# Retatrutide Results in the Clinical Trials

> Retatrutide results across Phase 1b, Phase 2 obesity and diabetes trials, the MASLD substudy, and the Phase 3 TRANSCEND-T2D-1 readout. Every figure cited.

A trial-by-trial breakdown of the published efficacy data — weight, glucose, liver fat, pharmacokinetics. Every figure cited to its source.

## The brief version on results

Retatrutide results from Phase 2 and Phase 3 trials are the reason this compound has attracted more clinical-development attention than any other investigational injectable compound in the obesity space. In Phase 2, it produced weight losses of up to -24.2% in 48 weeks [1] — a number that exceeds every prior approved once-weekly injectable in controlled trials. It cut liver fat by over 80% in fatty liver disease [5] and lowered blood sugar substantially in type 2 diabetes [2].

The first Phase 3 data confirmed the Phase 2 picture at larger scale and longer follow-up in a diabetes population [12]. Multiple outcome trials — for heart disease, kidney disease, and active comparison versus tirzepatide — are still running.

All the numbers are below, organized by trial. Retatrutide is not approved; these results are from controlled clinical studies, not commercial use.

## Phase 1b results: pharmacokinetics and early weight loss

**Trial:** Phase 1b, multiple-ascending-dose (MAD), n=72 adults with type 2 diabetes, 12 weeks [4].

**Primary finding:** Half-life approximately 6 days, supporting once-weekly dosing. This PK result was the pharmacokinetic proof-of-concept for the entire weekly-dosing strategy.

**Weight loss (placebo-adjusted):** At the highest dose group, -8.96 kg over 12 weeks (90% CI -11.16 to -6.75 kg).

**Glucose:** Daily glucose reduced by -2.8 mmol/L at 3 mg.

**Safety:** Treatment-emergent adverse events in 63%, predominantly GI, mostly mild. No serious adverse events related to the compound. Acceptable safety profile confirmed for Phase 2 entry.

## Phase 2 obesity results: -24.2% body weight at 48 weeks

**Trial:** Phase 2, randomized double-blind placebo-controlled, n=338 adults with obesity or overweight with comorbidity, 48 weeks, published NEJM 2023 [1].

**Primary endpoint — mean body-weight change at 48 weeks:**

| Dose | Mean weight change | vs Placebo (-2.1%) |
|------|-------------------|--------------------|
| 1 mg | -3.7% | -1.6 pp |
| 4 mg | -8.7% | -6.6 pp |
| 8 mg | -17.3% | -15.2 pp |
| 12 mg | -24.2% | -22.1 pp |

**Responder analysis at 12 mg:**
- ≥5% weight loss: 100% of completers
- ≥10% weight loss: 91%
- ≥20% weight loss: 75%
- ≥30% weight loss: 26%

**Adverse events:**
- GI events (nausea, diarrhea, vomiting, constipation): dose-related, mostly mild to moderate
- Discontinuation due to AEs at 12 mg: 18%
- Dose-dependent resting heart rate increase peaking at week 24: mean +5–7 bpm at highest doses
- Injection-site reactions: ~8%

## Phase 2 type 2 diabetes results: HbA1c -2.02%, weight -16.94%

**Trial:** Phase 2, randomized double-blind placebo and active-controlled, n=281 adults with type 2 diabetes, 36 weeks, published The Lancet 2023 [2].

**Glycemic endpoint — HbA1c change at 24 weeks:**
- 12 mg: -2.02% vs -0.01% placebo
- 8 mg: -1.83%

**Weight endpoint at 36 weeks:**
- 12 mg: -16.94% vs -3.00% placebo

**Safety:** Mild-to-moderate GI adverse events in 35%. No severe hypoglycemia in participants not on background insulin. No deaths. This trial confirmed the mechanism's dual glycemic-plus-weight profile is reproducible in a diabetes population.

## Phase 2 MASLD results: liver fat -82.4% at 24 weeks

**Trial:** Phase 2a, randomized, n=98 adults with obesity/overweight and MASLD (≥10% liver fat by MRI-PDFF, no type 2 diabetes), 48 weeks, published Nature Medicine 2024 [5].

**Liver fat change at 24 weeks (relative to baseline by MRI-PDFF):**
- 12 mg: -82.4%
- 8 mg: -81.4%
- 4 mg: -57.0%
- 1 mg: -42.9%
- Placebo: +0.3%

**Responders reaching normal liver fat (<5%) at 12 mg:** 86%

**Sustained to 48 weeks:** -86.0% relative reduction at 12 mg.

This is the most striking single-endpoint result in the retatrutide dataset. The glucagon receptor arm's direct hepatic lipid metabolism effect, additive to weight-loss-driven fat clearance, accounts for the depth of the response — a mechanism absent from pure GLP-1 agents.

## Phase 3 TRANSCEND-T2D-1 results: first Phase 3 readout (2026)

**Trial:** Phase 3, randomized double-blind placebo-controlled, n=537 adults with type 2 diabetes, 40 weeks, published The Lancet 2026 [12].

**Primary endpoint — HbA1c reduction at 40 weeks:**
- 12 mg: -1.94% vs -0.81% placebo

**Secondary endpoint — body weight change:**
- 12 mg: -15.3% vs -2.6% placebo

**Safety:**
- Discontinuation due to AEs: 8.5% at 12 mg vs 2.2% placebo
- No severe hypoglycemia
- Adverse events: predominantly mild-to-moderate GI

This is the first Phase 3 data for retatrutide. It confirms Phase 2 efficacy at Phase 3 scale in a diabetes population. TRIUMPH obesity trials and cardiovascular/kidney outcomes trials remain ongoing.

## What the retatrutide results mean in context

The -24.2% weight loss at 48 weeks in Phase 2 is the headline. For comparison, the most efficacious approved once-weekly injectable compounds produced approximately 20–22% weight loss in their Phase 3 pivotal trials at highest doses. Retatrutide's Phase 2 data exceed that; Phase 3 obesity data are still pending.

The 86% normal-liver-fat responder rate at 12 mg in MASLD is equally striking — liver fat below 5% is the diagnostic threshold for normal liver, and clearing that in 86% of trial participants at 24 weeks is a result with no near precedent in the pharmacological literature.

A 2025 expert review of the obesity pipeline concluded that retatrutide achieves weight reduction currently unmatched by any approved oral or injectable agent and characterized it as approaching bariatric surgery outcomes [8]. A 2026 review identified weight regain on discontinuation as the class-level limitation shared with other GLP-1-based therapies — not yet studied specifically for retatrutide long-term [14].

All these figures are from controlled trials under clinical supervision. [Retatrutide results](/results) in a research-labeled, unmonitored context cannot be assumed to replicate these numbers.

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An independent briefing on published investigational trial data — not a clinic, not a formulary, not a recommendation.