Mazdutide vs Retatrutide: Two Receptors or Three

Mazdutide and retatrutide share two receptor targets, GLP-1 and glucagon; retatrutide adds a third, GIP. That one receptor is the whole pharmacological difference between them, and no trial has yet measured what it is worth.

They also sit in very different places. Mazdutide was developed principally in China and is approved there. Retatrutide is Eli Lilly's investigational triple agonist, still working through its phase 3 programme.

What each one is

• Mazdutide (IBI362, LY3305677) is a synthetic analogue built on the oxyntomodulin scaffold, from an Innovent and Lilly lineage. It is a dual agonist at the GLP-1 and glucagon receptors and carries an acyl chain for once-weekly administration. See the mazdutide profile.

• Retatrutide (LY3437943) is a single fatty-acylated peptide from Lilly that activates three receptors — GIP, GLP-1 and glucagon — and is also given once weekly in trials. See the retatrutide profile or the plain-language introduction.

The two approved drugs most people already know make the pattern easier to see. Each step adds one receptor.

Mazdutide is not a step between tirzepatide and retatrutide. It takes a different branch: where tirzepatide adds GIP to GLP-1, mazdutide adds glucagon. Retatrutide combines both additions in one molecule.

Why the glucagon arm matters

The GLP-1 component is common to all four compounds. GLP-1 receptor activation reduces energy intake through central appetite pathways and enhances glucose-dependent insulin secretion.

The glucagon component is what separates mazdutide and retatrutide from the incretin-only drugs. Glucagon receptor activation raises resting energy expenditure and hepatic fat oxidation — a catabolic effect that, in the language of retatrutide's profile, opposes the weight-sparing tendency of incretin action alone. The appeal is that it adds an energy-output lever to a class that otherwise works mainly on intake.

It is not free. Glucagon raises blood glucose, so glucagon agonism carries hyperglycaemic potential. Balancing that against enough incretin activity is the central design problem of the class, and for mazdutide specifically, the ratio between its two receptor activities is what determines its glycaemic profile relative to pure GLP-1 agonists.

Retatrutide's third arm, GIP, is thought to add effects on adipose tissue metabolism and hindbrain signalling — the same component tirzepatide contributes over semaglutide. The retatrutide vs tirzepatide comparison covers that step on its own.

Side by side

What the published trials measured

The two programmes studied different populations, in different countries, against different comparators. Reading them side by side is useful for understanding what each drug has been tested for; it is not a way to rank them.

Mazdutide

• Obesity and overweight. A once-weekly trial in Chinese adults with obesity or overweight, published in the New England Journal of Medicine (Ji 2025).

• Type 2 diabetes against placebo. A trial in Chinese adults with type 2 diabetes (Zhu 2026).

• Type 2 diabetes against dulaglutide. An active-comparator trial, again in Chinese adults (Guo 2026). Dulaglutide is a GLP-1 receptor agonist, so this is the closest thing mazdutide has to a test of whether the glucagon arm adds anything over GLP-1 alone.

• Pooled analyses. Meta-analyses of the randomised trials in non-diabetic adults with overweight or obesity (Azam 2026) and of mazdutide against dulaglutide (Ayesh 2024).

This is the evidence base that supported approval in China. Its limitation for readers elsewhere is generalisability: the trials were conducted in Chinese adults.

Retatrutide

• Obesity, phase 2. 338 adults with obesity, or overweight with a weight-related condition, were randomised to 1, 4, 8 or 12 mg once weekly or placebo for 48 weeks. The primary outcome was percentage change in body weight (Jastreboff 2023).

• Type 2 diabetes, phase 2. 281 adults with type 2 diabetes in a placebo- and active-controlled trial conducted in the USA, testing 0.5, 4, 8 or 12 mg once weekly over 36 weeks, with change in glycated haemoglobin as the outcome (Rosenstock 2023). A body-composition substudy followed (Coskun 2025).

• Liver fat. A phase 2 substudy in adults with obesity and metabolic dysfunction-associated steatotic liver disease measured liver fat content over 48 weeks (Sanyal 2024).

• Phase 3. TRANSCEND-T2D-1, in people with type 2 diabetes inadequately controlled with diet and exercise, has been published (Bajaj 2026). Other phase 3 trials are ongoing.

In the phase 2 trials, doses were reached by stepwise escalation inside the protocol, typically starting at 2 mg and increasing every four weeks. The 1–12 mg span is the range studied, not a schedule, and dose-dependent gastrointestinal effects were reported across it. The retatrutide dosage chart sets out each arm against its source.

We have deliberately not copied efficacy percentages from these papers into a single table. Placed next to each other, figures from trials with different populations, durations and comparators invite exactly the cross-trial ranking the next section warns against.

What the evidence does not show

• Which one causes more weight loss. No trial has randomised participants to mazdutide versus retatrutide. Any "mazdutide vs retatrutide" percentage you see is arithmetic across separate trials.

• What GIP adds on top of GLP-1 and glucagon. Retatrutide differs from mazdutide by one receptor, but no study isolates that receptor's contribution in this combination.

• Transfer between populations. Mazdutide's published trials were in Chinese adults; retatrutide's type 2 diabetes phase 2 trial was conducted in the USA. Baseline weight, diet and background therapy all differ between such populations.

• Long-term safety. Mazdutide's approval rests on a programme conducted in one country. Retatrutide's full phase 3 safety picture has not yet been published.

Indirect methods do exist. A Bayesian network meta-analysis has compared GLP-1 receptor agonists, dual agonists and retatrutide for weight loss (Sinha 2025). Network meta-analyses are useful for generating hypotheses, but they rest on the assumption that the underlying trials are comparable, which is exactly the assumption in doubt here.

The only direct comparison involving either drug in our data is NCT06260722, a phase 3 trial of retatrutide against semaglutide in 1,250 adults with obesity. It is listed as active, not recruiting, with no results posted — and it does not include mazdutide. The retatrutide vs semaglutide comparison covers it.

Reported side effects

Both profiles are dominated by gastrointestinal effects, as expected for the class. Retatrutide's reported effects include nausea, diarrhoea, constipation and increased heart rate. For mazdutide, our profile records gastrointestinal adverse events and a possible increase in heart rate. The retatrutide side effects guide goes into the trial reporting in more depth.

The vial math

For anyone working through concentration arithmetic for research purposes, the calculation depends only on vial mass and water volume, not on which molecule is in the vial.

Those are the retatrutide reconstitution examples from our profile. The retatrutide calculator works through them, and the general peptide calculator handles any other vial, including mazdutide, for which we hold no reconstitution data. The insulin syringe units converter explains the unit markings.

Frequently asked questions

Is mazdutide the same as retatrutide?

No. Both are single molecules that activate the GLP-1 and glucagon receptors, but retatrutide also activates the GIP receptor. Mazdutide is a dual agonist; retatrutide is a triple agonist.

Is mazdutide stronger than retatrutide?

There is no way to say from the published evidence. No trial has compared them directly, and their trials differ in population, country, duration and comparator.

Is mazdutide approved anywhere?

Yes, in China. The National Medical Products Administration approved it in 2025 for weight management and type 2 diabetes, marketed as Xinermei. It is not FDA-approved.

Is retatrutide FDA-approved?

No. Retatrutide is an investigational drug. Its phase 2 trials are published, one phase 3 trial has been published, and further phase 3 trials are ongoing.

Are mazdutide and retatrutide banned in sport?

Retatrutide is prohibited by WADA under the S0 category for non-approved substances. Mazdutide is not listed by name in our data, which is not the same as being permitted; athletes subject to testing should check with their anti-doping authority.