# Retatrutide Results in the Clinical Trials — Research Digest

> Retatrutide results from Phase 2 obesity, diabetes, and MASLD trials: −24.2% body weight, −82.4% liver fat, −2.02% HbA1c. Every figure cited to its published source.

Every published efficacy and safety number — Phase 1 through Phase 2 — with the trial it came from and the caveat it carries.

## The summary in plain numbers

Retatrutide results from the Phase 2 program: −24.2 percent mean body-weight reduction at 48 weeks (12 mg, obesity trial) [1], −16.94 percent body-weight reduction at 36 weeks (12 mg, type 2 diabetes trial) [2], −82.4 percent relative liver-fat reduction at 24 weeks (12 mg, MASLD substudy) [5], −2.02 percent HbA1c (blood-sugar marker) reduction at 24 weeks (12 mg, diabetes trial) [2]. These are the published Phase 2 results — impressive on their face and, by a 2025 Biomolecules review's characterization, a step-change versus prior incretin therapies [6]. Phase 3 results from the TRIUMPH program are not yet published; retatrutide remains investigational and unapproved. Every number below comes with a trial ID and a citation.

## Phase 2 obesity trial results (48 weeks)

Trial: published in the New England Journal of Medicine, 2023. N = 338 adults with obesity. Doses: 1, 4, 8, 12 mg once weekly subcutaneous for 48 weeks versus placebo [1].

Mean body-weight change at 48 weeks:
- 1 mg: −8.7 percent
- 4 mg: −17.3 percent
- 8 mg: −22.8 percent
- 12 mg: −24.2 percent
- Placebo: −2.1 percent [1]

Safety highlights: gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation) were the most common and were dose-related. Discontinuation due to adverse events: 18 percent at 12 mg. Dose-dependent heart-rate increase: mean approximately 5–7 bpm at the highest dose, peaking around week 24. No severe hypoglycemia. No deaths [1].

A 2025 Biomolecules review characterizes the −24.2 percent at 48 weeks as the largest body-weight reduction reported for a pharmacological agent at a comparable trial stage, attributing the additional effect beyond dual agonists to glucagon-receptor-driven thermogenesis [6]. The 2026 IUPHAR review of glucagon receptor agonism in obesity notes that durability of this effect after discontinuation has not been confirmed in long-term data [13].

## Phase 2 type 2 diabetes trial results (36 weeks)

Trial: published in The Lancet, 2023. N = 281 adults with type 2 diabetes on background medication. Doses: stepwise escalation to 1, 4, 8, 12 mg once weekly subcutaneous for 36 weeks [2].

Key outcomes at 12 mg:
- HbA1c change at 24 weeks: −2.02 percent (12 mg) versus −0.01 percent (placebo)
- Body-weight change at 36 weeks: −16.94 percent (12 mg) versus −3.00 percent (placebo)
- GI adverse events: mild-to-moderate in 35 percent of participants
- Severe hypoglycemia: zero
- Deaths: zero [2]

The 2026 TRANSCEND-T2D-1 Phase 3 trial confirmed the diabetes results: retatrutide significantly improved glycemic control and body weight as monotherapy in type 2 diabetes, with a predominantly mild-to-moderate adverse event profile and no severe hypoglycemia — consistent with the Phase 2 signal [12].

## Phase 2 MASLD substudy results (48 weeks)

Trial: published in Nature Medicine, 2024. N = 98 participants with obesity or overweight and MASLD (≥10 percent liver fat by MRI-PDFF, no type 2 diabetes). Doses: 1, 4, 8, 12 mg once weekly for 48 weeks [5].

Relative liver-fat change at 24 weeks:
- 1 mg: −42.9 percent
- 4 mg: −57.0 percent
- 8 mg: −81.4 percent
- 12 mg: −82.4 percent
- Placebo: +0.3 percent [5]

At 12 mg, 86 percent of participants reached normal liver-fat content (<5 percent) by week 24, with reduction deepening to −86.0 percent at week 48 [5]. No type 2 diabetes was present in this cohort, confirming that the liver-fat effect is not entirely mediated through blood-sugar improvement alone.

## Phase 1b results (12 weeks)

Trial: published in The Lancet, 2022. N = 72 adults with type 2 diabetes in a multiple-ascending-dose design [4].

Key outcomes:
- Plasma half-life: approximately 6 days
- Placebo-adjusted weight loss at highest-dose cohort: −8.96 kg (90% CI −11.16 to −6.75) over 12 weeks
- Daily glucose reduction at 3 mg: −2.8 mmol/L
- Treatment-emergent adverse events: 63 percent, predominantly GI
- Safety profile: judged acceptable; program advanced to Phase 2 [4]

## Structural mechanism: what the cryo-EM shows

Published in Cell Discovery, 2024. Cryo-electron microscopy resolved retatrutide bound to GLP-1R, GIPR, and GCGR simultaneously at resolutions of 2.68, 3.26, and 2.84 Ångströms respectively [3]. Relative potency versus endogenous hormones: approximately 8.9x native GIP at GIPR, 0.4x native GLP-1 at GLP-1R, and 0.3x native glucagon at GCGR [3]. The structures explain why GIPR selectivity is highest — and provide the mechanistic confirmation that the weight-loss result is not a single-receptor effect. The 2024 Diabetes Care review by Drucker et al. highlights retatrutide's unique pharmacokinetic and pharmacodynamic profile as a basis for its distinct efficacy signal [15].

## Phase 3: what has not yet been measured

Phase 3 results from the TRIUMPH program are the critical missing data. TRIUMPH-1 (NCT05929066) — the pivotal obesity trial with thousands of participants — has not published primary outcomes [7]. TRIUMPH-3 (NCT05882045) — obesity with cardiovascular disease — is ongoing [8]. The cardiovascular and kidney outcomes trial (NCT06383390) and the head-to-head trial versus tirzepatide (NCT06662383) are both ongoing [9][10]. Until these trials report, the Phase 2 numbers above are the full published efficacy record. They are the most compelling investigational anti-obesity data in the current literature — and they are still Phase 2 data. Phase 3 may confirm, expand, or modify what Phase 2 measured.

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A broadsheet digest of the published clinical trial record — not a clinic, not a prescription service, not a vendor.