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Tag: GLP-1 / glucagon dual receptor agonist

Mazdutide

Plain-language summaryIntrigue 72 / 100

Mazdutide is a long-acting dual GLP-1 and glucagon receptor agonist developed by Eli Lilly and out-licensed to Innovent Biologics for development in China. Mechanistically similar to cotadutide and the natural peptide oxyntomodulin, but with a fatty-acid extension supporting once-weekly rather than daily dosing. Phase 2 trials in Chinese type 2 diabetes and obesity populations showed dose-dependent weight loss and HbA1c reduction comparable to or exceeding semaglutide at higher dose tiers. Phase 3 trials are ongoing in China. It is shaping up to be the first dual GLP-1/glucagon agonist to reach a major market, beating its Western competitors. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Our opinion on this compoundEstablished, active research

55/100

Solid dual GLP-1/glucagon agonist with real Phase 2 human signal, but a crowded class and triple-agonist competition cap its ceiling

Look, mazdutide is a genuinely interesting peptide in a genuinely crowded lane. It’s a dual GLP-1/glucagon receptor agonist — modified glucagon backbone, GLP-1 activity grafted in, C18 fatty acid extension for once-weekly dosing — developed by Lilly and out-licensed to Innovent Biologics for the Chinese market. The mechanism does something single GLP-1 agonists don’t: the glucagon arm drives measurable thermogenesis and energy expenditure on top of the GLP-1-mediated appetite suppression, which is at least theoretically a better handle on weight loss than appetite alone.

Here’s the thing though. The dual GLP-1/glucagon mechanism isn’t new. Oxyntomodulin is the natural endogenous template. Cotadutide (AstraZeneca/Pfizer) ran into this space years ago. Survodutide from Boehringer Ingelheim is also in late development on the same dual axis. So mazdutide isn’t defining its category — its competing for second or third position in a class that retatrutide (triple GIP/GLP-1/glucagon) is already threatening to supersede entirely. On differentiation, the compound’s phase 2 data is encouraging — dose-dependent HbA1c reduction and weight outcomes at higher tiers that track with or slightly exceed semaglutide — but thats not the same as being best-in-class when tirzepatide and retatrutide exist.

We think the evidence base is legitimately respectable for where mazdutide sits developmentally. Phase 2 data are real, multi-site, and the DREAMS Phase 3 program in China is ongoing. There’s a clear human signal for the mechanism, which is more than most peptides in the library can claim. What we dont get is the certainty of full Phase 3 readout or the regulatory history that would push evidence quality into the 70s.

From a research bench standpoint, mazdutide is useful primarily as a reference compound for the long-acting dual GLP-1/glucagon format. Investigators studying the glucagon thermogenesis contribution, the energy expenditure differential versus pure GLP-1, or the pharmacokinetic profile of C18-extended dual agonists have a reason to reach for it. It’s not irreplaceable — survodutide and cotadutide cover overlapping ground — but it’s a credible tool in that niche.

Honestly, the compound’s story is hard to tell without returning to the question of where it sits relative to retatrutide. If triple agonists prove out in Phase 3 with the weight loss magnitude early data suggests, dual GLP-1/glucagon becomes a historical stepping stone rather than a destination. Mazdutide is worth watching, worth understanding, and a solid addition to a research library focused on incretin pharmacology. It’s just not the lead compound in that conversation anymore.

Novelty

58

Mechanism promise

73

In-category differentiation

35

Evidence quality

54

Translational signal

62

Research bench value

48

Rationale Mazdutide scores well on mechanism and translational signal — the glucagon-driven energy expenditure layer on top of GLP-1 appetite suppression is real pharmacology with Phase 2 HbA1c and weight data to back it — but differentiation is the key drag: cotadutide, survodutide, and above all retatrutide make mazdutide a follower in a class it doesn’t define. The compound’s China-centric development trajectory also limits global bench relevance.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

GLP-1 / glucagon dual receptor agonist

A long-acting dual GLP-1 and glucagon receptor agonist; under development for obesity and type 2 diabetes.

Abstract

Mazdutide (IBI362, LY3305677; modified peptide with glucagon backbone and GLP-1 modifications; molecular weight approximately 4500 Da) is a dual GLP-1/glucagon receptor agonist developed by Eli Lilly and out-licensed to Innovent Biologics for development in China. The compound is structurally and mechanistically similar to cotadutide and oxyntomodulin, with C18 fatty acid extension for once-weekly dosing. Phase 2 trials in type 2 diabetes and obesity demonstrated dose-dependent HbA1c reduction and weight loss comparable to or exceeding semaglutide at higher dose tiers. Phase 3 trials are ongoing in China (DREAMS program) and US. The dual mechanism produces increased energy expenditure (glucagon effect) on top of the GLP-1 appetite suppression. Used as a reference long-acting dual GLP-1/glucagon agonist.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-296Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026
Cotadutide

Plain-language summaryIntrigue 65 / 100

Cotadutide is a dual GLP-1 and glucagon receptor agonist from AstraZeneca, investigated for type 2 diabetes, fatty liver disease, and obesity. It is a balanced co-agonist (about 5:1 GLP-1 to glucagon). The GLP-1 component does the usual incretin work: insulin release, glucagon suppression, appetite reduction. The glucagon component independently raises energy expenditure and lipolysis, theoretically adding fat-burning on top of appetite suppression. Phase 2 trials showed strong glycemic and weight effects. AstraZeneca de-prioritized it in 2023 in favor of other pipeline assets, leaving its commercial future unclear. The dual-agonist concept lives on in mazdutide and survodutide. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Our opinion on this compoundNovel, promising

63/100

Dual GLP-1/glucagon agonist with a genuine NASH thesis and real Phase 2 metabolic signal

Cotadutide sits in an interesting position in the incretin landscape. It’s not tirzepatide, it’s not retatrutide, and it was never meant to be. What it is: a carefully balanced dual GLP-1/glucagon agonist with a specific research thesis around hepatic fat clearance that pure GLP-1 drugs can’t match on mechanism.

The core design is a roughly 30 amino acid peptide with a C16 fatty acid extension, biased approximately 5:1 GLP-1:glucagon at receptor. The GLP-1 side handles what you’d expect: glucose-dependent insulin secretion, glucagon suppression, appetite attenuation. The glucagon component is where it gets interesting. Glucagon receptor activation in the liver directly drives fatty acid oxidation and lipolysis independent of the GLP-1 effects. Thats the NASH thesis: if you can drive hepatic fat clearance through a mechanism that pure GLP-1 agonism doesnt fully access, you get additive benefit at the liver. Phase 2 data (NCT03205761 and related trials from the AstraZeneca program) showed both superior weight loss versus matched-dose GLP-1 monoagonist controls and meaningful hepatic fat reduction on MRI-PDFF, which is the endpoint NASH investigators actually care about.

We think the mechanism promise here is genuine. The dual-target design isn’t just stacking two agonists; the glucagon axis contributes something mechanistically distinct to the hepatic fat story. That makes cotadutide more than a me-too in the incretin space, even with tirzepatide and retatrutide in the picture. The GIP/GLP-1 axis that tirzepatide exploits and the triple agonism retatrutide is chasing are complementary programs, not direct replacements for this specific hepatic mechanism.

What we don’t love: differentiation is real but incomplete. Retatrutide already includes glucagon co-agonism as part of a more ambitious mechanism stack, which raises the question of where cotadutide fits long-term if triple agonists clear Phase 3. The NASH indication might be the answer. Resmetirom (a THR-beta agonist) is now the first approved MASH therapy, but combination approaches pairing a metabolic backbone compound with a thyroid receptor modulator are an obvious next direction, and cotadutide is a better-characterized reference for the GLP-1/glucagon axis than most alternatives in that conversation.

As a research tool, cotadutide earns its place as the reference dual GLP-1/glucagon agonist for metabolic research programs. If you want to specifically dissect what glucagon co-agonism contributes to a GLP-1 backbone in hepatic and metabolic endpoints, this is the probe you reach for. Evidence base is Phase 2 with Phase 3 ongoing, methodology is solid, and the AstraZeneca program has been transparent with the data. Honest score: real signal, useful probe, genuine mechanism differentiation, but not yet at the top tier of this class until Phase 3 reads out.

Novelty

62

Mechanism promise

76

In-category differentiation

55

Evidence quality

57

Translational signal

63

Research bench value

63

Rationale Scores well on mechanism (dual hepatic-targeted design is mechanistically distinct from pure GLP-1 agonism) and translational signal (Phase 2 data shows HbA1c, weight, and hepatic fat reduction vs matched GLP-1 controls), but differentiation is moderated by retatrutide’s triple agonism and the Phase 3 readout is still pending. Placed novel-promising given the NASH-specific research angle and genuine bench utility as the reference GLP-1/glucagon dual agonist probe.

Editorial commentary from Kodiac biolabs. Not a recommendation, not clinical advice. Research use only.

GLP-1 / glucagon dual receptor agonist

A dual GLP-1 and glucagon receptor agonist; investigated for type 2 diabetes, NASH, and obesity.

Abstract

Cotadutide (MEDI0382; CAS 2125247-22-1; modified peptide with glucagon backbone and GLP-1 modifications; approximately 30 amino acid peptide with C16 fatty acid extension; molecular weight approximately 4140 Da) is a dual GLP-1/glucagon receptor agonist developed at AstraZeneca for type 2 diabetes, non-alcoholic steatohepatitis (NASH), and obesity. The compound is a balanced co-agonist (approximately 5:1 GLP-1:glucagon ratio at receptor). The GLP-1 component drives glucose-dependent insulin secretion, glucagon suppression, and appetite reduction; the glucagon component independently increases hepatic fatty acid oxidation, energy expenditure, and lipolysis. Phase 2 trials demonstrated superior weight loss and HbA1c reduction compared to GLP-1 monoagonists at matched dose, with hepatic fat reduction supporting the NASH indication. Plasma half-life supports once-daily subcutaneous dosing; phase 3 development is ongoing. Used as a reference dual GLP-1/glucagon agonist in metabolic research.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-295Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

May 9, 2026

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