Evidence memo / Metabolic & weight

Mazdutide

Also: IBI362 · LY3305677 · GLP-1/glucagon dual agonist · oxyntomodulin analog

Mazdutide is a weekly injectable that activates two gut-hormone receptors at once, GLP-1 and glucagon, modeled on the natural hormone oxyntomodulin. It produces substantial weight loss and was approved in China in 2025 for weight management, while remaining investigational (not FDA-approved) elsewhere. The Watchlist boundary is reading it as a promising, regionally-approved dual agonist whose broader regulatory and long-term evidence is still maturing.

Controlled human dataPhase 2 / Phase 3Investigational

The verdict

Our read at a glance.

Whether mazdutide's dual GLP-1/glucagon agonism delivers durable weight and metabolic benefits with acceptable safety, and how to weigh its China approval against its still-developing global evidence and regulatory status.

The signal
Phase 2 and phase 3 trials, largely in China, show mazdutide produces significant weight loss versus placebo and improves blood sugar, which led to its 2025 approval in China for weight management. Liver-fat and metabolic effects are being studied.
The unknown
Its long-term safety and durability, head-to-head standing against tirzepatide and other incretins, whether the glucagon component's energy-expenditure and liver benefits hold up, and whether it gains approval beyond China.
Our read
A promising next-generation obesity drug: a GLP-1/glucagon dual agonist that clearly drives weight loss and won approval in China in 2025, but whose long-term safety, durability, and standing against the leading incretins are still being worked out, and which is not yet approved outside China. Read it as regionally approved and rapidly maturing, not a finished, globally-established therapy.

The mechanism

How it works.

Gut hormones released after eating tell the body to feel full and to handle sugar and fat; the natural hormone oxyntomodulin happens to switch on two of these receptors at once, GLP-1 and glucagon. Mazdutide is a lab-made, long-acting copy of that dual-action design. Through the GLP-1 receptor it curbs appetite, slows stomach emptying, and improves insulin release (the same way drugs like semaglutide work); through the glucagon receptor it is thought to raise energy expenditure and help clear fat from the liver. Combining both is meant to add to the weight and metabolic benefits of GLP-1 alone, and a fatty-acid tail lets it last about a week per injection.

Safety & regulatory boundary

The consequential part.

Like other incretin drugs, mazdutide commonly causes nausea, vomiting, and diarrhea, especially early; the added glucagon activity raises questions about heart rate and blood-sugar effects that ongoing trials are tracking. It is approved in China for weight management but is investigational and not FDA-approved in the US or most other regions, so it should not be treated as broadly available or fully established. It is a prescription drug, not a supplement or research-chemical product.

What's next

What we're watching.

Global regulatory decisions, long-term outcome and safety data, liver (MASH) results, and head-to-head comparisons with tirzepatide and other dual and triple agonists.

Context

Why this is discussed.

Mazdutide is part of the next wave of obesity drugs that hit more than one target. By switching on the glucagon receptor in addition to GLP-1, it aims to add energy-burning and liver-fat benefits on top of the appetite suppression that GLP-1 drugs already provide. It is one of the dual agonists (alongside survodutide) following tirzepatide and retatrutide.

The evidence base

10 cited references.

Keep reading

Related published memos.