# Retatrutide Research: Phase 1b, Phase 2, and Phase 3 Trial Record

> Retatrutide Phase 1b pharmacokinetics, Phase 2 obesity and diabetes outcomes, MASLD findings, and the TRIUMPH Phase 3 program. Every figure cited to its primary source.

Phase 1b pharmacokinetics. Phase 2 results in obesity, type 2 diabetes, and MASLD. The TRIUMPH Phase 3 program and what it is designed to determine. Primary sources throughout.

## A plain-English map of the Retatrutide research record

Retatrutide (also called LY3437943) is a synthetic drug candidate being developed by Eli Lilly. It is being tested in humans in clinical trials — structured studies where participants receive the drug or a placebo under medical supervision. No trial has finished yet; the Phase 3 trials are ongoing.

Here is what has been published so far: a first-in-human Phase 1 study (NCT04143802) established that the drug was safe enough to study further [7]. A Phase 1b study in people with type 2 diabetes established that it has about a 6-day half-life — meaning it clears slowly enough to take once a week — and produced real reductions in weight and blood sugar [4]. Then came Phase 2 trials in three separate groups: people with obesity (no diabetes), people with type 2 diabetes, and people with fatty liver disease linked to metabolic factors. Those Phase 2 results are the most-cited data on this page.

Now Phase 3 — larger, longer trials — is underway. Until those finish and regulators review the results, retatrutide is investigational. It is not approved and not available as a medicine.

## Phase 1: First-in-human and pharmacokinetics

**NCT04143802 — First-in-human Phase 1.** Eli Lilly's initial study of LY3437943 in healthy participants established the compound's initial safety, tolerability, and pharmacokinetics via single and multiple ascending doses administered subcutaneously (injected into the fatty layer beneath the skin) [7]. This trial opened in 2019.

**Phase 1b — LY3437943 in type 2 diabetes.** 72 adults with type 2 diabetes (HbA1c 7.0–10.5%) received subcutaneous doses of 0.5 mg, 1.5 mg, 3 mg, or escalating regimens up to 3/6/9/12 mg once weekly over 12 weeks [4]. Key findings:
- Half-life: approximately 6 days — the pharmacokinetic property that supports once-weekly dosing.
- Placebo-adjusted weight change: -8.96 kg (90% CI: -11.16 to -6.75 kg) at the highest dose group.
- Daily glucose reduction: -2.8 mmol/L at 3 mg.
- Treatment-emergent adverse events in 63% of participants, mostly gastrointestinal; the safety profile was characterized as acceptable.

The 6-day half-life is the central pharmacokinetic datum for this site's lens. A half-life of ~6 days means that after one weekly injection, plasma concentration remains above its trough for approximately 4–5 days before the next dose, producing a relatively stable exposure profile with once-weekly dosing. For a full pharmacokinetic analysis, see [retatrutide half life](/half-life).

## Phase 2: Obesity (48-week) — the primary efficacy dataset

Jastreboff AM et al., *New England Journal of Medicine*, 2023 [1]. 338 adults with obesity (BMI ≥30 or ≥27 with comorbidity); 51.8% men; 48-week double-blind placebo-controlled trial. Subcutaneous once weekly at 1, 4, 8, or 12 mg.

**Retatrutide results by dose:**

| Dose | Mean body-weight change at 48 weeks |
|---|---|
| 1 mg | -1.6% |
| 4 mg | -8.7% |
| 8 mg | -17.3% |
| 12 mg | -24.2% |
| Placebo | -2.1% |

At 12 mg, 26% of participants lost ≥25% of body weight. Weight loss at 48 weeks was still trending downward — the trajectory had not plateaued.

Gastrointestinal adverse events were the most common: nausea (45% at 12 mg), diarrhea, vomiting, constipation. These were dose-related and predominantly mild to moderate. The discontinuation rate at 12 mg was 18%, driven primarily by GI adverse events. A dose-dependent heart-rate increase was observed, peaking around week 24.

**Retatrutide vs tirzepatide — what the Phase 2 data show.** Tirzepatide is a dual GIP/GLP-1 receptor agonist (not a triple agonist; it does not include glucagon). The approved highest dose of tirzepatide in obesity trials produced a mean weight reduction of approximately 20–22% over 72 weeks in the SURMOUNT-1 trial. Retatrutide's 12 mg produced 24.2% over 48 weeks — a shorter trial, in a different population, with different baseline characteristics. A direct comparison cannot be drawn from these separate Phase 2 datasets. An active-comparator Phase 3 trial (NCT06662383) is specifically designed to answer this question [11].

## Phase 2: Type 2 diabetes and MASLD

**Type 2 diabetes** — Rosenstock J et al., *The Lancet*, 2023 [2]. 281 adults with T2D on stable background therapy; 36 weeks. Doses 0.5–12 mg once weekly with step escalation. At 12 mg: HbA1c -2.02 percentage points vs -0.01 for placebo at 24 weeks; body weight -16.94% vs -3.00% placebo at 36 weeks. No severe hypoglycemia and no deaths were recorded. A 2026 expert review summarizing accumulated dosing data noted HbA1c reductions up to 2.16% across dose groups [15].

**MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)** — Sanyal AJ et al., *Nature Medicine*, 2024 [5]. 98 participants with obesity or overweight plus MASLD (≥10% liver fat by MRI-PDFF), no T2D. Subcutaneous once weekly at 1, 4, 8, or 12 mg; 48 weeks.

Relative liver-fat change at 24 weeks: -42.9% (1 mg) / -57.0% (4 mg) / -81.4% (8 mg) / -82.4% (12 mg) versus +0.3% with placebo. At 12 mg, 86% of participants reached normal liver fat (defined as <5% by MRI-PDFF). Reductions were sustained at 48 weeks (-86.0% at 12 mg). These are the most striking liver-fat results yet reported for any pharmacological agent in a placebo-controlled trial.

## Phase 3: The TRIUMPH program and ongoing trials

Retatrutide is in Phase 3. The TRIUMPH program and concurrent trials are ongoing as of mid-2026; results have not been published.

- **TRIUMPH-2 (NCT05931367)** — Obesity with type 2 diabetes [8].
- **TRIUMPH-3 (NCT05882045)** — Obesity with cardiovascular disease [9].
- **NCT06383390** — Cardiovascular outcomes and kidney function [10].
- **NCT06662383** — Active-comparator Phase 3 vs tirzepatide [11].

The cardiovascular and kidney outcome trials are specifically designed to address the questions that Phase 2 cannot answer — long-term organ-level safety and durability. A separate chronic kidney disease outcomes study (TRANSCEND-CKD) is also examining renal effects. No pivotal data from any of these trials had been published as of the date of this digest.

A 2025 review by Katsi V et al. in *Biomolecules* provides the most current narrative synthesis of retatrutide's mechanism and Phase 1/2 record [6]. A 2024 review in *Cell* places triple agonism in the broader context of obesity pharmacotherapy and bariatric surgery comparability [13]. A 2024 review in *npj Metabolic Health and Disease* situates retatrutide within the broader incretin-class landscape for cardiometabolic disease [12].

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A methodical reading of the published retatrutide trial record — Phase 1b pharmacokinetics through Phase 3 program, every figure walked to its source and the investigational status held in plain view; not a clinic, not a telehealth service, and nothing here dispensed or prescribed.