Guides · PeptideU · 9 min read

Mazdutide Side Effects: What Studies Report

The short answer

Mazdutide is a once-weekly GLP-1 and glucagon receptor dual agonist studied mainly in Chinese adults with obesity, overweight or type 2 diabetes. Across phase 1b, phase 2 and phase 3 trials, researchers reported that gastrointestinal events such as nausea, diarrhoea and vomiting were the most frequently recorded adverse events, generally mild to moderate and most common during dose escalation. Pooled analyses examined tolerability alongside weight outcomes. Long-term and non-Chinese population data remain limited in the published record.

Mazdutide is an investigational and, in some jurisdictions, approved once-weekly peptide that activates both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor. Because it belongs to the incretin class but adds glucagon receptor activity, safety reporting in the published literature has focused on two things: the gastrointestinal events familiar from GLP-1 receptor agonists, and the additional parameters researchers monitored because of the glucagon component. This page summarises what the trials and pooled analyses reported — it does not interpret those findings for any individual and does not describe how the compound is used.

What Mazdutide Is in the Published Literature

Mazdutide (also identified in earlier reports as IBI362) has been evaluated in a sequence of trials conducted largely in Chinese adults. A multiple-ascending-dose phase 1b trial examined 9 mg and 10 mg weekly in Chinese adults with overweight or obesity and described both safety and efficacy outcomes (PMID 36247927). A phase 2 randomised controlled trial then studied the compound in Chinese overweight adults or adults with obesity (PMID 38092790), and a separate phase 2 trial assessed efficacy and safety in Chinese patients with type 2 diabetes (PMID 37943529). A once-weekly phase 3 programme in Chinese adults with obesity or overweight was subsequently published in The New England Journal of Medicine (PMID 40421736).

That progression matters for reading side-effect data: early-phase trials characterise tolerability at ascending exposures in small groups, while later trials report adverse-event rates in larger randomised populations against placebo or an active comparator.

Evidence Tier and How Safety Data Were Collected

Evidence tier: Established — mazdutide has been examined in randomised, double-blind, placebo-controlled human trials, in an active-comparator trial against dulaglutide (PMID 41407860), and in systematic reviews and network meta-analyses that pooled it with other incretin-based agents (PMID 39305981). Safety conclusions on this page therefore rest on controlled human data rather than on preclinical or anecdotal sources.

In these trials, researchers collected treatment-emergent adverse events, recorded severity gradings, tracked discontinuations attributed to adverse events, and monitored laboratory and vital-sign parameters. Those are the categories the published abstracts describe, and they are the categories summarised below.

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Gastrointestinal Adverse Events: What Studies Report

Gastrointestinal complaints dominate the mazdutide safety record. In the phase 3 once-weekly trial in Chinese adults with obesity or overweight, the study reported that the most common adverse events were gastrointestinal — including nausea, diarrhoea and vomiting — and that these were mostly mild to moderate in severity (PMID 40421736). The phase 2 randomised controlled trial in Chinese overweight adults or adults with obesity likewise reported gastrointestinal events as the most frequent adverse events observed during treatment (PMID 38092790).

In the phase 2 type 2 diabetes trial, researchers reported that adverse events were predominantly gastrointestinal and mostly mild or moderate, with the profile consistent with the GLP-1 receptor agonist class (PMID 37943529). A systematic review and meta-analysis of randomised controlled trials pooling diabetic and non-diabetic participants also examined safety alongside weight outcomes and reported gastrointestinal adverse events as the principal tolerability signal (PMID 38440786).

Timing and severity as described

Across these reports, the pattern described is one of events that cluster around the period of dose increase and are graded mild to moderate rather than severe (PMID 40421736). The multiple-ascending-dose phase 1b trial of 9 mg and 10 mg reported that the compound was generally well tolerated at those weekly exposures, with gastrointestinal events again the most common finding (PMID 36247927).

Early-Phase and High-Dose Trials: What Studies Report

Dose-ranging work is where tolerability limits typically appear first. The phase 1b multiple-ascending-dose trial evaluated 9 mg and 10 mg weekly in Chinese adults with overweight or obesity and reported on safety and efficacy at those levels (PMID 36247927). A later high-dose phase 1 trial in adults with overweight or obesity reported body-weight reduction together with its safety observations (PMID 40832785).

These are small, short studies by design. Their value in a safety discussion is descriptive — they indicate which adverse events emerged as exposure rose — and the published abstracts do not support extrapolation to long-term risk. This page therefore does not list exposure levels beyond those stated in the cited titles and abstracts.

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Type 2 Diabetes Trials: What Studies Report

Two 2026 Nature reports extended the diabetes evidence base. One compared mazdutide with placebo in Chinese adults with type 2 diabetes (PMID 41407859), and the other compared it with dulaglutide, an established GLP-1 receptor agonist, in the same population (PMID 41407860). Active-comparator designs are informative for side-effect questions because they show whether an agent's tolerability profile differs from an existing class member rather than only from placebo.

The earlier phase 2 diabetes trial had already reported that the safety profile was consistent with incretin-based therapy, with gastrointestinal events most frequent and mostly mild to moderate (PMID 37943529). Hypoglycaemia is a standard monitored endpoint in diabetes trials, and the published reports describe safety assessment in that context (PMID 41407859).

Comparative and Pooled Analyses: What Studies Report

Network meta-analyses place mazdutide among other weight-management agents. An updated systematic review and network meta-analysis of seven GLP-1 receptor agonists and polyagonists in patients with obesity or overweight included mazdutide among the compared agents and assessed both efficacy and adverse-event outcomes (PMID 39305981). A 2026 BMJ systematic review and network meta-analysis of drugs for adults with overweight or obesity compared agents across efficacy and safety outcomes (PMID 42419792). A systematic review of emerging pharmacotherapies for obesity discussed dual and multi-receptor agonists including their reported tolerability profiles (PMID 39952695), and a meta-analysis of incretin-based dual and triple agonists in overweight or obese individuals pooled safety alongside weight outcomes (PMID 41711462).

Study type	Population described	Safety reporting focus	Source
Phase 1b multiple-ascending-dose	Chinese adults with overweight or obesity	Tolerability at 9 mg and 10 mg weekly	PMID 36247927
High-dose phase 1	Adults with overweight or obesity	Safety alongside body-weight reduction	PMID 40832785
Phase 2 randomised, placebo-controlled	Chinese overweight adults or adults with obesity	Gastrointestinal events most frequent	PMID 38092790
Phase 2 randomised, double-blind, placebo-controlled	Chinese patients with type 2 diabetes	Adverse events mostly mild to moderate	PMID 37943529
Phase 3 once-weekly	Chinese adults with obesity or overweight	Gastrointestinal events most common	PMID 40421736
Active-comparator randomised trial	Chinese adults with type 2 diabetes	Compared against dulaglutide	PMID 41407860
Systematic review and meta-analysis	Diabetic and non-diabetic participants	Pooled efficacy and safety on weight loss	PMID 38440786

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Glucagon-Receptor Considerations: What Studies Report

Mazdutide differs from single-target GLP-1 receptor agonists because it also activates the glucagon receptor, and the published literature describes it explicitly as a GLP-1 and glucagon receptor dual agonist (PMID 36247927). Reviews of emerging obesity pharmacotherapies have discussed dual and triple agonists as a distinct group whose tolerability profiles were assessed separately from single-agonist agents (PMID 39952695), and a pooled analysis of incretin-based dual and triple agonists examined safety outcomes across that class (PMID 41711462).

Readers should note what is not claimed here: this page does not attribute any specific organ-system finding to glucagon receptor activity, because the verified sources cited above do not state such an attribution in the material summarised.

Where the Evidence Is Thin or Absent

Population breadth. The major randomised trials cited here enrolled Chinese adults (PMID 40421736), so adverse-event frequencies in other populations are not established by those reports.
Duration. Published trials describe defined treatment periods; multi-year safety follow-up is not represented in the sources cited on this page.
Rare events. Randomised trials of this size are generally underpowered for uncommon outcomes, and the pooled analyses cited assessed the outcomes their included trials reported (PMID 39305981).
Special groups. Pregnancy, paediatric use, advanced renal or hepatic impairment, and interactions with other medicines are not characterised in the verified sources summarised here; that is an absence of data, not a finding of safety.

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Naming, Trademarks and Regulatory Status

Mazdutide is an international nonproprietary name. Any brand name under which a mazdutide product is marketed in any country is a trademark of its owner, and PeptideU is not affiliated with or endorsed by any manufacturer, sponsor, regulator or trademark holder referenced on this page. Prescription status, approved indications and approved labelling differ by jurisdiction; official prescribing information issued by the relevant regulator, not a summary page, is the authoritative source for label warnings and contraindications.

How This Page Differs From the Course

This page addresses one narrow question — what the published record says about mazdutide's adverse-event profile. The PeptideU mazdutide course covers mechanism, the pharmacology of dual receptor agonism, and how the trial programme was structured. The two are complementary rather than overlapping.

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Educational Disclaimer

This page is for educational purposes only and is not medical advice; consult a licensed physician or qualified healthcare professional about any medicine, symptom or medical decision. Nothing here describes how any compound should be used, and no outcome described in a trial should be read as an expected result for any individual.

References

Frequently asked questions

What adverse events did mazdutide trials most often report?▾

Gastrointestinal events were the most frequently recorded. The phase 3 once-weekly trial in Chinese adults with obesity or overweight reported nausea, diarrhoea and vomiting as the most common adverse events, mostly mild to moderate (PMID 40421736). The phase 2 trial in Chinese overweight adults or adults with obesity reported a similar pattern (PMID 38092790), as did the phase 2 type 2 diabetes trial (PMID 37943529).

Were the reported adverse events severe?▾

Published reports characterised them mainly as mild to moderate rather than severe. Researchers in the phase 3 obesity trial reported that gastrointestinal events were predominantly mild to moderate in severity (PMID 40421736), and the phase 2 diabetes trial described a comparable severity distribution consistent with the incretin class (PMID 37943529). Severity grading in trials does not predict any individual's experience.

Does mazdutide's glucagon receptor activity change its side-effect profile?▾

The literature describes mazdutide as a GLP-1 and glucagon receptor dual agonist (PMID 36247927), and reviews of emerging obesity pharmacotherapies discussed dual and triple agonists as a separate group when summarising tolerability (PMID 39952695). A pooled analysis of incretin-based dual and triple agonists assessed safety across that class (PMID 41711462). Specific organ-system attributions were not stated in these summaries.

What did higher-dose studies report?▾

A multiple-ascending-dose phase 1b trial evaluated 9 mg and 10 mg weekly in Chinese adults with overweight or obesity and reported safety and efficacy at those exposures (PMID 36247927). A separate high-dose phase 1 trial in adults with overweight or obesity reported body-weight reduction together with safety observations (PMID 40832785). Both were small, short studies not designed to characterise long-term risk.

How does mazdutide compare with other weight-management drugs on tolerability?▾

Network meta-analyses have placed it alongside comparators. An updated network meta-analysis of seven GLP-1 receptor agonists and polyagonists included mazdutide and assessed efficacy and adverse-event outcomes (PMID 39305981), and a 2026 BMJ network meta-analysis compared drugs for adults with overweight or obesity across efficacy and safety (PMID 42419792). A randomised trial also compared mazdutide with dulaglutide (PMID 41407860).

Which populations were studied, and what is missing?▾

The major randomised trials cited enrolled Chinese adults with obesity, overweight or type 2 diabetes (PMID 40421736; PMID 41407859). Data on other populations, on multi-year exposure, and on pregnancy, paediatric use or significant organ impairment are not represented in these reports. That is an absence of published data rather than evidence of safety in those groups.

Do these findings apply to any individual?▾

No. Trial adverse-event rates describe groups studied under protocol conditions with monitoring and defined eligibility criteria, and pooled analyses summarise those group-level results (PMID 38440786). They are not predictions for any person. Approved labelling issued by the relevant regulator carries the authoritative warnings and contraindications, and medical questions belong with a licensed physician.

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References

18+ · Educational purposes only
This page summarises published research for education — it is not medical advice, and nothing here is a recommendation to use, purchase, or dose any substance. Study parameters described are what researchers reported, not instructions. Consult a qualified clinician before any health decision.