Retatrutide results
Retatrutide results from the Phase 2 clinical trial (Jastreboff et al., published in the New England Journal of Medicine in June 2023) represent the most impressive weight loss data ever produced by a pharmacological intervention. This page presents the clinical data in detail — what was measured, at what doses, over what timeframe — and what the results mean for the future of obesity treatment.
Retatrutide results: Phase 2 headline data
The Phase 2 trial enrolled 338 adults with obesity (BMI ≥30) or overweight with at least one weight-related comorbidity (BMI ≥27). Participants were randomized to one of six retatrutide dose groups (1 mg, 4 mg slow escalation, 4 mg rapid, 8 mg slow, 8 mg rapid, or 12 mg) or placebo for 48 weeks. The primary endpoint was percent change in body weight from baseline.
| Dose | Mean weight loss (%) | Participants losing ≥15% | Participants losing ≥20% |
|---|---|---|---|
| Placebo | 2.1% | 3% | 0% |
| 1 mg | 8.7% | ~15% | ~5% |
| 4 mg | 17.1% | ~55% | ~30% |
| 8 mg | 22.8% | ~75% | ~55% |
| 12 mg | 24.2% | ~82% | ~63% |
At the 12 mg dose, the mean participant lost nearly a quarter of their body weight in under a year. For a 250-pound individual, this translates to approximately 60 pounds of weight loss. Over 80% of participants in the 12 mg group lost at least 15% of their body weight, and nearly two-thirds lost 20% or more. These numbers exceed the results of every other obesity drug in clinical development, including semaglutide (~15%) and tirzepatide (~22.5%).
Retatrutide results: the weight loss curve
Perhaps the most significant retatrutide result is what the weight loss curve shows at 48 weeks — or more precisely, what it doesn't show. In semaglutide trials, the weight loss curve begins to plateau at approximately 60 weeks, meaning further treatment produces diminishing additional weight loss. In the retatrutide Phase 2 trial, the weight loss curve at 48 weeks had not yet plateaued. Participants were still losing weight at a meaningful rate when the trial ended. This suggests that the 72-week Phase 3 TRIUMPH trials may produce weight loss percentages exceeding 24% — potentially reaching 26–28% or higher. If confirmed, this would establish retatrutide as the first compound to approach the weight loss achieved by bariatric surgery (~25–30%) through pharmacological means alone.
Retatrutide before and after: body composition
The Phase 2 trial measured total body weight change but did not include detailed body composition analysis (DEXA scans or similar). However, based on the known mechanisms of retatrutide's triple agonism and data from analogous compounds, the weight loss is expected to comprise approximately 60–75% fat mass and 25–40% lean mass — a ratio consistent with GLP-1 agonist-mediated weight loss. The glucagon receptor component may shift this ratio more favorably toward fat loss than semaglutide or tirzepatide, because glucagon specifically promotes lipolysis (fat breakdown) and thermogenesis (fat burning), but this has not been confirmed with composition data specific to retatrutide.
Retatrutide before and after body composition changes at the 12 mg dose over 48 weeks would include, for a typical 250-pound participant, approximately 60 pounds of total weight loss, an estimated 36–45 pounds of fat loss, an estimated 15–24 pounds of lean mass loss, significant reduction in visceral (abdominal) fat, and measurable waist circumference reduction. Phase 3 trials with body composition endpoints will provide more precise data. For now, the before-and-after projections are extrapolated from the overall weight loss data and the known body composition effects of the compound's receptor targets.
Retatrutide results: metabolic improvements
Beyond weight loss, the Phase 2 trial showed significant metabolic improvements in the retatrutide groups. HbA1c decreased substantially in participants with type 2 diabetes (the compound is also being studied as a diabetes treatment). Fasting glucose improved across all dose groups. Lipid profiles improved — reductions in triglycerides and LDL cholesterol. Liver fat content decreased, particularly at higher doses — consistent with the glucagon receptor's role in hepatic lipid oxidation. Blood pressure decreased, consistent with the cardiovascular benefits observed with other GLP-1 agonists. These metabolic results support retatrutide's potential as a treatment for metabolic syndrome broadly, not just obesity in isolation.
Retatrutide results: what Phase 3 TRIUMPH will tell us
The Phase 3 TRIUMPH program consists of multiple trials designed to confirm the Phase 2 results in larger populations and establish the data package for FDA submission. TRIUMPH-1 enrolls approximately 2,000 adults with obesity for 72 weeks at doses up to 12 mg and will provide the primary weight loss efficacy data for FDA submission. TRIUMPH-2 focuses on adults with obesity and type 2 diabetes. TRIUMPH-3 will examine weight maintenance after initial weight loss. Cardiovascular outcome data may come from a dedicated CVOT (cardiovascular outcomes trial), depending on FDA requirements and Eli Lilly's regulatory strategy.
How much weight can you lose on retatrutide?
The Phase 2 trial demonstrated 24.2% mean weight loss at the 12 mg dose over 48 weeks. For a 250-pound individual, this equals approximately 60 pounds. The weight loss curve had not plateaued at 48 weeks, suggesting that longer treatment (72+ weeks) may produce even greater reductions. Individual results vary — some participants lost more than 30% of body weight while others lost less than 15%.
How fast does retatrutide work?
Weight loss begins within the first 4 weeks of treatment, even at the starting dose of 2 mg. Meaningful weight loss (5%+) is typically achieved by 12 weeks as the dose escalates to therapeutic levels. The most dramatic weight loss occurs between weeks 12–36 when the full dose is reached and sustained. The rate of loss slows after 36–48 weeks but does not stop entirely — the Phase 2 curve was still declining at study end.
Are retatrutide results permanent?
Weight loss with GLP-1 agonists is generally not permanent after discontinuation. Studies with semaglutide and tirzepatide show that approximately two-thirds of lost weight is regained within 1–2 years of stopping treatment. There is no reason to expect retatrutide would be different — the compound treats the metabolic drivers of obesity but does not cure the underlying biology. Long-term or indefinite treatment may be required to maintain results, similar to medications for hypertension or diabetes.