# Retatrutide Results in the Clinical Trials

> Retatrutide results across Phase 1–3 trials: 24.2% mean weight loss at 48 weeks, HbA1c reductions in T2D, liver fat findings in MASLD, and Phase 3 TRANSCEND and TRIUMPH data.

A quantitative summary of every published efficacy endpoint: body weight, HbA1c, liver fat, and safety — with each number referenced to its source.

## Before the numbers

Retatrutide results from clinical trials have drawn attention across the medical community because the weight-loss figures are the largest reported for any drug in Phase 2 trials of comparable length. In a 48-week Phase 2 obesity study, participants at the highest tested amount lost an average of 24.2% of their body weight, compared to 2.1% with placebo [1]. That is roughly three to four times the weight loss of previous single-target weight-loss medicines.

This page collects the published efficacy numbers from every completed retatrutide trial — Phase 1b, Phase 2 obesity, Phase 2 type 2 diabetes, Phase 2 MASLD (liver fat), and the first Phase 3 results. Every number has a citation. Numbers are study averages, not individual outcomes — variation between people in trials is wide, and real-world results in non-trial settings cannot be predicted from trial data.

## Phase 1b results: weight and glucose

**Trial:** Urva S et al., Lancet 2022 (n=72 adults with T2D, 12 weeks) [4]

- Placebo-adjusted weight change at highest dose cohort: **−8.96 kg** (90% CI: −11.16 to −6.75)
- Daily glucose reduction at 3 mg: **−2.8 mmol/L**
- Half-life established: **approximately 6 days**
- Treatment-emergent adverse events: 63% of participants, predominantly gastrointestinal
- Safety profile: characterized as acceptable for Phase 2 development

These early results from 12 weeks signaled efficacy that was substantially larger than Phase 1b data from predecessor compounds in the same receptor class.

## Phase 2 obesity trial results

**Trial:** Jastreboff AM et al., N Engl J Med 2023 (n=338 adults with obesity, 48 weeks) [1]

**Primary endpoint — mean body-weight change at 48 weeks:**
- 1 mg: **−8.7%**
- 4 mg: **−17.3%**
- 8 mg: **−22.8%**
- 12 mg: **−24.2%**
- Placebo: **−2.1%**

**Secondary endpoints:**
- BMI reduction at 12 mg: proportional to weight change
- Waist circumference reduction: significant and dose-graded
- No plateau in the weight-loss curve at 48 weeks (loss still ongoing at trial end at 12 mg)

**Safety:**
- GI adverse events (nausea, diarrhea, vomiting, constipation): dose-related; nausea up to 45% at 12 mg
- Discontinuation due to adverse events: 18% at 12 mg
- Dose-dependent heart-rate increase: peaking around 24 weeks
- No severe hypoglycemia

A pooled systematic review (Misra et al. 2025, n=691 from 3 RCTs) confirmed the 12 mg dose as maximally effective across weight, BMI, and waist circumference endpoints [7].

## Phase 2 type 2 diabetes results

**Trial:** Rosenstock J et al., Lancet 2023 (n=281 adults with T2D, 36 weeks) [2]

**Primary endpoint — HbA1c change at 24 weeks (12 mg vs placebo):**
- 12 mg: **−2.02%**
- Placebo: **−0.01%**

**Body weight at 36 weeks (12 mg vs placebo):**
- 12 mg: **−16.94%**
- Placebo: **−3.00%**

**Safety:**
- Mild-to-moderate GI adverse events: 35% of participants
- No severe hypoglycemia
- No deaths

The simultaneous HbA1c and weight reduction in a T2D population — with no severe hypoglycemia — established the safety profile needed for Phase 3 development in this indication.

## Phase 2 MASLD liver-fat results

**Trial:** Sanyal AJ et al., Nature Medicine 2024 (n=98 adults with obesity/overweight and MASLD, 48 weeks) [5]

**Relative liver-fat change at 24 weeks (MRI-PDFF):**
- 1 mg: **−42.9%**
- 4 mg: **−57.0%**
- 8 mg: **−81.4%**
- 12 mg: **−82.4%**
- Placebo: **+0.3%**

**Liver fat normalization (reaching <5% liver fat):**
- 12 mg: **86% of participants** at 24 weeks

**Sustained reductions at 48 weeks:**
- 12 mg: **−86.0%** (further improvement from 24-week mark)

These are the largest pharmacologically produced liver-fat reductions reported in any published randomized trial. MASLD (metabolic dysfunction-associated steatotic liver disease — formerly non-alcoholic fatty liver disease) is a common comorbidity of obesity with no previously approved pharmacological treatment with effects of this magnitude.

## Phase 3 results: TRANSCEND-T2D-1

**Trial:** Bajaj HS et al., Lancet 2026 (n=537 adults with T2D on diet/exercise only, 40 weeks) [12]

**Primary endpoint — HbA1c change at 40 weeks (12 mg vs placebo):**
- 12 mg: **−1.94%**
- Placebo: **−0.81%**

**Body weight change:**
- 12 mg: **−15.3%**
- Placebo: **−2.6%**

**Safety:**
- Adverse events predominantly mild-to-moderate GI
- No severe hypoglycemia
- Discontinuation due to adverse events: 9.8% retatrutide vs 2.2% placebo

This is the first Phase 3 retatrutide trial to publish results. The TRIUMPH-1, -2, and -3 trials (obesity, obesity+T2D, obesity+CVD) are ongoing [9, 10, 11].

## Cardiovascular risk factor findings

A 2024 conference abstract presented at the ACC (Kommu S et al., J Am Coll Cardiol 2024) reported retatrutide-associated improvements in lipid and cardiovascular risk factors alongside weight loss [8]. Full numeric results were not yet published in peer-reviewed form as of mid-2026. Dedicated cardiovascular outcomes trials are registered and ongoing; their results will be required before the full cardiovascular risk-benefit profile is known.

For summary comparison across the incretin polyagonist class: a 2026 meta-analysis (Chan ZH et al.) found the class as a whole significantly reduced body weight, waist circumference, HbA1c, and fasting glucose versus placebo [13].

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A digest of the published trial record — not a clinic, not a formulary, and not a prescription.