The headline: −24.2% at 48 weeks#
The Phase 2 obesity trial reported the largest mean weight loss ever published for a pharmacologic obesity treatment.
In Lilly's Phase 2 obesity trial, adults with obesity (or overweight with at least one weight-related comorbidity) randomized to retatrutide 12 mg lost an average of 24.2% of body weight from baseline after 48 weeks. Placebo participants lost about 2.1%. [1]
Phase 2 obesity trial · 48 weeks
What the trial data shows
In Lilly's Phase 2 obesity trial (Jastreboff et al., NEJM 2023), participants on the highest dose lost an average of 24.2% of body weight after 48 weeks — among the largest reductions ever recorded for a pharmacologic agent.
Source: Jastreboff AM, et al. Triple Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med 2023; 389:514-526.
Results by dose#
A clear dose-response. Each step up produced more weight loss, with the gap between 8 mg and 12 mg the smallest — suggesting the curve may be approaching a ceiling.
- 1 mg — average weight loss ~8.7%
- 4 mg — average weight loss ~17.1%
- 8 mg — average weight loss ~22.8%
- 12 mg — average weight loss ~24.2%
- Placebo — average weight loss ~2.1%
Notably, even the 4 mg dose — which is closer to the lower end of the dose range — produced weight loss comparable to top-dose semaglutide. The maximally tolerated retatrutide dose has not yet been definitively established for the commercial label; Phase 3 doses are expected to mirror this range.
The plateau hadn't arrived at 48 weeks#
Most weight-loss drugs reach a plateau between 60 and 72 weeks. Phase 2 retatrutide curves were still trending down at trial end.
In published curves, weight loss continued to accumulate throughout the full 48-week study period. Tirzepatide and semaglutide trials, which ran 68 to 72 weeks, generally show the curves flattening in the second half of treatment.
The Phase 3 TRIUMPH-1 trial runs 76 weeks. That extra time will be the first opportunity to characterize where retatrutide plateaus and at what magnitude.
Proportion of responders at each threshold#
Headline averages can hide variability. Looking at how many participants hit specific weight-loss milestones gives a clearer clinical picture.
| Weight loss | Placebo | 4 mg | 8 mg | 12 mg |
|---|---|---|---|---|
| ≥ 5% | 22% | 84% | 95% | 100% |
| ≥ 10% | 9% | 65% | 91% | 93% |
| ≥ 15% | 3% | 48% | 75% | 83% |
| ≥ 20% | 0% | 24% | 50% | 63% |
| ≥ 25% | 0% | 7% | 17% | 26% |
Table 1 — Approximate proportions of participants achieving each threshold at week 48 · Source: Jastreboff et al., NEJM 2023
The standout statistic: about a quarter of participants on the 12 mg dose lost 25% or more of their body weight at 48 weeks. That magnitude of pharmacological weight loss has not been reported before in a published obesity-drug trial.
Subgroup analyses#
Effects were broadly consistent across baseline BMI, sex, and age in Phase 2 — but the trial was modest in size and Phase 3 will refine these signals.
Phase 2 enrollment was 338 participants, which limits the precision of subgroup analyses. Within those constraints, weight-loss effects were broadly similar across baseline BMI categories (≥30 vs. ≥35 vs. ≥40), sex, age, and race/ethnicity groups, with point estimates that overlap heavily.
The TRIUMPH program enrolls thousands of participants, which will support more meaningful subgroup analyses, including in participants with type 2 diabetes (whose response is typically attenuated relative to non-diabetic populations across the GLP-1 class).
Compared to tirzepatide and semaglutide#
Cross-trial comparison only — no head-to-head data exists. With that caveat, the magnitude advantage is consistent.
- Retatrutide 12 mg: ~24.2% at 48 wk (Phase 2)
- Tirzepatide 15 mg: ~20.9% at 72 wk (SURMOUNT-1) [2]
- Semaglutide 2.4 mg: ~14.9% at 68 wk (STEP 1) [3]
Different trials, different populations, different time points. The retatrutide number is from a smaller, shorter trial. Phase 3 readouts will determine whether the magnitude advantage holds at scale.
See retatrutide vs. tirzepatide and retatrutide vs. semaglutide for the full breakdowns.
What happens if you stop#
Pharmacological weight loss reverses when the drug is discontinued. Retatrutide is not yet studied for stop-and-restart patterns, but the GLP-1 class is well characterized here.
Across the GLP-1 class, weight regain is the rule, not the exception. The STEP 4 trial of semaglutide showed that when participants who had lost weight on semaglutide were re-randomized to placebo, they regained roughly two-thirds of their lost weight within a year.
Retatrutide-specific data on stop/restart patterns will come from extension studies and post-marketing experience. The practical implication for now is the same as for other GLP-1 drugs: treatment is generally a long-term commitment, not a short course.
What Phase 3 will refine#
Headline averages in Phase 2 are very large. Phase 3 will tell us how durable, how generalizable, and how reproducible these numbers are.
- Larger sample size — TRIUMPH-1 alone enrolls roughly 7x more participants than the Phase 2 obesity trial.
- Longer duration — 76 weeks vs. 48 weeks lets the plateau be characterized.
- Sicker populations — TRIUMPH-2 (T2D), TRIUMPH-3 (CV disease), TRIUMPH-4 (knee osteoarthritis) test effects in patients more likely to need treatment.
- Subgroup precision — larger numbers support meaningful analyses by demographic and clinical subgroup.
Frequently asked questions#
How much weight do people lose on retatrutide?
In the Phase 2 obesity trial, participants on the highest 12 mg dose lost an average of 24.2% of body weight over 48 weeks. The 8 mg dose produced about 22.8%, the 4 mg dose about 17.1%, and the 1 mg dose about 8.7%. Placebo participants lost approximately 2.1%.
How long does it take to plateau on retatrutide?
Phase 2 weight-loss curves were still trending downward at the 48-week endpoint, suggesting the plateau had not yet been reached. By contrast, semaglutide and tirzepatide curves typically begin to plateau around weeks 60–72. Phase 3 trials, which run longer, will determine retatrutide's true plateau.
Do all retatrutide patients lose weight?
In Phase 2, more than 90% of participants on the higher doses achieved at least 5% weight loss. Roughly 75% of those on the 12 mg dose achieved at least 15% weight loss, and about 26% achieved at least 25%. There were a small number of low responders, as with all GLP-1-class drugs.
Is retatrutide weight loss similar to bariatric surgery?
The headline number — about 24% average weight loss in Phase 2 — is in the same range as some bariatric procedures, particularly sleeve gastrectomy. That comparison should be read carefully: surgical weight loss is durable for years, while pharmacological weight loss reverses if the drug is discontinued.
Sources
Primary sources cited on this page
- Jastreboff AM, Kaplan LM, Frías JP, et al.. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023. Source ↗
- Jastreboff AM, Aronne LJ, Ahmad NN, et al.. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022. Source ↗
- Wilding JPH, Batterham RL, Calanna S, et al.. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021. Source ↗
Continue exploring
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GI events, heart-rate signal, and how withdrawals compared with placebo.
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