Mazdutide (IBI362): The Glucagon Twist

A first-in-class GLP-1 / glucagon dual agonist developed by Innovent Biologics (in collaboration with Eli Lilly). Glucagon-receptor activation adds energy expenditure on top of GLP-1 appetite suppression. Phase 3 GLORY-1 data published in NEJM.

🔬 Mazdutide is the China-led answer in the obesity arms race. By targeting both GLP-1 and glucagon, it leans on energy expenditure where Wegovy and Zepbound only suppress intake — that is the bull case for the molecule.

Mean Weight Loss
(GLORY-2, 9mg, 60wk)

GLORY-1 Phase 3
(6mg, 48wk)

GLP-1 + Glucagon
Receptor Activation

Mechanism of Action

How It Works

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GLP-1 Receptor Agonism

Standard GLP-1 effects: insulin release, slowed gastric emptying, central appetite suppression. Drives the intake-reduction half of the weight-loss equation.

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Glucagon Receptor Agonism

Glucagon receptor activation increases hepatic glucose output AND raises basal energy expenditure. The thermogenic component differentiates duals from pure GLP-1s.

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Receptor Balance

Mazdutide is GLP-1-biased (~6:1 GLP-1:glucagon affinity) — enough glucagon to add EE without the hyperglycemic risk of unbiased glucagon agonists. Designed for net weight loss with minimal A1C cost.

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Once-Weekly SubQ

Subcutaneous injection, once weekly. Doses studied: 3, 4.5, 6, 9 mg in obesity trials. 16-week titration to target dose.

Data

What the Data Shows

Mazdutide 9 mg (GLORY-2, 60 wk)

Severe-obesity Chinese adults, BMI ≥30

18.55%

Mazdutide 6 mg (GLORY-1, 48 wk, NEJM)

Phase 3 obesity, Chinese adults

14.84%

Placebo (GLORY-1, 48 wk)

Comparator

0.47%

Patients ≥20% Weight Loss (9 mg, GLORY-2)

Non-diabetic subgroup

~50%

A1C Reduction (DREAMS T2D Trials)

Top-dose effect over 32–48 weeks

~−2%

Bottom Line

Key Takeaways

✅ What We Know

GLP-1 / glucagon dual agonist (GLP-1-biased)
GLORY-1 phase 3 (NEJM): 14.84% mean weight loss at 48 weeks (6 mg)
GLORY-2 phase 3: 18.55% at 60 weeks (9 mg) in severe obesity
DREAMS-1/2/3 trials in T2D show ~2% A1C reduction at top dose
NDA accepted in China for both weight management and glycemic control
Innovent partnered with Eli Lilly on the molecule
Once-weekly subcutaneous injection

⚠️ What We Don't Know

US FDA approval timeline (China-first launch)
Direct head-to-head vs tirzepatide or retatrutide (no published RCT)
Long-term cardiovascular outcomes (CV trial enrolling)
Real-world durability after discontinuation
Whether the GLP-1 / glucagon balance ratio matters vs survodutide / retatrutide

FAQ

Frequently Asked Questions

What is mazdutide?

Mazdutide (IBI362, also known as LY3305677) is a once-weekly subcutaneous GLP-1 / glucagon dual receptor agonist developed by Innovent Biologics in collaboration with Eli Lilly. It combines GLP-1-mediated appetite suppression with glucagon-mediated energy expenditure for the treatment of obesity and type 2 diabetes.

How much weight loss does mazdutide produce?

In phase 3 GLORY-1 (48 weeks, published in NEJM), mazdutide 6 mg produced 14.84% mean body weight loss vs 0.47% placebo. In GLORY-2 (60 weeks, severe obesity), the 9 mg dose achieved 18.55% mean weight loss, with about half of non-diabetic participants losing ≥20% of body weight.

How does mazdutide differ from tirzepatide and survodutide?

Tirzepatide is GLP-1 + GIP. Survodutide and mazdutide are GLP-1 + glucagon (no GIP). The glucagon component adds basal energy expenditure on top of appetite suppression. Retatrutide is a triple agonist (GLP-1 + GIP + glucagon), combining all three.

When will mazdutide be available?

Mazdutide is launched in China (NDA accepted, expected commercial launch 2025–2026 for both obesity and T2D). US approval has no announced timeline as of April 2026; Eli Lilly's focus in the US has been retatrutide and orforglipron.

What are the side effects?

GI predominant (nausea, vomiting, diarrhea, constipation, decreased appetite) consistent with the GLP-1 class. Glucagon-related effects include occasional small heart-rate increases and modest A1C-neutralizing effect that the GLP-1-biased ratio is designed to offset.