RESULTS FILE
Retatrutide Results in the Clinical Trials
What Phase 1b, Phase 2 obesity, Phase 2 diabetes, and the MASLD substudy each measured — and what the systematic reviews found when they compared retatrutide against the field.
The short version
Retatrutide results in clinical trials are among the largest published for any anti-obesity or metabolic agent. In a 48-week Phase 2 study in people with obesity, the highest dose studied produced an average 24.2% reduction in body weight. In a substudy focused on people with fatty liver disease (MASLD — metabolic dysfunction-associated steatotic liver disease, formerly called NAFLD), the same dose reduced liver fat by 82.4% at 24 weeks, with most participants reaching normal liver-fat levels.
These are measured outcomes in controlled clinical trials — not projections and not marketing. The drug is not approved. The trials are the full extent of what is documented about retatrutide results. This page reads those results systematically: what was measured, in whom, over how long, and what the comparisons to other agents look like — with every figure cited to its source.
For context on what these results mean for safety and what remains unknown, see Retatrutide effects.
Phase 2 obesity trial results: the headline figures
The Phase 2 obesity trial enrolled 338 adults with a BMI of at least 30 — or 27 to <30 with a weight-related comorbidity — and randomized them to 1, 4, 8, or 12 mg of retatrutide once weekly, or placebo, for 48 weeks [1].
Mean body-weight change at 48 weeks by dose:
- Placebo: -2.1%
- 1 mg: -8.7%
- 4 mg: -17.3%
- 8 mg: -22.8%
- 12 mg: -24.2%
The dose-response is monotonic — larger doses produced larger weight reductions at each step. All active doses significantly exceeded placebo.
A 2025 systematic review across 26 RCTs (15,491 participants without diabetes) found retatrutide 12 mg produced the largest single weight-loss estimate among all agents reviewed at 48 weeks: 22.1% (95% CI 19.3%-24.9%), ahead of tirzepatide 15 mg (up to 17.8%) and semaglutide 2.4 mg (up to 13.9%) [9]. The comparison is descriptive — no head-to-head trial has been conducted and cross-trial heterogeneity prevented pooled meta-analysis.
A 2025 review also documented the class-level challenge of weight rebound after discontinuation: retatrutide's durability off-treatment has not been studied in published data [10].
MASLD liver-fat results: the numbers this site is built around
The MASLD Phase 2a substudy is the retatrutide results that define this site's lens. Ninety-eight participants with obesity or overweight and MASLD (liver fat of at least 10% on MRI-PDFF, no type 2 diabetes) were enrolled and followed for 48 weeks [5].
Relative liver-fat change (MRI-PDFF) at 24 weeks:
- Placebo: +0.3%
- 1 mg: -42.9%
- 4 mg: -57.0%
- 8 mg: -81.4%
- 12 mg: -82.4%
At the 12 mg dose, 86% of participants reached normal liver fat (<5%) at 24 weeks. By 48 weeks, the 12 mg reduction was -86.0%.
A 2024 systematic review confirmed retatrutide produced the largest placebo-subtracted liver-fat reduction (81% on MRI-PDFF) among pharmacological agents reviewed — versus semaglutide at 41% and tirzepatide at 47% [7].
A meta-analysis of 25 RCTs (n=2,600) across GLP-1-based therapies found retatrutide displaying the most pronounced liver-fat reduction among agents evaluated, with significant reductions in ALT, AST, and GGT (liver-enzyme markers reflecting hepatic stress) [8].
A 2025 preclinical study in an accelerated mouse model of diet-induced steatohepatitis — designed to mirror human MASH (metabolic dysfunction-associated steatohepatitis, the more severe, inflammatory form of MASLD) — found significant reductions in ALT, hepatic triglycerides, hepatic cholesterol, and inflammatory markers, with a hepatic gene expression profile correlating to human disease [13].
For the mechanistic basis of the liver-fat effect, see how does retatrutide work.
Phase 2 type 2 diabetes results
The Phase 2 type 2 diabetes trial enrolled 281 adults and studied dose-escalating regimens from 0.5 to 12 mg once weekly for 36 weeks [2].
Key efficacy outcomes at 12 mg (primary timepoints):
- HbA1c change at 24 weeks: -2.02% (retatrutide) vs -0.01% (placebo)
- Body-weight change at 36 weeks: -16.94% (retatrutide) vs -3.00% (placebo)
- No severe hypoglycemia, no deaths
A 2026 overview of the full diabetes dataset reported efficacy figures including up to 2.16% HbA1c reduction and up to 26.56% weight loss across the studied populations, with GI event rates linked to escalation rate and starting dose [12]. A 2026 review of MASLD treatment in the context of type 2 diabetes characterized retatrutide as showing marked liver-fat reduction and MASH benefit signals in the diabetic population as well [15].
Phase 1b pharmacokinetics and early weight results
The first-in-human Phase 1b study enrolled 72 adults with type 2 diabetes (HbA1c 7.0-10.5%) and studied once-weekly subcutaneous retatrutide at 0.5, 1.5, 3, 3/6, and 3/6/9/12 mg over 12 weeks [4].
Half-life: approximately 6 days. Weight loss at the highest-dose cohort: -8.96 kg placebo-adjusted (90% CI -11.16 to -6.75) over 12 weeks. Daily glucose fell by 2.8 mmol/L at 3 mg. Treatment-emergent adverse events occurred in 63%, mostly GI and mostly mild.
The 6-day half-life supports once-weekly dosing and was consistent across all dose cohorts — confirming the pharmacokinetic target set by the C20 fatty-diacid acylation was achieved.
Systematic review comparisons: retatrutide vs the field
Several 2024-2025 systematic reviews place retatrutide results in the context of the broader incretin landscape without head-to-head trials.
Weight loss (adults without diabetes): A 2025 network analysis of 26 RCTs (n=15,491) found retatrutide 12 mg reported the largest weight-loss estimate (22.1%, 95% CI 19.3%-24.9% at 48 weeks) [9]. The investigators noted that cross-trial heterogeneity prevented pooled meta-analysis and that retatrutide was the only investigational agent in the review — all others had been approved.
Liver-fat reduction: A 2025 systematic review of double-blind RCTs found retatrutide's 81% placebo-subtracted MRI-PDFF reduction was the largest documented — versus semaglutide 41%, tirzepatide 47% [7]. A meta-analysis of 25 RCTs in GLP-1-based therapies found overall liver fat content fell 5.21% across the pooled population, with retatrutide displaying the most pronounced individual agent reduction [8].
Weight loss (overview): A 2025 review characterized retatrutide's up-to-24% weight loss as a step-change versus prior incretin therapies — specifically noting the glucagon-receptor component as the mechanistic addition that distinguishes it from dual GLP-1/GIP approaches [6].
None of these comparisons are head-to-head. Retatrutide remains investigational; all comparators in these reviews are approved drugs with long post-market safety records.