Mazdutide: the GLP-1/glucagon dual agonist explained

Key takeaways

• It is a GLP-1 plus glucagon dual agonist. Mazdutide (also known as IBI362 or LY3305677) is a once-weekly injectable that activates both the GLP-1 receptor and the glucagon receptor, a different second target than tirzepatide .
• GLORY-1 is the headline trial. In this phase 3 study of 610 Chinese adults, mean body weight fell about 11.0 percent at 4 mg and 14.0 percent at 6 mg at week 48, versus a 0.3 percent gain on placebo .
• Roughly half hit the big target. About 49.5 percent of people on 6 mg lost at least 15 percent of their body weight, versus 2.0 percent on placebo .
• The glucagon arm is the differentiator. Adding glucagon-receptor activity is thought to raise energy expenditure and act on liver fat, on top of the appetite suppression GLP-1 provides .
• Approved in China, not the US. Mazdutide was approved for chronic weight management by China's regulator in 2025, but it is not FDA-approved, and every efficacy dataset so far is Chinese-only, which is a real generalizability caveat .

Skip to:

• What mazdutide is, and what the glucagon arm adds
• What the trials actually show
• How it compares to the drugs you know
• Approval status and the caveats that matter
• The bottom line

What mazdutide is, and what the glucagon arm adds

Mazdutide, also called IBI362 or LY3305677, is a once-weekly injectable that activates two receptors at once: the GLP-1 receptor and the glucagon receptor . The GLP-1 half is the part you already know from semaglutide and tirzepatide: it curbs appetite and slows the stomach. The glucagon half is the twist.

Glucagon has a reputation as the hormone that raises blood sugar, which sounds like the wrong direction for a metabolic drug. But at the doses used here, glucagon-receptor activation is thought to increase energy expenditure (the calories you burn at rest) and to act on fat in the liver, while the GLP-1 component keeps appetite and blood sugar in check. The idea is that the two arms together do something neither does alone, which is the same logic behind every multi-agonist in this class .

What the trials actually show

The strongest evidence is GLORY-1, a phase 3 randomized, double-blind, placebo-controlled trial in 610 Chinese adults with obesity or overweight, dosed once weekly for 48 weeks . The weight-loss numbers were dose-dependent and clearly separated from placebo.

The earlier studies pointed the same way. A phase 2 trial in Chinese adults reported about 11.3 percent weight loss at 6 mg by week 24 versus a 1.0 percent gain on placebo , and a phase 1b dose-finding study tested higher doses, with the 9 mg arm reaching about 11.7 percent at week 12 . The consistency across phases is part of why the program advanced.

How it compares to the drugs you know

A 14 percent average at 6 mg lands mazdutide in serious territory, in the same broad neighborhood as the approved GLP-1 weight-loss drugs. But the honest caveat is that there is no published head-to-head trial of mazdutide against semaglutide or tirzepatide, so any ranking is a cross-trial guess, and cross-trial comparisons are unreliable because the populations and trial designs differ .

Where mazdutide is genuinely distinct is mechanism, not just magnitude. Semaglutide hits GLP-1 alone, tirzepatide adds GIP, retatrutide adds both GIP and glucagon for a triple effect, and mazdutide sits in between with GLP-1 plus glucagon . The glucagon arm is what sets it apart from tirzepatide, and it is the reason the drug is also being studied for liver-related endpoints. For the wider comparison of the two approved drugs, see tirzepatide vs semaglutide: what the trials show, and for the triple agonist, see retatrutide's triple-agonist results.

Approval status and the caveats that matter

Mazdutide was approved for chronic weight management by China's drug regulator in 2025, making it the first GLP-1 plus glucagon dual agonist cleared for weight management there, according to its developer's announcement (a company source, so read it as such) . It is not approved by the US FDA, and US development is earlier-stage.

None of this makes mazdutide vaporware: it is a genuinely late-stage, approved-somewhere drug with a distinct mechanism and a real phase 3 trial behind it. It just is not a drug a US reader can get on label today, and the data backing it has a specific population attached.

The bottom line

Mazdutide is a once-weekly GLP-1 plus glucagon dual agonist that delivered about 14 percent weight loss at 6 mg in the phase 3 GLORY-1 trial, with roughly half of those patients losing at least 15 percent . Its glucagon arm, aimed at energy expenditure and liver fat, is what distinguishes it from tirzepatide and is why it carries interest beyond weight alone .

The two things to hold onto: it is approved in China but not the US, and all of its trial evidence is Chinese-only for now . It is a strong addition to the pipeline to track, not a drug to expect at a US pharmacy in the near term.

For research and educational purposes only. Not medical advice.

pepSmart has not commissioned independent clinical review of this article.

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Sources: 4 entries, mostly primary canon (the NEJM phase 3 GLORY-1 trial, a Nature Communications phase 2 trial, and an eClinicalMedicine phase 1b trial), plus one company approval announcement acknowledged inline as the weaker source, last reviewed 2026-06-28.

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