Trial Outcomes Data
Structured summary of key outcomes from all retatrutide clinical trials, including primary endpoints, key results, and statistical significance across Phase 1–3 studies.
Trial Outcomes Summary
| Trial | Phase | Primary Endpoint | Key Result | Significance |
|---|---|---|---|---|
| First-in-Human Study | Phase 1 | Safety and tolerability (adverse events, vital signs, laboratory parameters) | Half-life: ~6 days | Supporting once-weekly subcutaneous dosing |
| Phase 1 Japan Study | Phase 1 | Safety and tolerability in Japanese population | Results pending | — |
| Phase 1b MAD Trial | Phase 1 | Safety and tolerability | Placebo-adjusted HbA1c change (12 weeks): -1.2% to -1.6% | Significant in the 3 mg, 3/6 mg and 3/6/9/12 mg groups |
| Phase 2 Body Composition Substudy | Phase 2 | Percent change in total body fat mass from baseline to week 36 (DXA) | Fat mass reduction (8 mg pooled, 36 weeks): -26.1% | Versus -4.5% on placebo and -2.6% on dulaglutide 1.5 mg |
| Phase 2 CKD Trial | Phase 2 | Change in measured glomerular filtration rate (mGFR, iohexol clearance) from baseline to week 24 | Results pending | — |
| Phase 2 MASLD Substudy | Phase 2 | Mean relative change in liver fat (MRI-PDFF) from baseline to week 24 | Relative liver fat change (12 mg, 24 weeks): -82.4% | Primary endpoint; placebo +0.3% |
| Phase 2 Obesity Trial | Phase 2 | Percent change in body weight from baseline at 24 weeks | Mean weight loss (12 mg, 48 weeks): -24.2% | Highest reported weight loss for any pharmaceutical agent in Phase 2 |
| Phase 2 Type 2 Diabetes Trial | Phase 2 | Change in HbA1c from baseline at 24 weeks | HbA1c reduction (12 mg, 24 weeks): -2.02% | Primary endpoint; mean baseline about 8.3% |
| SYNERGY-OUTCOMES | Phase 3 | Prevention of Major Adverse Liver Outcomes (MALO) | Results pending | — |
| TRANSCEND-T2D-1 | Phase 3 | Change in HbA1c from baseline at 40 weeks | HbA1c reduction (12 mg, from baseline 7.9%): -1.94 percentage points | vs -0.81 with placebo; glycemic control comparable to tirzepatide in the SURPASS program |
| TRANSCEND-T2D-2 | Phase 3 | Change from baseline in HbA1c at 80 weeks | A1C change at 80 weeks (9 mg and 12 mg, efficacy estimand): -2.2 points | vs -1.8 points with semaglutide 2 mg (Ozempic); mean baseline A1C 8.3% |
| TRIUMPH-1 | Phase 3 | Percent change in body weight from baseline at 80 weeks | Mean weight loss (12 mg, 80 weeks, efficacy estimand): -28.3% (-70.3 lbs / -31.9 kg) | Primary endpoint met. Largest mean weight loss in any retatrutide pivotal trial in adults without diabetes. |
| TRIUMPH-2 | Phase 3 | Percent change in body weight from baseline at 80 weeks | Mean weight loss (12 mg, 80 weeks, efficacy estimand): -20.8% (-49.6 lb / -22.5 kg) | Primary endpoint met. Largest weight loss reported in a Phase 3 obesity trial restricted to people with type 2 diabetes. |
| TRIUMPH-3 | Phase 3 | Percent change in body weight from baseline at 80 weeks | Mean weight loss (12 mg, 80 weeks, efficacy estimand): -22.6% (-55.8 lb) | Primary endpoint met in a high-risk population with a mean baseline BMI of 40.4 |
| TRIUMPH-4 | Phase 3 | Percent change in body weight from baseline at 68 weeks | Mean weight loss (12 mg, 68 weeks): -28.7% | Above the Phase 2 result of -24.2% at 48 weeks; the largest mean loss reported in a Phase 3 obesity trial at the time |
| TRIUMPH-9 (Dose Escalation Optimization) | Phase 3 | Efficacy and safety of different dose escalation schemes | Results pending | Trial ongoing — results not yet available |
| TRIUMPH-Outcomes | Phase 3 | Time to first occurrence of MACE (cardiovascular death, non-fatal MI, non-fatal stroke) | Results pending | Trial ongoing — results not yet available |
Data sourced from published trial results, ClinicalTrials.gov registrations, press releases and conference presentations. Phase 3 figures are topline results as announced by Eli Lilly unless a peer-reviewed publication is cited.
Detailed Results by Trial
First-in-Human Study
Phase 1 · n=45
| Metric | Value | Context |
|---|---|---|
| Half-life | ~6 days | Supporting once-weekly subcutaneous dosing |
| Common adverse events | GI events (nausea, vomiting, diarrhea) | Consistent with GLP-1 receptor agonist class effects |
| Dose-proportional PK | Yes | Linear pharmacokinetics across tested dose range |
| Early pharmacodynamic signal | Glucose reduction and weight loss observed | Preliminary evidence of biological activity |
Phase 1b MAD Trial
Phase 1 · n=72
| Metric | Value | Context |
|---|---|---|
| Placebo-adjusted HbA1c change (12 weeks) | -1.2% to -1.6% | Significant in the 3 mg, 3/6 mg and 3/6/9/12 mg groups |
| Placebo-adjusted body weight change (3/6/9/12 mg, 12 weeks) | -8.96 kg | Largest of the dose groups; weight loss appeared dose dependent |
| Terminal half-life | ~6 days | Supports once-weekly dosing |
| Median tmax | 12-48 hours | Time to peak plasma concentration |
Phase 2 Body Composition Substudy
Phase 2 · n=189
| Metric | Value | Context |
|---|---|---|
| Fat mass reduction (8 mg pooled, 36 weeks) | -26.1% | Versus -4.5% on placebo and -2.6% on dulaglutide 1.5 mg |
| Fat mass reduction (12 mg, 36 weeks) | -23.2% | Difference from placebo -18.7 percentage points |
| Lean mass share of weight lost | Similar to other obesity treatments | Authors' conclusion |
Phase 2 MASLD Substudy
Phase 2 · n=98
| Metric | Value | Context |
|---|---|---|
| Relative liver fat change (12 mg, 24 weeks) | -82.4% | Primary endpoint; placebo +0.3% |
| Relative liver fat change (12 mg, 48 weeks) | -86.0% | Placebo -4.6%; fewer participants had week 48 scans |
| Normal liver fat below 5% (12 mg) | 86% at 24 weeks, 93% at 48 weeks | Placebo 0% at 24 weeks |
| Relative liver fat change (8 mg, 24 weeks) | -81.4% | 79% reached normal liver fat |
Phase 2 Obesity Trial
Phase 2 · n=338
| Metric | Value | Context |
|---|---|---|
| Mean weight loss (12 mg, 48 weeks) | -24.2% | Highest reported weight loss for any pharmaceutical agent in Phase 2 |
| Mean weight loss (8 mg, 48 weeks) | -22.8% | Second-highest dose |
| Participants ≥5% weight loss (12 mg) | 100% | All participants at highest dose achieved clinically meaningful loss |
| Participants ≥15% weight loss (12 mg) | ~83% | Majority exceeded surgical-level threshold |
| Liver fat reduction (12 mg, 24 weeks) | -82.4% relative change | MRI-PDFF, in the 98-person MASLD substudy (Sanyal, Nature Medicine 2024) |
| Treatment discontinuation due to AEs (12 mg) | 16% | vs 0% on placebo; gastrointestinal events were the most common reason |
Phase 2 Type 2 Diabetes Trial
Phase 2 · n=281
| Metric | Value | Context |
|---|---|---|
| HbA1c reduction (12 mg, 24 weeks) | -2.02% | Primary endpoint; mean baseline about 8.3% |
| HbA1c 7.0% or less at 24 weeks (4 mg and above) | 53-86% | Versus 22% on placebo |
| Weight loss (12 mg, 36 weeks) | -16.9% | Substantial weight loss in T2D population |
| HbA1c reduction vs. dulaglutide | Superior at 8 mg (2 mg start) and 12 mg | Active comparator was dulaglutide 1.5 mg |
TRANSCEND-T2D-1
Phase 3 · n=537
| Metric | Value | Context |
|---|---|---|
| HbA1c reduction (12 mg, from baseline 7.9%) | -1.94 percentage points | vs -0.81 with placebo; glycemic control comparable to tirzepatide in the SURPASS program |
| Weight loss (12 mg) | -15.3% (-15.1 kg) | vs -2.6% placebo; substantially greater than tirzepatide in T2D populations |
| Reaching HbA1c below 7.0% | 82-89% across doses | 75-83% reached the tighter ≤6.5% target |
| Publication | The Lancet, June 6, 2026 | Presented simultaneously at ADA 2026 Scientific Sessions, New Orleans |
TRANSCEND-T2D-2
Phase 3 · n=1298
| Metric | Value | Context |
|---|---|---|
| A1C change at 80 weeks (9 mg and 12 mg, efficacy estimand) | -2.2 points | vs -1.8 points with semaglutide 2 mg (Ozempic); mean baseline A1C 8.3% |
| Body weight change at 80 weeks (efficacy estimand) | -19.5% (9 mg), -20.9% (12 mg) | vs -9.4% with semaglutide 2 mg (Ozempic) |
| Diarrhea, the most common side effect | 28.3% (9 mg), 32.7% (12 mg) | vs 26.4% with semaglutide 2 mg |
| Source | Lilly topline announcement, October 28, 2026 | Not yet presented at a medical meeting or peer reviewed |
TRIUMPH-1
Phase 3 · n=2339
| Metric | Value | Context |
|---|---|---|
| Mean weight loss (12 mg, 80 weeks, efficacy estimand) | -28.3% (-70.3 lbs / -31.9 kg) | Primary endpoint met. Largest mean weight loss in any retatrutide pivotal trial in adults without diabetes. |
| Mean weight loss (9 mg, 80 weeks, efficacy estimand) | -25.9% (-64.4 lbs / -29.2 kg) | Confirms efficacy at a lower dose with improved tolerability |
| Mean weight loss (4 mg, 80 weeks, efficacy estimand) | -19.0% (-47.2 lbs / -21.4 kg) | Lowest dose still exceeded historical semaglutide 2.4 mg results |
| Placebo weight loss (80 weeks, efficacy estimand) | -2.2% | Typical placebo response for this trial design |
| Participants achieving ≥25% weight loss (12 mg) | 62.5% | Bariatric-surgery-range outcome in a majority of participants |
| Participants achieving ≥30% weight loss (12 mg) | 45.3% | Nearly half of 12 mg participants reached threshold previously associated only with bariatric surgery |
| Dysesthesia incidence (12 mg) | 12.5% | Notably lower than the 20.9% reported in TRIUMPH-4 — same dose, different population |
| Discontinuation due to adverse events (12 mg) | 11.3% | Higher than placebo (4.9%); modest given the magnitude of weight loss |
TRIUMPH-2
Phase 3 · n=1152
| Metric | Value | Context |
|---|---|---|
| Mean weight loss (12 mg, 80 weeks, efficacy estimand) | -20.8% (-49.6 lb / -22.5 kg) | Primary endpoint met. Largest weight loss reported in a Phase 3 obesity trial restricted to people with type 2 diabetes. |
| Mean weight loss (9 mg, 80 weeks) | -19.1% (-45.4 lb) | Within two percentage points of the 12 mg arm, with the highest discontinuation rate of the three doses |
| Mean weight loss (4 mg, 80 weeks) | -12.7% (-29.8 lb) | Lowest dose; still three times the placebo response |
| Placebo weight loss (80 weeks) | -4.0% (-9.3 lb) | Higher placebo response than in TRIUMPH-1 (-2.2%) |
| A1C change (4 / 9 / 12 mg vs placebo) | -1.4 / -1.6 / -1.5 points vs -0.2 | From a baseline A1C of 7.7%; no additional glycemic benefit at 12 mg over 9 mg |
| Dysesthesia (4 / 9 / 12 mg vs placebo) | 4.5% / 5.6% / 7.3% vs 0.7% | Markedly lower than TRIUMPH-1 (12.5% at 12 mg) and TRIUMPH-4 (20.9%) |
| Discontinuation due to adverse events (4 / 9 / 12 mg vs placebo) | 3.8% / 11.6% / 7.7% vs 4.9% | Non-monotonic: the 9 mg arm discontinued more often than the 12 mg arm |
TRIUMPH-3
Phase 3 · n=1949
| Metric | Value | Context |
|---|---|---|
| Mean weight loss (12 mg, 80 weeks, efficacy estimand) | -22.6% (-55.8 lb) | Primary endpoint met in a high-risk population with a mean baseline BMI of 40.4 |
| Mean weight loss (9 mg, 80 weeks) | -21.6% (-52.7 lb) | Within one percentage point of the 12 mg arm |
| Placebo weight loss (80 weeks) | -3.2% (-7.7 lb) | Typical placebo response for a lifestyle-supported trial |
| Triglycerides (12 mg) | -37.0% | Largest lipid effect reported in the program |
| Systolic blood pressure (12 mg) | -9.3 mmHg | Comparable to a single antihypertensive agent |
| hsCRP (12 mg) | -51.2% | Halving of the inflammatory marker most strongly linked to cardiovascular events |
| MACE-5 events (pooled retatrutide vs placebo, exploratory) | 44 vs 52; HR 0.82 (95% CI 0.55–1.22) | Not statistically significant. TRIUMPH-3 was not powered for cardiovascular outcomes; TRIUMPH-Outcomes is. |
| Dysesthesia (9 / 12 mg vs placebo) | 6.4% / 6.4% vs 1.3% | Lower than TRIUMPH-1 (12.5%) and TRIUMPH-4 (20.9%) at 12 mg |
| Discontinuation due to adverse events (9 / 12 mg vs placebo) | 9.8% / 13.5% vs 4.8% | Similar to the 11.3% seen at 12 mg in TRIUMPH-1 |
TRIUMPH-4
Phase 3 · n=445
| Metric | Value | Context |
|---|---|---|
| Mean weight loss (12 mg, 68 weeks) | -28.7% | Above the Phase 2 result of -24.2% at 48 weeks; the largest mean loss reported in a Phase 3 obesity trial at the time |
| Knee OA pain reduction (WOMAC, efficacy estimand) | -4.5 points (9 mg, -75.8%), -4.4 points (12 mg) | vs -2.4 points (-40.3%) on placebo |
| Mean weight loss (9 mg, 68 weeks) | -26.4% | Lower of the two Phase 3 doses |
| Participants losing at least 25% of body weight | 47.7% (9 mg), 58.6% (12 mg) | vs 1.3% on placebo |
| Dysesthesia incidence (12 mg) | 20.9% | New safety signal — sensory nerve disturbance, vs 0.7% placebo |
Cross-Trial Efficacy Comparison (Phase 2, Highest Dose)
| Metric | Obesity Trial (12 mg, 48 wk) | T2D Trial (12 mg, 36 wk) |
|---|---|---|
| Weight loss | -24.2% | -16.9% |
| HbA1c reduction | Not primary endpoint | -2.02% |
| Liver fat reduction | ~82% relative reduction | Not reported |
| Participants achieving ≥5% weight loss | ~100% | Not reported |
| Participants achieving HbA1c <7.0% | Not primary endpoint | ~95% |
| Discontinuation due to AEs | ~16% | ~10% |
Cross-trial comparisons are illustrative only. Differences in study populations, trial duration, and endpoints limit direct comparison.
How to Interpret This Data
Understanding Primary Endpoints
The primary endpoint is the main outcome measure a trial is designed to evaluate. It is specified before the trial begins and determines whether the trial is considered a success. In obesity trials, the primary endpoint is typically the percent change in body weight from baseline at a specific time point. In type 2 diabetes trials, the primary endpoint is usually the change in HbA1c (a measure of average blood glucose over 2–3 months). Phase 1 trials focus on safety, tolerability, and pharmacokinetics rather than efficacy.
Statistical Significance
A result is considered statistically significant when the probability that it occurred by chance alone (the p-value) is below a predetermined threshold, typically p<0.05. This means there is less than a 5% probability that the observed difference between treatment and placebo groups is due to random variation. In retatrutide Phase 2 trials, most primary comparisons achieved p<0.001, indicating extremely strong statistical evidence. However, statistical significance does not automatically imply clinical meaningfulness — a result can be statistically significant but too small to matter in practice.
Key Results vs. Primary Endpoints
The "Key Result" column in the summary table highlights the single most notable finding from each trial, which may or may not be the primary endpoint result. For example, the headline weight loss figure from the obesity trial is the 48-week result, which was technically a key secondary endpoint (the primary endpoint was measured at 24 weeks). This distinction matters for regulatory purposes but is less important for understanding the drug's clinical potential.
Phase 3 Trials: Topline Versus Published Results
The five pivotal Phase 3 trials (TRIUMPH-1 to -4 and TRANSCEND-T2D-1) have all reported. TRANSCEND-T2D-1 (The Lancet, June 6, 2026), TRIUMPH-1 (NEJM, September 29, 2026) and TRIUMPH-2 (The Lancet, September 29, 2026) have peer-reviewed publications; the other TRIUMPH figures, and most figures in the trial pages, are topline results from Eli Lilly press releases and the ADA 2026 presentation, and may be refined in the full papers. TRANSCEND-T2D-2 (head-to-head against semaglutide 2 mg) reported topline results on October 28, 2026: A1C −2.2 points at 12 mg versus −1.8, weight −20.9% versus −9.4% at 80 weeks. TRIUMPH-Outcomes and the SYNERGY/MACELD liver trials remain ongoing; their endpoints are listed from ClinicalTrials.gov registrations.
Limitations of Cross-Trial Comparisons
Comparing results across different trials requires caution. Differences in patient populations (obesity vs. type 2 diabetes), trial duration, dosing schedules, background therapies, and endpoint definitions can all influence outcomes. The cross-trial comparison table above is intended to provide a general overview and should not be used to draw definitive conclusions about relative efficacy across indications. Only head-to-head trials with matched designs can provide reliable comparative data.