Characteristics** |
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| **Baseline Demographics** |
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| - ## OA basket: Participants were older and included more female participants. |
| - ## OSA basket: More Hispanic participants and more male participants. |
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| OA=osteoarthritis; OSA=obstructive sleep apnea. |
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| Anthropometric Measures |
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| ## Average baseline BMI = class 3 obesity (BMI ≥40 kg/m2) |
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| Data are shown as mean (SD) unless stated otherwise\ |
| BMI=body mass index; PBO=placebo; RETA=retatrutide; SD=standard deviation |
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| ## PBO: 75% completed the study, with \~64% completing on treatment
RETA: \~89%-91% completed the study, with \~75%-87% completing on treatment |
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| PBO=placebo; RETA=retatrutide |
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| ## **TRIUMPH-1** |
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| ## **Primary and Secondary Outcomes** |
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| ![Weight Reduction Over 80 Weeks With Retatrutide TRIUMPH-1 Primary Outcome][image7] |
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| **Weight Reduction Over 80 Weeks With Retatrutide** |
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| TRIUMPH-1 Primary Outcome |
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| - #### With RETA 4 mg, a dose which had only one up-titration step, weight reduction was an average of 19% at 80 weeks |
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| * #### With RETA 12 mg, weight reduction was an average of 28.3% at 80 weeks |
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| All groups p<0.001 vs. PBO.PBO=placebo; RETA=retatrutide; EE=Efficacy Estimand; TRE=Treatment Regimen Estimand.All |
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| **Weight Reduction Over 104 Weeks With Retatrutide** |
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| TRIUMPH-1 Extension |
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| All Addendum Participants |
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| *N=532 total* |
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| ## Participants in the extension lost up to an average of 30% of their initial weight at 104 weeks |
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| All groupp<0.001 vs. PBO.BMI=body mass index; EE=Efficacy Estimand; MTD=maximum tolerated dose; PBO=placebo; |
| RETA=retatrutide; TRE=Treatment Regimen Estimand. |
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| *Efficacy Estimand* |
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| ## Clinically meaningful weight reduction in nearly all participants treated with RETA,including reaching higher weight reduction thresholds of ≥30% and ≥35% |
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| \*\*\*p<0.001 vs. PBO.PBO=placebo; RETA=retatrutide. |
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| *Efficacy Estimand* |
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| The efficacy observed with RETA potentially allows for a treat-to-target approach rather than relative change in |
| weight approach, though data are needed to demonstrate health benefits with targets |
+-----------------------------------------------------------------------------------------------------------------------+
| \*\*\*p<0.001 vs. PBO.BMI=body mass index; PBO=placebo; RETA=retatrutide; WtHR=waist-to-height ratio. |
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+-----------------------------------------------------------------------------------------------------------------------+
| ## TRIUMPH-1 |
| |
| ## Primary Outcomes of the Knee OA and OSA Baskets |
+-----------------------------------------------------------------------------------------------------------------------+
| |
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| ![TRIUMPH-1- OA Basket Knee Osteoarthritis N=574 total Absolute Change in WOMAC Pain Subscale Score][image11] |
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| |
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| |
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| **TRIUMPH-1- OA Basket** |
| |
| Knee Osteoarthritis |
| |
| *N=574 total* |
| |
| Absolute Change in **WOMAC Pain Subscale Score** |
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| RETA resulted in a WOMAC pain score reduction more than the clinically significant threshold of 4 points |
| |
| Which translates to up to more than a 70% decrease in pain with RETA |
+-----------------------------------------------------------------------------------------------------------------------+
| \*\*\*p<0.001 vs. PBO.BMI=body mass index; OA=osteoarthritis; PBO=placebo; RETA=retatrutide; WOMAC=Western Ontario |
| and McMaster Universities Osteoarthritis Index. |
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| |
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| ![TRIUMPH-1 OSA Basket Obstructive Sleep Apnea N=243 total Absolute Change in Apnea Hypopnea Index (AHI)][image11] |
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| **TRIUMPH-1 OSA Basket** |
| |
| Obstructive Sleep Apnea |
| |
| *N=243 total* |
| |
| Absolute Change in **Apnea Hypopnea Index (AHI)** |
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| ## RETA resulted in an AHI reduction more than the clinically significant threshold of 15 events per hr |
| |
| ## Which translates to up to more than a 60% decrease in AHI with RETA |
+-----------------------------------------------------------------------------------------------------------------------+
| \*p<0.05, \*\*p<0.01, \*\*\*p<0.001 vs PBO. |
| |
| AHI=Apnea-Hypopnea Index; BMI=body mass index; OSA=obstructive sleep apnea; PBO=placebo; RETA=retatrutide. |
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+-----------------------------------------------------------------------------------------------------------------------+
| ## **TRIUMPH-1** |
| |
| ## **Cardiometabolic Measures and Patient-Reported Outcomes** |
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| ![Cardiometabolic Measures at 80 weeks with Retatrutide][image12] |
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| Cardiometabolic Measures at 80 weeks with Retatrutide |
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| *Efficacy Estimand* |
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| ## Greater improvements in blood pressure, lipids, hsCRP, and glycemia in all RETA arms than with PBO |
+-----------------------------------------------------------------------------------------------------------------------+
| \*\*\*p<0.001 vs PBO\ |
| BP=blood pressure; hsCRP=high-sensitivity C-reactive protein; LDL-C=low-density lipoprotein cholesterol; PBO=placebo; |
| RETA=retatrutide; SBP=systolic blood pressure;TG=triglycerides. |
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| ![Patient-Reported Outcomes at Week 80 with Retatrutide Impact of Weight on Quality of Life (IWQOL)][image13] |
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| *Efficacy Estimand* |
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| ## Greater improvements in physical function and psychosocial quality of life measures with RETA than with PBO |
+-----------------------------------------------------------------------------------------------------------------------+
| \*\*\*p<0.001 vs. PBO. IWQOL-Lite-CT=Impact of Weight on Quality of Life–Lite Clinical Trials; PBO=placebo; |
| RETA=retatrutide. |
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| ## **TRIUMPH-1** |
| |
| ## **Safety and Tolerability** |
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| - ## Treatment-emergent adverse events were reported in 80.7% of the participants in the PBO group and 87%-89.2% of participants in the RETA groups |
| - ## Serious adverse events were reported in 5.5% of the participants in the PBO group and 7.7%-10.5% of participants in the RETA groups |
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| aAll deaths were adjudicated by an external committee of physicians as to whether the death was a cardiovascular-related death or not. |
| AE=adverse event; PBO=placebo; RETA=retatrutide. |
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| ## UTIs were reported in 6.8%-8.1% of participants in RETA arms, and 4.8% with PBO, mostly mild to moderate in severity, resolved on treatment, and did not lead to discontinuation; 92% were in female participants |
+----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------+
| AE=adverse event; COVID-19=coronavirus disease 2019; PBO=placebo; RETA=retatrutide UTI=urinary tract infection. |
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| - ## Discontinuation due to adverse event occurred in 4%-11% of participants who received RETA and 5% of those who received PBO |
| - ## Gastrointestinal adverse events were the most common reason for treatment discontinuation; 2.2-4.6% in the RETA arms and 1.2% in the PBO arm |
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| AE=adverse event; PBO=placebo; PT=preferred term; RETA=retatrutide. |
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| ## Most prevalent AESI were dysesthesia, injection site reactions, GI AEs, and reported hypotension, with the latter being more common in participants taking anti-hypertensive medications |
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| AESI=adverse event of special interest; GI=gastrointestinal; MACE=major adverse cardiovascular event; PBO=placebo; RETA=retatrutide. |
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| ## **TRIUMPH-1: Summary** |
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| #### TRIUMPH-1: Summary of Phase 3 Obesity Trial With Retatrutide |
| |
| ###### **Retatrutide**, a **once-weekly triple hormone receptor agonist**, was generally well-tolerated and provided substantial reductions in weight as well as clinically meaningful improvements in health outcomes for patients with obesity, OSA, and knee OA |
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| **Thank You** |
+-----------------------------------------------------------------------------------------------------------------------+
| We express our appreciation to the participants of the study, and the investigators and study coordinators who cared |
| for them and the study sponsor, Eli Lilly. |
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| title | The First Phase 3 Obesity Study of Retatrutide, a GIP, GLP-1, and Glucagon Receptor Agonist, in People with Obesity (TRIUMPH-1) |
+--------------------------+------------------------------------------------------------------------------------------------------------------------------------+
| published-time | 2026-06-16T17:30:47.657Z |
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| | "https\://lilly.com/hcp/congresses/ada-2026/dv039292-triumph-1#webpage", "name": "TRIUMPH-1 Results Presentation — ADA 2026", |
| | "url": "https\://lilly.com/hcp/congresses/ada-2026/dv039292-triumph-1", "description": "Official Eli Lilly HCP congress |
| | presentation of TRIUMPH-1 Phase 3 results, presented at the American Diabetes Association Scientific Sessions 2026 by Ania M. |
| | Jastreboff, MD, PhD", "keywords": "retatrutide, TRIUMPH-1, obesity, weight loss, triple hormone receptor agonist, GIP receptor |
| | agonist, GLP-1 receptor agonist, glucagon receptor agonist, once-weekly injection, body weight reduction, 25% weight loss, 30% |
| | weight loss, obstructive sleep apnea, knee osteoarthritis, cardiometabolic outcomes, blood pressure reduction, triglyceride |
| | reduction, prediabetes normoglycemia, quality of life IWQOL, apnea-hypopnea index, Eli Lilly, phase 3 clinical trial, ADA 2026, |
| | randomized controlled trial", "abstract": "PRIMARY OUTCOMES (Week 80): Percent change in body weight — Efficacy estimand: PBO |
| | −2.2%, RETA 4 mg −19.0%, RETA 9 mg −25.9%, RETA 12 mg −25.9%. Proportion achieving ≥5% weight loss: PBO 34.3%, RETA 4 mg 91.3%, |
| | RETA 9 mg 97.0%, RETA 12 mg 97.3% (p<0.001). Weight loss thresholds (RETA 12 mg vs PBO): ≥10% 93.2% vs 15.9%; ≥15% 87.5% vs 7.6%; |
| | ≥20% 76.2% vs 4.1%; ≥25% 62.5% vs 2.2%; ≥30% 45.3% vs 0.5%; ≥35% 27.2% vs 0.3%. BMI <30 achieved: RETA 12 mg 65.3% vs PBO 7.6%. |
| | EXTENSION (Week 104, RETA 12 mg/MTD): −30.3% body weight (efficacy estimand). KEY SECONDARY OUTCOMES (Week 80): SBP change: RETA |
| | 12 mg −12.3 mmHg vs PBO −1.1 mmHg (p<0.001). Triglycerides: RETA 12 mg −41.0% vs PBO −5.0% (p<0.001). LDL-C: RETA 12 mg −19.6% vs |
| | PBO −2.1% (p<0.001). hsCRP: RETA 12 mg −63.8% vs PBO −23.5% (p<0.001). Prediabetes reversion to normoglycemia: RETA 12 mg 95.7% vs |
| | PBO 48.7% (p<0.001). IWQOL physical function change: RETA 12 mg \+29.3 vs PBO \+11.9 (p<0.001). OSA BASKET (N=243): AHI change — |
| | RETA 9 mg −36.1, RETA 12 mg −33.8 vs PBO −11.1 (p<0.001). OA BASKET (N=574): Greater knee pain improvement in all RETA arms vs |
| | PBO. SAFETY: Most common AEs were GI (nausea, diarrhea, constipation, vomiting), predominantly mild-to-moderate during dose |
| | escalation. Discontinuation due to AEs: PBO 4.9%, RETA 4 mg 4.1%, RETA 9 mg 6.9%, RETA 12 mg 11.3%.", "author": { "@type": |
| | "Person", "@id": "https\://lilly.com/hcp/congresses/ada-2026/dv039292-triumph-1#author-jastreboff", "name": "Ania M. |
| | Jastreboff", "honorificSuffix": "MD, PhD", "affiliation": { "@type": "EducationalOrganization", "@id": |
| | "https\://medicine.yale.edu", "name": "Yale University School of Medicine", "department": "Internal Medicine, |
| | Endocrinology & Metabolism; Pediatric Endocrinology" }, "jobTitle": "Harvey & Kate Cushing Professor; Director, Yale |
| | Obesity Research Center (Y-Weight)" }, "mainEntity": { "@type": "MedicalStudy", "@id": |
| | "https\://lilly.com/hcp/congresses/ada-2026/dv039292-triumph-1", "name": "TRIUMPH-1: Phase 3 Obesity Trial of Retatrutide", |
| | "alternateName": \[ "TRIUMPH-1", "Retatrutide Phase 3 Obesity Study" ], "description": "A randomized, |
| | double-blind, placebo-controlled, parallel-group, Phase 3 trial evaluating once-weekly subcutaneous retatrutide (4 mg, 9 mg, 12 |
| | mg) versus placebo in 2339 adults with obesity (mean baseline BMI 40 kg/m²; mean body weight 248.5 lbs / 112.7 kg), including |
| | disease-specific baskets for obstructive sleep apnea (OSA, N=243) and knee osteoarthritis (OA, N=574). Randomized 1:1:1:1 to PBO, |
| | RETA 4 mg, RETA 9 mg, RETA 12 mg QW. Dose escalation period 0–16 weeks (starting dose 2 mg, titrated to 4 mg, 6 mg, then 9 mg or |
| | 12 mg). Treatment period with visits Q4W through Week 80. Extension study through Week 104 (first 532 eligible completers, |
| | re-randomized to RETA MTD). Post-treatment follow-up through Week 108. All participants received individualized lifestyle |
| | counselling. Study population: N=2339 randomized (PBO N=587, RETA 4 mg N=584, RETA 9 mg N=584, RETA 12 mg N=584). Mean baseline |
| | BMI 40.0 kg/m²; mean body weight 112.7 kg / 248.5 lbs. BMI categories: Class 1 (30–<35) 20.6%, Class 2 (35–<40) 35.2%, Class 3 |
| | (≥40) 42.1%. Retatrutide is a once-weekly triple hormone receptor agonist targeting GIP, GLP-1, and glucagon receptors, developed |
| | by Eli Lilly. At Week 80, retatrutide 12 mg produced a mean body weight reduction of 25.9% (efficacy estimand) versus 2.2% with |
| | placebo. In the 104-week extension, participants lost up to an average of 30.3% of initial body weight (RETA 12 mg/MTD). |
| | Retatrutide was generally well-tolerated; GI adverse events were the most common adverse events.", "url": |
| | "https\://lilly.com/hcp/congresses/ada-2026/dv039292-triumph-1", "status": "Completed", "sponsor": { "@type": |
| | "Organization", "@id": "https\://www\.lilly.com", "name": "Eli Lilly and Company", "url": |
| | "https\://www\.lilly.com" }, "healthCondition": \[ { "@type": "MedicalCondition", "@id": |
| | "https\://lilly.com/hcp/congresses/ada-2026/dv039292-triumph-1#obesity", "name": "Obesity", "alternateName": "BMI |
| | ≥30 kg/m²", "code": { "@type": "MedicalCode", "code": "E66", "codingSystem": "ICD-10" |
| | } }, { "@type": "MedicalCondition", "@id": |
| | "https\://lilly.com/hcp/congresses/ada-2026/dv039292-triumph-1#osa", "name": "Obstructive Sleep Apnea", |
| | "alternateName": "OSA", "code": { "@type": "MedicalCode", "code": "G47.33", "codingSystem": |
| | "ICD-10" } }, { "@type": "MedicalCondition", "@id": |
| | "https\://lilly.com/hcp/congresses/ada-2026/dv039292-triumph-1#knee-oa", "name": "Knee Osteoarthritis", |
| | "alternateName": "Knee OA", "code": { "@type": "MedicalCode", "code": "M17", "codingSystem": |
| | "ICD-10" } } ], "relevantSpecialty": \[ { "@type": "MedicalSpecialty", "name": |
| | "Endocrinology" }, { "@type": "MedicalSpecialty", "name": "Obesity Medicine" }, { |
| | "@type": "MedicalSpecialty", "name": "Pulmonology" }, { "@type": "MedicalSpecialty", "name": |
| | "Rheumatology" } ], "recognizingAuthority": { "@type": "Organization", "@id": |
| | "https\://www\.diabetes.org", "name": "American Diabetes Association", "url": "https\://www\.diabetes.org" } }, |
| | "hasPart": { "@type": "FAQPage", "@id": "https\://lilly.com/hcp/congresses/ada-2026/dv039292-triumph-1#faq", |
| | "mainEntity": \[ { "@type": "Question", "name": "What is retatrutide?", "acceptedAnswer": { |
| | "@type": "Answer", "text": "Retatrutide is an investigational once-weekly subcutaneous injectable developed by Eli |
| | Lilly. It is a triple hormone receptor agonist that simultaneously targets the GIP (glucose-dependent insulinotropic polypeptide), |
| | GLP-1 (glucagon-like peptide-1), and glucagon receptors. This triple mechanism is designed to reduce body weight by decreasing |
| | appetite, increasing energy expenditure, and improving metabolic function. In the Phase 3 TRIUMPH-1 trial, retatrutide 12 mg |
| | produced a mean body weight reduction of 25.9% at 80 weeks and up to 30.3% at 104 weeks in adults with obesity." } |
| | }, { "@type": "Question", "name": "How much weight can patients lose with retatrutide?", |
| | "acceptedAnswer": { "@type": "Answer", "text": "In the Phase 3 TRIUMPH-1 trial, adults with obesity treated |
| | with retatrutide 12 mg lost a mean of 25.9% of their body weight at 80 weeks (efficacy estimand) versus 2.2% with placebo. In the |
| | 104-week extension, participants on retatrutide 12 mg lost an average of 30.3% of their initial body weight. At 80 weeks, 97.3% of |
| | participants on retatrutide 12 mg achieved at least 5% weight loss, 76.2% achieved at least 20% weight loss, and 45.3% achieved at |
| | least 30% weight loss. Additionally, 65.3% of participants on retatrutide 12 mg achieved a BMI below 30 kg/m², compared to 7.6% on |
| | placebo." } }, { "@type": "Question", "name": "How is retatrutide administered?", |
| | "acceptedAnswer": { "@type": "Answer", "text": "Retatrutide is administered as a once-weekly subcutaneous |
| | injection. In the TRIUMPH-1 trial, dosing began at 2 mg and was gradually escalated over 16 weeks to target maintenance doses of 4 |
| | mg, 9 mg, or 12 mg once weekly. This gradual dose escalation approach is designed to improve tolerability, particularly for |
| | gastrointestinal side effects." } }, { "@type": "Question", "name": "What are the side effects |
| | of retatrutide?", "acceptedAnswer": { "@type": "Answer", "text": "The most common adverse events with |
| | retatrutide in the TRIUMPH-1 trial were gastrointestinal in nature, including nausea (42.4% with 12 mg vs 14.8% with placebo), |
| | diarrhea (32.0% vs 13.5%), constipation (26.1% vs 10.9%), and vomiting (25.3% vs 4.8%). These GI events were predominantly mild to |
| | moderate in severity and occurred mainly during the dose escalation period. Other common adverse events included decreased |
| | appetite, headache, fatigue, and dizziness. Adverse events leading to treatment discontinuation occurred in 11.3% of participants |
| | on retatrutide 12 mg versus 4.9% on placebo, with GI events accounting for 4.6% of discontinuations in the 12 mg group." } |
| | }, { "@type": "Question", "name": "Who is eligible for retatrutide treatment?", |
| | "acceptedAnswer": { "@type": "Answer", "text": "In the TRIUMPH-1 Phase 3 trial, retatrutide was studied in |
| | adults with obesity, defined as a BMI of 30 kg/m² or higher. The trial enrolled 2339 participants with a mean baseline BMI of 40 |
| | kg/m² and mean body weight of 248.5 lbs (112.7 kg). The study included participants across all obesity classes: Class 1 (BMI |
| | 30–<35, 20.6%), Class 2 (BMI 35–<40, 35.2%), and Class 3 (BMI ≥40, 42.1%). Disease-specific sub-groups included patients with |
| | obstructive sleep apnea (N=243) and knee osteoarthritis (N=574). Retatrutide is investigational and not yet approved; eligibility |
| | for any future approved indication will be defined by prescribing information." } }, { "@type": |
| | "Question", "name": "How does retatrutide compare to other GLP-1 receptor agonists?", "acceptedAnswer": { |
| | "@type": "Answer", "text": "Unlike existing GLP-1 receptor agonists (such as semaglutide) or dual GIP/GLP-1 receptor |
| | agonists (such as tirzepatide), retatrutide is a triple hormone receptor agonist that additionally activates the glucagon |
| | receptor. This added glucagon receptor activity is thought to increase energy expenditure, which may contribute to retatrutide's |
| | greater weight loss versus agents targeting fewer receptors. In the TRIUMPH-1 trial, retatrutide 12 mg achieved a mean body weight |
| | reduction of 25.9% at 80 weeks and 30.3% at 104 weeks — among the highest weight loss results reported in a Phase 3 obesity trial |
| | to date. Retatrutide is investigational; head-to-head comparative trials with other agents have not been completed." } |
| | } ] } } |
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| modified-time | 2026-06-16T15:28:19.400Z |
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| storybanner-templatetype | default |
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