# Retatrutide Results in the Clinical Trials — Phase 2 Endpoints Appraised

> Retatrutide results from Phase 2 obesity, MASLD, and type 2 diabetes trials — body-weight change, liver-fat reduction, HbA1c data, and comparative efficacy from systematic reviews.

Phase 2 endpoints from obesity, type 2 diabetes, and MASLD liver-fat trials — logged to source.

## The brief version

The retatrutide results that have attracted the most attention come from three Phase 2 trials. In adults with obesity, the highest dose produced an average weight loss of 24.2% over 48 weeks. In adults with MASLD (fatty liver disease), 86% reached normal liver fat levels by week 24 — a finding specific to this site's liver-MASLD lens. In adults with type 2 diabetes, blood-sugar control (HbA1c) improved by over 2 percentage points.

These are not the results of an approved drug. Retatrutide is investigational — in Phase 3 trials as of 2026, not yet on the market. The figures below are published Phase 2 endpoints, logged with their citations. Phase 3 is running to confirm, extend, and qualify these findings in larger populations and longer follow-up.

## Obesity Phase 2 results

Trial: Jastreboff AM, et al., *NEJM* 2023, 48 weeks, 338 adults with obesity (BMI ≥30 or ≥27 with comorbidity) [1].

| Dose | Body-weight change at 48 weeks |
|---|---|
| Placebo | −2.1% |
| 1 mg | dose-dependent reduction |
| 4 mg | dose-dependent reduction |
| 8 mg | dose-dependent reduction |
| 12 mg | **−24.2%** |

GI adverse events (nausea, diarrhea, vomiting, constipation) were the most common adverse events and were dose-related, mostly mild-to-moderate. Discontinuation rate at 12 mg: 18%, predominantly GI-driven. Heart rate increased in a dose-dependent manner, peaking at approximately 24 weeks.

The 12 mg result was the largest mean body-weight reduction reported in a Phase 2 obesity trial at the time of publication. It established retatrutide as a compound warranting Phase 3 investigation.

## MASLD liver-fat results

Trial: Sanyal AJ, et al., *Nature Medicine* 2024, 48 weeks, 98 participants with obesity/overweight and MASLD (≥10% liver fat by MRI-PDFF, no T2D) [5].

Relative liver-fat change at 24 weeks by dose:

| Dose | MRI-PDFF change at 24 weeks | Normal liver fat (\<5%) reached |
|---|---|---|
| Placebo | +0.3% | — |
| 1 mg | −42.9% | — |
| 4 mg | −57.0% | — |
| 8 mg | −81.4% | — |
| 12 mg | **−82.4%** | **86%** |

At 48 weeks, the 12 mg group showed −86.0% liver-fat change — reduction sustained and deepened. ALT (alanine aminotransferase — a liver enzyme elevated when the liver is inflamed or damaged) also declined significantly.

This is the finding most central to this dossier's liver-MASLD lens. The glucagon receptor arm of retatrutide drives this result via hepatic lipolysis (breakdown of stored liver fat) and mitochondrial fat oxidation — mechanisms distinct from GLP-1–only agents that reduce liver fat primarily through weight loss and caloric restriction [7].

A 2026 network meta-analysis confirmed the finding at the class level: glucagon receptor agonists including retatrutide showed MRI-PDFF mean difference of −46.09 and ALT mean difference of −22.10, with significant ELF fibrosis score reduction, versus placebo [12].

## Type 2 diabetes Phase 2 results

Trial: Rosenstock J, et al., *Lancet* 2023, 36 weeks, 281 adults with type 2 diabetes [2].

- **HbA1c at 24 weeks:** −2.02 percentage points (12 mg) versus −0.01 (placebo)
- **Body weight at 36 weeks:** −16.94% (12 mg) versus −3.00% (placebo)
- **GI adverse events:** mild-to-moderate in 35% of participants
- **Severe hypoglycemia:** none observed
- **Deaths:** none

Participants on background insulin required dose-reduction to avoid hypoglycemia — the GLP-1/GIP agonism of retatrutide augments insulin secretion, which combines with exogenous insulin to lower blood glucose.

## Comparative context

A 2025 systematic review (Moiz et al., *Annals of Internal Medicine*, 26 RCTs, 15,491 adults without diabetes) placed retatrutide 12 mg at 22.1% weight loss (95% CI 19.3%–24.9%) at 48 weeks in the same evidence landscape as tirzepatide 15 mg at 17.8% at 72 weeks and semaglutide 2.4 mg at 13.9% at 68 weeks [9]. The comparison is descriptive — trial populations, durations, and baseline characteristics differ; no meta-analysis was performed.

A 2026 network meta-analysis (Abulehia et al.) ranked retatrutide highest for weight and HbA1c reduction versus placebo among glucagon receptor agonists in the network — the only agent whose HbA1c effect reached significance; survodutide ranked second [14].

The 2025 Biomolecules review (Katsi et al.) characterized the up-to ~24% weight loss across retatrutide Phase 1/2 trials as a step-change versus prior incretin therapies [6].

See [how does retatrutide work](/how-it-works) for the mechanistic explanation of why three-receptor agonism produces larger effects, and [Retatrutide research](/research) for the full evidence review.

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An independent appraisal of the published retatrutide trial record — each figure traced to its study, the Phase 3 questions held open, nothing here prescribed or dispensed.