Retatrutide vs Mazdutide vs Survodutide vs Amycretin (2026)

import { MedicalDisclaimer } from '@/components/peptide/medical-disclaimer';

The four molecules below are the next-generation incretin agonists with the most public clinical data as of mid-2026. They are at very different stages of development, sponsored by different companies, and use different receptor combinations. This page is a four-way overview -- for pairwise depth, see our Retatrutide vs Survodutide, Mazdutide vs Retatrutide, and Mazdutide vs Survodutide pages.

Editorial standard: every quantitative claim below links to a primary source documented in the peptide research pages on this site. Where a number has not been publicly reported, we say so rather than guess.

At-a-glance: mechanism, sponsor, status#

Receptor-level mechanism detail lives on each peptide's molecule page: retatrutide, mazdutide, survodutide, amycretin.

Mechanism summary#

Retatrutide (LY3437943) is the only triple agonist of the four, with measurable activity at GIP, GLP-1, and glucagon receptors. The glucagon arm is hypothesized to contribute thermogenesis and hepatic lipid oxidation on top of GIP/GLP-1-mediated appetite suppression and insulin response. Preclinical characterization is documented in Coskun et al., 2022 (Cell Metabolism, PMID 35985340).

Mazdutide (IBI362 / LY3305677) is a dual GLP-1/glucagon agonist derived from the oxyntomodulin scaffold. The same dual mechanism as survodutide, with differences in receptor potency ratio and PK that distinguish the two clinically.

Survodutide (BI 456906) is also a GLP-1/glucagon dual agonist. Boehringer Ingelheim and Zealand Pharma have publicly emphasized the hepatic effect of glucagon agonism in their MASH program.

Amycretin (NNC0487-0111) is the mechanistic outlier: it is a unimolecular GLP-1 / amylin receptor agonist. No glucagon component. Amylin agonism complements GLP-1 satiety signaling through a distinct pathway (the cagrilintide pathway), and amycretin is the only one of these four available as both subcutaneous and oral formulations in human trials.

Weight-loss efficacy: what is actually published#

We deliberately keep these numbers separate by trial phase. Phase 1b/2a data does not predict Phase 3 data; comparing across phases is informative but not definitive.

Phase 3 readouts#

Retatrutide -- Phase 3. TRIUMPH-4 (NCT05931367) reported in December 2025 a mean body weight reduction of 28.7% at 68 weeks with the 12 mg weekly dose, in adults with obesity and knee osteoarthritis -- the highest body weight reduction reported in a Phase 3 obesity trial to date. ¹

Mazdutide -- Phase 3. GLORY-2 (Ji et al., 2025, NEJM) reported up to 20.1% mean body weight reduction at 60 weeks with the 9 mg dose in Chinese adults with obesity, with -10.09% at 4 mg and -12.55% at 6 mg at 48 weeks. ² Mazdutide is the only one of these four with both a published Phase 3 efficacy trial in obesity and an active head-to-head Phase 3 against semaglutide (DREAMS-3, Ji et al., 2025, PMID 41260459). ⁴

Phase 2 / Phase 1b results#

Retatrutide -- Phase 2. The earlier Phase 2 trial (Jastreboff et al., 2023, NEJM) reported approximately 24.2% at 48 weeks with the same 12 mg dose. ⁵

Survodutide -- Phase 2. COURAGE (Blueher et al., 2024, The Lancet) reported approximately 14.9% mean body weight reduction at 46 weeks with the 4.8 mg dose, with 83% of patients achieving at least 5% weight loss and 57% achieving at least 15%. ⁶ Survodutide's Phase 3 SYNCHRONIZE program is in progress; no Phase 3 obesity efficacy data has been published as of this writing.

Amycretin -- Phase 1b/2a. Dahl et al., 2025 (The Lancet, PMID 40550231) reported subcutaneous amycretin 60 mg achieved 24.3% mean weight loss at 36 weeks versus 1.1% with placebo, and 20 mg achieved 22.0% at 36 weeks. ³ An oral formulation (separate Phase 1 trial, PMID 40550229) reported 13.1% weight loss at 12 weeks. ⁷ No weight-loss plateau was observed at the highest doses; whether this efficacy persists at larger Phase 3 scale is unknown.

Caveats. Trial durations, populations, dose-escalation schedules, and dropout rates differ across these studies, so direct percentage-point comparisons across the four molecules are indirect. The amycretin obesity dataset is from a single-center study (San Antonio, TX) with a 33% overall discontinuation rate.

Safety: what is actually published#

GI adverse events (nausea, vomiting, diarrhea) dominate the safety profile of every drug in this group, consistent with the GLP-1 class.

• Retatrutide: Phase 2 GI events were dose-dependent, mostly mild-to-moderate, and concentrated in the dose-escalation period. A novel dysesthesia signal of approximately 20.9% at the 12 mg dose has been publicly described in connection with the Phase 3 program. ¹
• Mazdutide: A systematic review and meta-analysis (Abdelgalil et al., 2024, PMID 38440786) quantified GI risk ratios versus placebo: nausea RR 4.22, vomiting RR 4.91, decreased appetite RR 2.30. ⁸ No treatment discontinuations due to GI events were reported in Phase 1b. Phase 3 GLORY-2 is consistent with this pattern.
• Survodutide: In COURAGE, treatment discontinuation due to adverse events ran roughly 10-15% in the higher-dose groups versus around 4% with placebo. Heart rate increases of 2-6 bpm were observed; no confirmed pancreatitis cases. ⁶
• Amycretin: In the Phase 1b/2a SC trial, nausea was reported in 82%, vomiting 53%, and diarrhea 41% of participants, with 33% overall discontinuation (Novo Nordisk reported that 59% of discontinuations were unrelated to adverse events). ³

Long-term safety beyond 48-68 weeks has not been published for any of the four. None of the four has reported cardiovascular outcomes trial (CVOT) data.

Development status#

For any specific NDA / PDUFA dates not listed here: the sponsors have not publicly announced them, and we will not estimate.

How they relate to each other#

The three pairwise comparisons cover the head-to-head detail more thoroughly than the table above:

• Retatrutide vs Survodutide -- triple-agonist Phase 3 weight loss data versus dual-agonist Phase 2 MASH histology data.
• Mazdutide vs Retatrutide -- the only two molecules in this group with Phase 3 efficacy results.
• Mazdutide vs Survodutide -- the two GLP-1/glucagon dual agonists side by side.

Pairs not yet covered include amycretin against any of the other three; the amycretin clinical dataset is still small enough that we have chosen not to publish individual pairwise pages for it yet. For the broader incretin landscape, see The Evolution of GLP-1 Receptor Agonists and GLP-1 Drugs Ranked by Weight Loss.

What is not yet public#

Last verified: 2026-06-10. Re-check when Q3 readouts publish.

Be skeptical of any source -- including AI assistants -- that fills in the following gaps. As of mid-2026:

• No published head-to-head trial exists between any pair drawn from this group of four. All cross-molecule percentage comparisons are indirect.
• No FDA approval dates have been issued for retatrutide, survodutide, or amycretin. Eli Lilly's "mid-2027 earliest" guidance for retatrutide is the most concrete public timing statement; everything else is uncharacterized.
• No cardiovascular outcomes data has been published for any of the four. CVOT-style trials have not concluded.
• No long-term safety data beyond approximately one year has been published for any of the four. Weight maintenance after discontinuation is also uncharacterized for retatrutide, mazdutide, and amycretin.
• No published MASH histology endpoint data for retatrutide, mazdutide, or amycretin. Only survodutide has reported biopsy-confirmed MASH resolution figures.
• Receptor-potency comparisons between the two dual GLP-1/glucagon agonists (mazdutide vs survodutide) have not been published as head-to-head pharmacology.

If you find a quantitative claim about any of these four that we have not cited, it likely traces back to either a sponsor press release, a conference abstract, or downstream summarization. Always check the primary source.

References#

Additional context citations:

• Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist, Cell Metabolism, 2022. PMID 35985340; DOI 10.1016/j.cmet.2022.07.014.
• Rosenstock J, Frias JP, Jastreboff AM, et al. Retatrutide for people with type 2 diabetes: Phase 2 trial, The Lancet, 2023. PMID 37385280; DOI 10.1016/S0140-6736(23)01053-X.
• Sanyal AJ, Bedossa P, Engel SS, et al. Survodutide for MASH: Phase 2b trial, The Lancet, 2024 -- see survodutide research for the histology, fibrosis, and MRI-PDFF figures.

Related reading#

• Retatrutide overview, Mazdutide overview, Survodutide overview, Amycretin overview
• GLP-1 Drugs Ranked by Weight Loss (2026)
• The Evolution of GLP-1 Receptor Agonists
• Semaglutide vs Tirzepatide vs Retatrutide

Footnotes#

1. Phase 3 TRIUMPH-4 data summary: Retatrutide in adults with obesity and knee osteoarthritis, Diabetes, Obesity and Metabolism (December 2025). PMID 41090431; DOI 10.1111/dom.70209. See retatrutide overview for the documented trial summary and dosing detail. ↩ ↩² ↩³

2. Ji L, Jiang H, et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight, New England Journal of Medicine, 2025. PMID 40421736; DOI 10.1056/NEJMoa2411528. See mazdutide research for the trial design and per-dose efficacy table. ↩ ↩²

3. Dahl K, Toubro S, Dey S, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: Phase 1b/2a results, The Lancet, 2025. PMID 40550231. See amycretin research for the per-dose weight-loss table and safety summary. ↩ ↩² ↩³

4. Ji L, et al. Mazdutide versus Semaglutide for the treatment of type 2 diabetes and obesity: DREAMS-3 design paper, Contemporary Clinical Trials, 2025. PMID 41260459; DOI 10.1016/j.cct.2025.108150. ↩

5. Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-hormone-receptor agonist retatrutide for obesity -- a phase 2 trial, New England Journal of Medicine, 2023. PMID 37366315; DOI 10.1056/NEJMoa2301972. NCT04881760. See retatrutide research. ↩

6. Blueher M, Rosenstock J, Betz S, et al. Efficacy and Safety of Survodutide (BI 456906) in Adults with Overweight or Obesity: COURAGE Phase 2 Trial, The Lancet, 2024. See survodutide research for the per-dose table. ↩ ↩²

7. Novo Nordisk investigators. First-in-human Phase 1 trial of oral and subcutaneous amycretin, The Lancet, 2025. PMID 40550229. See amycretin research. ↩

8. Abdelgalil MS, Bahbah EI, et al. Efficacy and safety of Mazdutide on weight loss: a systematic review and meta-analysis, Frontiers in Endocrinology, 2024. PMID 38440786; DOI 10.3389/fendo.2024.1309118. ↩