Retatrutide Weight Loss Results: What the Phase 2 Trial Showed and What Phase 3 Will Tell Us

When Eli Lilly published Phase 2 retatrutide data in the New England Journal of Medicine in June 2023, the response among obesity researchers was striking. In a field accustomed to incremental progress, a drug that produced 24.2% average body weight loss at 48 weeks — when most weight-loss trials ran to 68–72 weeks — represented a step change. Three years later, the Phase 3 data have confirmed and exceeded that signal.

This article is a complete account of what the trials showed: the Phase 2 dose-finding study, the TRIUMPH-1 Phase 3 readout reported in May 2026, what the numbers mean in context, and what the remaining Phase 3 trials will determine before an FDA filing. For a broader overview of where retatrutide fits among next-generation compounds, see our article on next-generation weight loss medications.

The Phase 2 Trial: Design and Key Results

The Phase 2 dose-finding trial (NCT04881760), published in the NEJM by Jastreboff et al. in June 2023, was a 48-week, randomized, double-blind, placebo-controlled study in 338 adults with obesity (BMI ≥30) or overweight (BMI 27–30 with at least one weight-related condition) who did not have type 2 diabetes. Participants were randomized to weekly subcutaneous injections of retatrutide at doses of 1 mg, 4 mg, 8 mg, or 12 mg, or placebo.

The primary endpoint was the percentage change in body weight from baseline to week 24. The 48-week secondary endpoint proved to be the more consequential finding.

Dose-Response Results at 48 Weeks

The weight loss results across dose groups at 48 weeks were as follows:

• 12 mg dose: Mean 24.2% body weight loss (~57.8 lbs / 26.2 kg from an average baseline weight)
• 8 mg dose: Mean 22.8% body weight loss
• 4 mg dose: Mean 17.5% body weight loss
• 1 mg dose: Mean 8.7% body weight loss
• Placebo: Mean 2.1% weight change

The 12 mg result was the largest mean weight loss reported for any pharmacological agent in a clinical trial at that duration. To put it in context: semaglutide (Wegovy) produced approximately 14.9% weight loss at 68 weeks in the STEP-1 trial, and tirzepatide (Zepbound) produced 20.9% at 72 weeks in SURMOUNT-1 — at longer endpoints than retatrutide's 48 weeks.

The Unreached Plateau

One of the most clinically significant observations from the Phase 2 data was that weight loss trajectories had not flattened at week 48. In prior GLP-1 trials, weight loss curves typically plateau by 36–40 weeks as appetite suppression reaches a steady state. In retatrutide participants, the slope of weight loss remained downward at the end of the study period, indicating that the full treatment effect had not been captured. This observation drove the decision to extend the TRIUMPH-1 Phase 3 primary endpoint to 80 weeks — and to add a 104-week blinded extension for the high-BMI subgroup.

Responder Analysis

Among participants on the 12 mg dose at 48 weeks, 26% had achieved at least 30% total body weight loss. This threshold is clinically significant because it had previously been associated exclusively with bariatric surgery procedures such as Roux-en-Y gastric bypass. The Phase 2 data raised the possibility — confirmed by Phase 3 — that pharmacological treatment could produce surgical-range outcomes in a meaningful proportion of patients.

Phase 2 Safety Profile

The adverse event profile in Phase 2 was dominated by gastrointestinal effects — the same class of events seen with semaglutide and tirzepatide. Nausea, vomiting, diarrhea, and constipation were the most common adverse events and were rated mild to moderate in severity. Rates declined over time as participants adjusted to their maintenance doses.

The unique safety consideration for retatrutide — compared to dual GLP-1/GIP agonists like tirzepatide — was the glucagon receptor component. Glucagon receptor agonism raises energy expenditure through thermogenic mechanisms but also has cardiovascular effects. The Phase 2 data reported mean resting heart rate increases of approximately 5–8 beats per minute at the highest dose. No serious cardiac adverse events were attributed to retatrutide in Phase 2, but this signal was closely watched heading into Phase 3.

The trial also showed modest improvements in liver fat content, blood pressure, and lipid profiles — cardiovascular risk factor changes consistent with meaningful weight loss.

The TRIUMPH Phase 3 Program: Overview

Eli Lilly initiated the TRIUMPH Phase 3 program in 2023. The program comprises multiple trials spanning different populations and indications:

• TRIUMPH-1 (NCT05929066): Obesity/overweight without diabetes — the pivotal registration trial. Topline results reported May 21, 2026.
• TRIUMPH-2 (NCT05929079): Obesity with type 2 diabetes. Data expected 2026.
• TRIUMPH-3 (NCT05882045): Obesity with established cardiovascular disease. Data expected 2026–2027.
• TRIUMPH-4 (NCT05931367): Obesity with knee osteoarthritis. First Phase 3 readout, December 2025 — positive results, 28.7% weight loss at 12 mg/68 weeks.
• TRIUMPH-6 (NCT06859268): Weight maintenance.
• TRIUMPH-Outcomes (NCT06383390): Cardiovascular outcomes trial in ~10,000 participants. Long-running, results expected 2028.

The TRANSCEND-T2D-1 Phase 3 diabetes trial (reported March 2026) also provided important data: HbA1c reductions of 1.7–2.0 percentage points and 11.5–16.8% weight loss in adults with type 2 diabetes, results presented in full at the ADA 2026 Scientific Sessions in June.

TRIUMPH-1: The Pivotal Obesity Phase 3 Trial

TRIUMPH-1 enrolled 2,339 adults with obesity (BMI ≥30) or overweight (BMI ≥27 with at least one weight-related comorbidity) and without type 2 diabetes. Participants were randomized 1:1:1:1 to once-weekly subcutaneous retatrutide at 4 mg, 9 mg, or 12 mg, or placebo. All active-treatment arms used a stepwise escalation from a 2 mg starting dose, increasing every four weeks.

The primary endpoint was the percentage change in body weight at week 80. TRIUMPH-1 also incorporated two nested basket studies evaluating retatrutide in participants with moderate-to-severe obstructive sleep apnea and knee osteoarthritis pain.

Primary Results at 80 Weeks

Eli Lilly reported topline results on May 21, 2026 — with full data presented at the ADA 2026 Scientific Sessions on June 6, 2026:

• 12 mg dose: Mean 28.3% body weight loss (~70.3 lbs from a baseline mean of 248.5 lbs)
• 9 mg dose: Mean 25.9% body weight loss (~64.4 lbs)
• 4 mg dose: Mean 19.0% body weight loss (~47.2 lbs)
• Placebo: Mean 2.2% weight change

All three active doses met the trial's primary and key secondary endpoints. The 12 mg result is the highest mean weight loss reported for any pharmacological treatment in a Phase 3 obesity trial at the time of publication.

Categorical Responders

The responder analysis at the 12 mg dose at 80 weeks was as follows:

• 62.5% of participants achieved at least 25% body weight loss
• 45.3% achieved at least 30% body weight loss (the threshold associated with bariatric surgery)
• 27.2% achieved at least 35% body weight loss
• 65.3% of the 12 mg arm crossed back under a BMI of 30 at week 80

The 104-Week Extension

A pre-specified blinded extension enrolled 532 participants with a baseline BMI of 35 or above, who had tolerated their assigned dose and were escalated to the maximum tolerated dose (9 mg or 12 mg) for an additional 24 weeks. At week 104:

• 12 mg to maximum tolerated dose: mean 30.3% weight loss (~85.0 lbs)
• 9 mg to maximum tolerated dose: mean 29.5% weight loss (~80.7 lbs)
• 4 mg to maximum tolerated dose: mean 27.9% weight loss (~73.3 lbs)

The observation that even participants starting at the lowest dose who were subsequently escalated reached nearly 28% weight loss at 104 weeks underscores the importance of treatment duration in this class of drugs.

Cardiometabolic Secondary Endpoints

Beyond weight loss, TRIUMPH-1 reported favorable changes in cardiometabolic risk factors at 80 weeks in the 12 mg arm:

• Waist circumference: reduced by 24.1 cm (vs. 3.6 cm on placebo)
• Triglycerides: reduced by 41.0%
• Non-HDL cholesterol: reduced by 24.2%
• Systolic blood pressure: reduced by 12.3 mmHg
• High-sensitivity C-reactive protein (hsCRP): significantly reduced

These cardiometabolic improvements occurred alongside the weight loss and are consistent with changes seen in tirzepatide trials, though the TRIUMPH cardiovascular outcomes trial (TRIUMPH-Outcomes) running to 2028 will determine whether retatrutide reduces hard cardiovascular events as semaglutide did in the SELECT trial.

TRIUMPH-1 Safety Profile

The adverse event profile in TRIUMPH-1 was broadly consistent with the incretin drug class, with some important additions:

Gastrointestinal events at 12 mg: nausea (42.4%), diarrhea (32.0%), constipation (26.1%), vomiting (25.3%). These rates are higher than those seen with tirzepatide in SURMOUNT-1, likely reflecting the addition of glucagon receptor agonism. Rates were substantially lower in the 4 mg arm.

Dysesthesia: An abnormal skin sensation signal identified in Phase 2 recurred in TRIUMPH-1 at approximately 12.5% at the 12 mg dose versus 0.9% on placebo. Most cases were mild to moderate and resolved during treatment. The mechanism is believed to relate to glucagon receptor activation in peripheral neurons.

Urinary tract infections: A new safety signal in TRIUMPH-1 — UTIs occurred in 7.5–8.8% of retatrutide participants versus 5.3% on placebo, predominantly in women. The mechanism is not fully established.

Discontinuation due to adverse events: 4.1% at 4 mg (notably, below the 4.9% placebo rate), 6.9% at 9 mg, and 11.3% at 12 mg. The 4 mg discontinuation rate being lower than placebo — described by Lilly CMO Dan Skovronsky as "remarkable" — reinforces that the lower dose may represent an attractive efficacy-tolerability balance for many patients.

No cardiac or hepatic signals: Lilly reported no clinically significant cardiac arrhythmias or liver problems attributed to retatrutide in TRIUMPH-1. This was closely watched given the glucagon component and prior concerns about heart rate elevation from Phase 2.

The 4 mg Dose: An Underappreciated Finding

Much of the attention in TRIUMPH-1 went to the 28.3% result at 12 mg, but the 4 mg data deserve equal consideration. At 19.0% average weight loss with a discontinuation rate below placebo, the lowest dose represents a meaningful option for patients who cannot tolerate higher-dose escalation. For comparison, tirzepatide 5 mg in SURMOUNT-1 produced approximately 15% weight loss. A 4 mg retatrutide dose producing 19% with excellent tolerability may become the most commonly prescribed starting maintenance dose in clinical practice.

What Remaining Phase 3 Trials Will Determine

TRIUMPH-1 establishes the efficacy and safety profile of retatrutide in non-diabetic adults with obesity, which is the population most relevant to the obesity indication. But several important questions remain for the broader TRIUMPH program:

TRIUMPH-2 (T2D): Separate from TRANSCEND-T2D-1, TRIUMPH-2 will provide data on retatrutide in adults with type 2 diabetes and obesity. People with diabetes typically lose less weight on GLP-1 agents. Understanding the diabetic obesity population response is critical for labeling and prescribing guidance.

TRIUMPH-3 (CVD): The trial in adults with established cardiovascular disease will inform whether retatrutide can be safely used — and is beneficial — in high-cardiovascular-risk populations. Given the heart rate increases from glucagon agonism, this subpopulation data is especially relevant for clinicians. Results are expected in 2026–2027.

TRIUMPH-Outcomes: The long-running cardiovascular outcomes trial, with approximately 10,000 participants, will determine whether retatrutide reduces major adverse cardiovascular events (MACE) as injectable semaglutide did in the SELECT trial. This trial runs to approximately 2028 and will not be part of the initial NDA submission but will be important for post-market prescribing confidence.

For a detailed look at how the titration schedule from 2 mg to maintenance doses works, see our article on retatrutide titration schedule. For information on FDA approval timelines, see our retatrutide FDA approval date update.

Contextualizing the Numbers: What 28.3% Weight Loss Means

At a baseline mean weight of 248.5 lbs (112.7 kg) in TRIUMPH-1, a 28.3% loss translates to losing approximately 70 lbs. For a 250-lb person, that means reaching roughly 180 lbs at 80 weeks — well within normal BMI range for many heights. At 30.3% over 104 weeks, the same person would reach approximately 174 lbs.

Roux-en-Y gastric bypass produces approximately 25–30% body weight loss at one year. Sleeve gastrectomy produces approximately 20–25%. The TRIUMPH-1 data at 80 weeks places pharmacological retatrutide in direct overlap with bariatric surgery outcomes for a substantial proportion of patients — not just statistically, but in absolute terms that translate to clinical significance in terms of diabetes remission, joint loading, sleep apnea resolution, and cardiovascular risk reduction.

For a direct comparison of retatrutide and tirzepatide trial results, see our article on tirzepatide vs. retatrutide weight loss. For a head-to-head comparison including Mounjaro specifically, see retatrutide vs. Mounjaro.

Independent Analysis: Three Findings That Get Less Attention

The following three observations from the retatrutide trial data carry significant clinical and policy implications that extend beyond the headline numbers:

1. The treatment-duration effect is larger than appreciated

Phase 2 ran 48 weeks and produced 24.2% weight loss. Phase 3 ran 80 weeks and produced 28.3%. The 104-week extension produced 30.3%. Each additional treatment period produced additional meaningful weight loss. This is in stark contrast to earlier GLP-1 agents where the dose-response relationship was largely exhausted within 36–40 weeks. Retatrutide's triple-receptor mechanism may produce a slower, more sustained metabolic adaptation that does not plateau at the same point. The clinical implication: patients who remain on treatment and tolerate it well should continue to expect additional weight loss beyond the first year — something that was not reliably true with semaglutide-only agents.

2. The 4 mg dose inverts the typical tolerability-efficacy trade-off

In drug development, more efficacy typically comes at the cost of more side effects. The 4 mg retatrutide dose in TRIUMPH-1 breaks this pattern: at 19.0% weight loss with a discontinuation rate lower than placebo (4.1% vs. 4.9%), it produces substantially better efficacy than the highest doses of currently approved drugs while being better tolerated than an inactive control. This is not a common finding in Phase 3 trials and suggests the 4 mg dose may have a favorable real-world adherence profile that could produce better population-level outcomes than the 12 mg dose despite lower mean weight loss.

3. Bariatric surgery comparisons will be unavoidable — and the data support them

Clinical practice has long held that bariatric surgery is necessary for patients requiring more than 20% weight loss. TRIUMPH-1 definitively ends that threshold. With 45.3% of participants on 12 mg achieving at least 30% loss — the number traditionally associated with Roux-en-Y gastric bypass — clinicians will need to revise treatment algorithms that reserve surgery for patients who fail on pharmacological therapy. The question is no longer whether medication can match surgery; it is which patients, at what dose, for how long, and at what cost. Comparative effectiveness trials between retatrutide and bariatric procedures are a clinical priority.

Understanding the full mechanism behind these results requires understanding what triple agonism does at the receptor level. That explanation is in our article on triple agonist weight loss drugs.

Frequently Asked Questions

How much weight did people lose on retatrutide in Phase 2?

In the Phase 2 trial published in the New England Journal of Medicine in 2023, participants on the highest 12 mg dose lost an average of 24.2% of body weight at 48 weeks. The 8 mg dose produced 22.8% and the 4 mg dose produced 17.5%. Placebo participants lost 2.1%.

What did TRIUMPH-1 Phase 3 show for retatrutide weight loss?

TRIUMPH-1 reported topline results on May 21, 2026. At 80 weeks, participants on 12 mg lost an average of 28.3% of body weight (approximately 70.3 lbs). The 9 mg dose produced 25.9% and the 4 mg dose produced 19.0%. In a pre-specified 104-week extension for those with BMI ≥35, the 12 mg arm reached 30.3% average weight loss.

Why was weight loss still increasing at the end of the Phase 2 trial?

The 48-week Phase 2 trial ended while participants were still losing weight — the efficacy plateau had not been reached. This distinguished retatrutide from earlier GLP-1 agents, where loss curves typically flatten by week 36–40. The Phase 3 80-week endpoint was designed to capture more of the full weight loss trajectory.

What percentage of retatrutide patients reached 30% weight loss?

In Phase 2 at 48 weeks, 26% of participants on the 12 mg dose achieved at least 30% body weight loss. In TRIUMPH-1 Phase 3 at 80 weeks, 45.3% of the 12 mg arm reached that threshold. In the 104-week extension, the average weight loss itself exceeded 30% in the high-BMI subgroup.

What are the main side effects of retatrutide?

The most common adverse events in TRIUMPH-1 at the 12 mg dose were gastrointestinal: nausea (42.4%), diarrhea (32.0%), constipation (26.1%), and vomiting (25.3%). Dysesthesia (abnormal skin sensation) occurred in approximately 12.5% at the highest dose. Urinary tract infections emerged as a new safety signal at 7.5–8.8% vs. 5.3% on placebo. Most were mild to moderate.

How does retatrutide weight loss compare to tirzepatide?

Tirzepatide (Zepbound) produced 20.9% average weight loss at 72 weeks in SURMOUNT-1. Retatrutide produced 24.2% at 48 weeks in Phase 2 and 28.3% at 80 weeks in TRIUMPH-1. No direct head-to-head trial has been published, but a Phase 3 head-to-head study (TRIUMPH-5) is enrolling with results expected in late 2026.

When will retatrutide be available by prescription?

Retatrutide is not FDA-approved as of June 2026. Eli Lilly has confirmed it expects to submit a New Drug Application in late 2026. Under standard FDA review timelines (10–12 months), approval would be expected in late 2027, with commercial availability in late 2027 to early 2028.

Sources

1. Jastreboff AM, et al. "Triple–Hormone-Receptor Agonist Retatrutide for Obesity — Phase 2 Trial." New England Journal of Medicine, 2023. https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
2. Eli Lilly. "TRIUMPH-1 Phase 3 Topline Results." Press release, May 21, 2026. https://www.pharmaceutical-journal.com/article/news/phase-iii-retatrutide-study-demonstrates-30-weight-loss
3. Jastreboff AM. TRIUMPH-1 Full Data Presentation. ADA 2026 Scientific Sessions, June 6, 2026. https://www.pharmaceutical-technology.com/analyst-comment/ada26-retatrutide-unprecedented-weight-loss-phase-iii-triumph-1/
4. Lilly Press Release — Phase 2 NEJM Publication. June 26, 2023. https://www.prnewswire.com/news-releases/lillys-phase-2-retatrutide-results-published-in-the-new-england-journal-of-medicine-show-the-investigational-molecule-achieved-up-to-17-5-mean-weight-reduction-at-24-weeks-in-adults-with-obesity-and-overweight-301863690.html
5. Wilding JPH, et al. "Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)." NEJM, 2022. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
6. ClinicalTrials.gov. TRIUMPH-1 Study Record, NCT05929066. https://clinicaltrials.gov/study/NCT05929066
7. Medscape. "Retatrutide Data Show Dramatic Weight Loss, Other Benefits." ADA 2026 coverage, June 7, 2026. https://www.medscape.com/viewarticle/retatrutide-data-show-dramatic-weight-loss-other-benefits-2026a1000iz0