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AMIRAVOResearch Library

Retatrutide vs mazdutide

Retatrutide and mazdutide both include glucagon-receptor agonism: retatrutide is a single peptide that activates GIP, GLP-1 and glucagon receptors, while mazdutide activates GLP-1 and glucagon receptors 1,2. Retatrutide is investigational, with phase 3 results published in 2026 3,4. Mazdutide was approved in China in 2025, but neither had a Drugs@FDA application record when queried on 24 October 2026 5,6,7. No trial comparing them directly was identified 8,9.

Unbranded reference vial illustrating Retatrutide; not an actual product
Retatrutide
Investigational
Unbranded reference vial illustrating Mazdutide; not an actual product
Mazdutide
Approved outside the US

Side by side

FieldRetatrutideMazdutide
ClassTriple GIP, GLP-1 and glucagon receptor agonist (investigational) 1Dual GLP-1 receptor and glucagon receptor agonist 2,5
Origin and structureSingle synthetic peptide with agonist activity at three receptors; in vitro it showed balanced glucagon and GLP-1 receptor activity and greater GIP receptor activity 10,11Long-acting synthetic analogue of oxyntomodulin with a fatty-acyl side chain to extend half-life 12
Proposed mechanismIn obese mice, glucagon-receptor-driven increases in energy expenditure added to GIP- and GLP-1-receptor-driven reductions in calorie intake 11Binds GLP-1 and glucagon receptors in vitro; in mice, body-weight reduction persisted in knockout animals lacking either receptor 12
Half-lifeAbout 6 days in a phase 1b multiple-ascending-dose study in type 2 diabetes 10150.9 to 403.5 hours in a phase 1b study in Chinese adults with overweight or obesity 12
Highest human trial phasePhase 3 (TRIUMPH-1, TRIUMPH-2, TRANSCEND-T2D-1 published) 3,4,13Phase 3 published; phase 4 studies registered in China 2,9,14
FDA statusNot approved; no Drugs@FDA application record as of 24 October 2026 6Not approved by the FDA (no Drugs@FDA record as of 24 October 2026) 7; approved in China in June and September 2025 5
Published human outcomesTRIUMPH-1 (2339 adults without diabetes): -17.6% to -25.0% vs -3.9% with placebo at 80 weeks, with lower knee-pain scores and apnea-hypopnea index in subgroups 3; TRIUMPH-2 (obesity with type 2 diabetes): -11.9% to -18.8% vs -5.1% 4GLORY-1: -11.00% and -14.01% vs +0.30% at 48 weeks 2; GLORY-2: -16.65% vs -1.50% at 60 weeks 14; HbA1c reductions vs placebo and dulaglutide in type 2 diabetes 15,16
Safety signalsMainly gastrointestinal; dose-dependent heart-rate increases that peaked at 24 weeks in phase 2 1; more hypotension and dysesthesia than placebo in TRIUMPH-2 4Mainly gastrointestinal; vomiting 53.1% vs 1.3% with placebo in GLORY-2 14; heart-rate increases and mild asymptomatic ECG findings in phase 1b 12
WADA statusNot named on the 2026 Prohibited List; class S0 covers drugs under clinical development with no current approval by any governmental health authority 17Not named on the 2026 Prohibited List; S0 applies only to substances with no current approval anywhere, and mazdutide is approved in China 5,17
Who funded the evidenceEli Lilly 1,3,4Innovent Biologics (Chinese trials) and Eli Lilly (US phase 2) 2,18

Retatrutide: what the data says

Retatrutide has completed a phase 3 programme in obesity and type 2 diabetes, all funded by Eli Lilly 3,4,13.

  • In TRIUMPH-1 (2339 adults with obesity without diabetes; human data), mean body-weight change at 80 weeks was -17.6% to -25.0% across three doses vs -3.9% with placebo; knee osteoarthritis pain and apnea-hypopnea index also fell more than with placebo in the relevant subgroups 3.
  • In TRIUMPH-2 (1152 adults with obesity and type 2 diabetes; human data), the change was -11.9% to -18.8% vs -5.1%; treatment discontinuation due to adverse events or death was 8% to 12% in the two higher-dose groups vs 5% with placebo 4.
  • In TRANSCEND-T2D-1 (537 adults; human data), HbA1c fell by 1.69 to 1.94 percentage points vs 0.81 with placebo at 40 weeks 13.

Mazdutide: what the data says

Mazdutide's phase 3 evidence comes from Chinese trials, alongside a US phase 2 trial 2,14,18.

  • In GLORY-1 (610 adults; human data), mean body-weight change at 48 weeks was -11.00% and -14.01% vs +0.30% with placebo 2.
  • In GLORY-2 (461 adults with BMI of 30 or higher; human data), the change at 60 weeks was -16.65% vs -1.50%, and 2.9% stopped treatment because of adverse events vs 0% with placebo 14.
  • In the US phase 2 trial (179 adults; human data), discontinuation due to adverse events reached 20% in the highest-dose group 18.

Key research differences

  • Receptor coverage: retatrutide adds GIP-receptor agonism to the GLP-1 and glucagon activity that it shares with mazdutide 1,2.
  • Regulatory status: mazdutide is approved in China, while retatrutide has no approval identified; neither had a Drugs@FDA record on 24 October 2026 5,6,7.
  • Trial geography: retatrutide's TRIUMPH-2 was run at 92 centres in eight countries, whereas mazdutide's published phase 3 trials were run in China 2,4,14.
  • Outcomes studied: TRIUMPH-1 included knee osteoarthritis pain and sleep apnea endpoints, whereas the mazdutide trials reviewed focus on body weight, HbA1c and cardiometabolic measures 2,3,15.
  • Reported half-life: about 6 days for retatrutide in phase 1b vs a wider 150.9 to 403.5-hour range for mazdutide 10,12.

Where the evidence is limited

No head-to-head trial was identified in the publications or registry searches reviewed 8,9. The trials differ in duration (80 weeks for TRIUMPH-1 vs 48 to 60 weeks for GLORY-1 and GLORY-2), baseline body size, ethnicity and statistical estimands, so their percentages should not be ranked 2,3,14. Both bodies of evidence were funded by the developers, and Eli Lilly is involved in both programmes 3,5.

Frequently asked questions

Does retatrutide lead to more body-weight change than mazdutide?
This cannot be judged from the evidence reviewed. The two have not been compared in the same trial, and their phase 3 trials differ in population, duration and design 2,3,8.
What do retatrutide and mazdutide have in common?
Both activate the glucagon receptor as well as the GLP-1 receptor; retatrutide also activates the GIP receptor 1,2. Mazdutide is co-developed by Eli Lilly with Innovent Biologics, and retatrutide is developed by Eli Lilly 3,5.
Is either approved?
Mazdutide was approved in China in 2025 5. Neither had a Drugs@FDA application record as of 24 October 2026, and retatrutide is described in 2026 publications as under investigation 4,6,7.

References

  1. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial N Engl J Med. 2023
  2. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight (GLORY-1) N Engl J Med. 2025
  3. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1) N Engl J Med. 2026
  4. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial Lancet. 2026
  5. Mazdutide: First Approval Drugs. 2025
  6. Drugs@FDA application data queried through openFDA for retatrutide (no matching application record returned on 24 October 2026) openFDA / Drugs@FDA. 2026
  7. Drugs@FDA application data queried through openFDA for mazdutide (no matching application record returned on 24 October 2026) openFDA / Drugs@FDA. 2026
  8. ClinicalTrials.gov registry search for retatrutide as intervention (33 records, 14 phase 3; retrieved 24 October 2026) ClinicalTrials.gov. 2026
  9. ClinicalTrials.gov registry search for mazdutide as intervention (43 records; phase 3 and phase 4 entries listed; retrieved 24 October 2026) ClinicalTrials.gov. 2026
  10. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial Lancet. 2022
  11. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept Cell Metab. 2022
  12. IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study (full text) EClinicalMedicine. 2021
  13. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial Lancet. 2026
  14. Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial JAMA. 2026
  15. Mazdutide versus placebo in Chinese adults with type 2 diabetes Nature. 2026
  16. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes Nature. 2026
  17. The 2026 Prohibited List - World Anti-Doping Code, as published in the Netherlands Treaty Series (Tractatenblad 2026, 25; Council of Europe Anti-Doping Convention appendix, in force 1 January 2026) Tractatenblad (Official Publications of the Kingdom of the Netherlands). 2026
  18. Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial Lancet Diabetes Endocrinol. 2026

For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page compares published research and is not medical advice or a recommendation.