Survodutide, mazdutide, tirzepatide and retatrutide are four once-weekly lipidated peptides that each activate more than one receptor, in two different pairings. Tirzepatide and retatrutide are Eli Lilly peptides built on the GIP sequence; survodutide and mazdutide are built on glucagon and pair the glucagon receptor with the GLP-1 receptor. Retatrutide is the only one that hits all three receptors.
The four at a glance
| Tirzepatide | Retatrutide | Survodutide | Mazdutide | |
|---|---|---|---|---|
| Code | LY3298176 |
LY3437943 |
BI 456906 |
LY3305677 / IBI362 |
| Developer | Eli Lilly |
Eli Lilly |
Boehringer Ingelheim, licensed from Zealand Pharma |
Eli Lilly; Innovent Biologics in China |
| Receptors | GIP + GLP-1 |
GIP + GLP-1 + glucagon |
Glucagon + GLP-1 |
Glucagon + GLP-1 |
| Built on | GIP sequence |
GIP sequence |
Modified glucagon sequence |
Oxyntomodulin-like sequence |
| Length | 39 residues |
39 residues |
29 residues |
34 residues |
| Position 2 | Aib |
Aib |
Ac4c (aminocyclobutane carboxylic acid) |
Aib |
| Fatty acid | C20 diacid on Lys20 (γGlu + 2 AEEA) |
C20 diacid on Lys17 (γGlu + AEEA) |
C18 diacid on Lys24 (γGlu + GGSGSG linker) |
C20 diacid on Lys20 (γGlu + 2 AEEA) |
| Molecular weight | 4813.53 Da |
4731.34 g/mol |
4231.63 g/mol |
4563.07 g/mol |
| Reported half-life | About 5 days (FDA label) |
About 6 days (phase 1b) |
No human value published in a primary source |
About 6 to 17 days across participants (phase 1b) |
| Status, October 2026 | FDA-approved (Mounjaro 2022, Zepbound 2023) |
Phase 3; not approved |
Phase 3; not approved |
Approved in China only (2025) |
| In our catalogue | Not stocked |
Sources: FDA labels for Mounjaro and Zepbound; WHO INN lists 126 and 128; the FDA substance registry (GSRS); KEGG DRUG D12225 and D12898; and the papers cited below. Molecular weights are as published for each molecule.
Two families: GIP-based and glucagon-based
The quickest way to sort these four is by the hormone each was built from. Tirzepatide and retatrutide start from GIP (glucose-dependent insulinotropic polypeptide), which is why both act on the GIP receptor. Survodutide and mazdutide start from glucagon (mazdutide is described as an oxyntomodulin analogue, oxyntomodulin being the natural gut hormone that activates both the glucagon and GLP-1 receptors). Both families add GLP-1 receptor activity. Retatrutide sits across the two: it keeps tirzepatide’s GIP and GLP-1 activity and adds glucagon.
All four carry a long fatty diacid that binds albumin, which is what stretches their half-lives from minutes, for the native hormones, to days. GSRS records the same modified lysine, a C20 diacid on γ-glutamate and two AEEA linkers, at position 20 in both tirzepatide and mazdutide, so two Lilly molecules with different receptor partners share the same lipidation.
Survodutide vs mazdutide
These two act on the same receptor pair, glucagon and GLP-1, so the differences are in the molecule and the programme. Survodutide is shorter (29 residues against 34), uses the non-coded amino acid Ac4c at position 2 where mazdutide uses Aib, and carries a C18 rather than a C20 diacid, on a glycine-serine linker at lysine 24. Survodutide’s discovery paper reports its balance between the two receptors, about 1:8 in favour of GLP-1 in human plasma; no peer-reviewed potency ratio has been published for mazdutide. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Zimmermann T, et al. Molecular Metabolism, 2022.
Mazdutide reached approval first: China’s NMPA approved it as Xinermei in June 2025 for chronic weight management and in September 2025 for type 2 diabetes, on the basis of the GLORY and DREAMS phase 3 trials. Survodutide’s phase 3 SYNCHRONIZE trials in obesity reported in 2026, and its MASH programme holds FDA Breakthrough Therapy designation; it had no approval in October 2026. Mazdutide: First Approval. Shirley M. Drugs, 2025; Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. Ji L, et al. NEJM, 2025; Survodutide Once Weekly for the Treatment of Adults with Obesity. le Roux CW, et al. NEJM, 2026.
Mazdutide vs tirzepatide
Both are Lilly peptides with Aib at position 2 and the same C20 diacid on lysine 20, and both activate the GLP-1 receptor. The difference is the second receptor: mazdutide adds the glucagon receptor, tirzepatide the GIP receptor. Tirzepatide is FDA-approved and has the far larger trial record; mazdutide’s trials have so far been run mostly in China, with a US phase 2 trial published in 2026. No trial comparing the two directly was registered on ClinicalTrials.gov in October 2026. Coskun T, et al. Molecular Metabolism, 2018; Hsia SH, et al. Lancet Diabetes & Endocrinology, 2026.
Survodutide vs tirzepatide
They share only the GLP-1 receptor. Survodutide pairs it with the glucagon receptor and is built on glucagon; tirzepatide pairs it with the GIP receptor and is built on GIP. In vitro, Lilly describes tirzepatide as engaging the GIP receptor more than the GLP-1 receptor at clinical exposures, while survodutide’s balance leans toward GLP-1 over glucagon. They come from different companies, and no head-to-head trial was registered in October 2026. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. Willard FS, et al. JCI Insight, 2020.
Where retatrutide fits
Retatrutide adds glucagon-receptor activity to tirzepatide’s GIP and GLP-1 activity, so it overlaps with every other molecule here: with tirzepatide on GIP and GLP-1, and with survodutide and mazdutide on glucagon and GLP-1. Its discovery paper reports balanced glucagon and GLP-1 receptor activity with more GIP receptor activity in vitro. It is in phase 3 (TRIUMPH and TRANSCEND-T2D) and a head-to-head trial against tirzepatide, TRIUMPH-5, was running in October 2026. Coskun T, et al. Cell Metabolism, 2022; Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Li W, et al. Cell Discovery, 2024. More in retatrutide vs tirzepatide.
Where cagrilintide fits
Cagrilintide is often named in the same breath but works through a different system: it is a long-acting analogue of amylin, a pancreatic hormone, and acts on amylin and calcitonin receptors rather than on any incretin receptor. Novo Nordisk tests it combined with semaglutide as CagriSema. See cagrilintide: structure and research.
Head-to-head trials
- Retatrutide vs tirzepatide: TRIUMPH-5 (NCT06662383), running.
- Mazdutide vs semaglutide: DREAMS-3 in type 2 diabetes with obesity (NCT06184568) and GLORY-3 in fatty liver disease (NCT06884293).
- Mazdutide vs dulaglutide: DREAMS-2, published in 2026. Guo L, et al. Nature, 2026.
- Survodutide or mazdutide vs tirzepatide or retatrutide: none registered as of October 2026.
Trial results from different programmes, populations and durations cannot be compared directly, which is why this guide compares the molecules rather than the outcomes.
What we stock
Three of the four are in the catalogue as laboratory reference materials, each size with its own lot certificate: GLP-2 Tirz (tirzepatide), GLP-3 Reta (retatrutide) and survodutide. We do not stock mazdutide. Prices per vial and per milligram are in retatrutide price. None of these materials is for human or veterinary use.
