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LITERATURE REVIEW · PHASE 2 T2D RCT

Retatrutide Phase 2 (Diabetes)

Rosenstock et al., Lancet, 2023. 36-week randomised double-blind, placebo- and active-controlled Phase 2 trial of once-weekly Retatrutide in adults with type 2 diabetes on diet, exercise and metformin.

QUICK ANSWER
TL;DR

Quick answer

The Retatrutide Phase 2 diabetes trial was a 36-week randomised double-blind, placebo- and active-controlled Phase 2 trial of once-weekly Retatrutide (0.5, 4, 8 and 12 mg) versus placebo and dulaglutide 1.5 mg in 281 adults with type 2 diabetes on diet, exercise and metformin. Retatrutide produced dose-dependent HbA1c and body-weight reduction, with the highest doses exceeding dulaglutide 1.5 mg.
EXTENDED ANSWER
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Extended answer

What was the Retatrutide Phase 2 (Diabetes) trial?

The Retatrutide Phase 2 diabetes trial was a 36-week, randomised, double-blind, placebo- and active-controlled Phase 2 trial evaluating once-weekly subcutaneous Retatrutide at 0.5, 4, 8 and 12 mg maintenance doses versus placebo and versus once-weekly dulaglutide 1.5 mg (active reference) in adults with type 2 diabetes on diet, exercise and metformin. Published by Rosenstock and colleagues in the Lancet in 2023, the trial randomised 281 participants and reported dose-dependent HbA1c reduction and body-weight reduction with Retatrutide, with the higher doses exceeding both placebo and the dulaglutide 1.5 mg active reference. The trial is the reference Phase 2 dataset for the triple-agonist class in type 2 diabetes.
KEY FACTS

Key facts

Compound
Retatrutide 0.5/4/8/12 mg SC weekly
Design
Randomised, double-blind, placebo- and active-controlled, Phase 2
N
281
Population
Adults with T2D on diet, exercise and metformin
Duration
36 weeks
Primary outcome
Change in HbA1c from baseline
Journal
Lancet (2023)
DOI
10.1016/S0140-6736(23)01053-X
PMID
37364590

Background

The Retatrutide Phase 2 diabetes trial was designed to evaluate the triple GIP/GLP-1/glucagon receptor agonist in the type 2 diabetes population, alongside a placebo comparator and an active GLP-1 receptor agonist reference (dulaglutide 1.5 mg once weekly). [1]

Study design

Randomised, double-blind, placebo- and active-controlled, multi-arm parallel-group Phase 2 trial. Participants were randomised across Retatrutide 0.5, 4, 8 and 12 mg maintenance-dose arms, matching placebo and dulaglutide 1.5 mg, each administered subcutaneously once weekly for 36 weeks.

Population

281 adults with type 2 diabetes and HbA1c 7.0–10.5% on diet, exercise and stable metformin.

Intervention

Once-weekly subcutaneous Retatrutide titrated to 0.5, 4, 8 or 12 mg maintenance dose.

Comparator

Matching placebo and once-weekly subcutaneous dulaglutide 1.5 mg (active reference).

Primary endpoints

Mean change in HbA1c from baseline to week 24 and week 36 for each Retatrutide dose versus placebo.

Secondary endpoints

Change in body weight, proportions achieving HbA1c targets (<7%, <5.7%), fasting glucose, lipid parameters, and comparisons versus dulaglutide 1.5 mg.

Key findings

  • Dose-dependent HbA1c reduction was observed across Retatrutide arms, exceeding placebo at all doses and exceeding dulaglutide 1.5 mg at the higher doses.
  • Dose-dependent body-weight reduction was observed, exceeding both placebo and dulaglutide 1.5 mg at higher doses.
  • Gastrointestinal adverse events were the dominant tolerability finding and were dose-dependent.

Mechanistic significance

  • Consistent with the triple-agonist hypothesis that combined GIP/GLP-1/glucagon receptor engagement modulates both glycaemic and weight axes beyond mono- or dual-agonist references.
  • Provides the first randomised T2D dataset positioning Retatrutide against a mono-GLP-1 receptor agonist reference (dulaglutide 1.5 mg).

Limitations

Research limitations

  • Phase 2 trial; smaller sample size than Phase 3 SURPASS/STEP references.
  • 36-week duration is short relative to lifelong glycaemic management.
  • Dulaglutide 1.5 mg is not the maximum licensed dulaglutide dose (4.5 mg is licensed in some regions), which limits inference on GLP-1 receptor agonist head-to-head positioning.
  • Longer-term glycaemic, lipid and safety data require Phase 3 evaluation.

Research context

The Retatrutide Phase 2 diabetes trial is the T2D companion to the Retatrutide Phase 2 obesity trial and sits alongside SURPASS-2 (Tirzepatide vs Semaglutide) as reference material for cross-class incretin-agonist comparisons.

Research-use framing

This is an educational literature summary of a published clinical trial. Oxford Research Peptides supplies Retatrutide as a lyophilised reference standard for in-vitro laboratory research only. Nothing on this page is medical advice.
Related studies
Compound reference: Retatrutide monograph. Related guides: what is retatrutide, retatrutide mechanism of action, retatrutide research applications.

References1

  1. 1.

    Rosenstock J, Frías JP, Rodbard HW, et al.. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo- and active-controlled, parallel-group, Phase 2 trial.. Lancet. 2023;402(10401):529-544.

    DOI: 10.1016/S0140-6736(23)01053-XPMID: 37364590
EVIDENCE SUMMARY
Evidence

Evidence summary

Strong evidence
Research confidenceHigh confidence
Peer-reviewed Phase 2 randomised placebo- and active-controlled trial published in the Lancet (Rosenstock et al. 2023).
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EDITORIAL NOTICE

Research use only

All materials referenced are supplied strictly for in-vitro laboratory research. Not for human or animal consumption, diagnosis, or therapeutic use.
VERSION HISTORY
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Independent scientific review
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Publication information

Published
2026-11-01
Updated
2026-11-01
Reviewed
2026-11-01
Version
1.0

Revision history

  1. v1.02026-11-01· Editorial Team

    Research Literature Programme 1 — initial publication of dedicated STEP, SURPASS and Retatrutide Phase 2 trial summaries.

Editorial standards

Content is reviewed against our editorial process for scientific accuracy, sourcing, and clarity. Read our editorial standards.

Conflict of interest

Oxford Research Peptides supplies research-grade reference peptides commercially. Editorial pages are drafted and reviewed to describe published scientific literature accurately and do not recommend, promote or endorse any specific commercial product. Product mentions on educational pages are strictly for cross-referencing catalogue entries.

Next scheduled review: 2028-05-01. Our research methodology describes how the review is conducted.

Research use only

All materials referenced are supplied strictly for in-vitro laboratory research. Not for human or animal consumption, diagnosis, or therapeutic use.
Published: 2026-11-01Updated: 2026-11-01