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Mazdutide Side Effects: What the Trials Actually Measured

Written by Peptide Insider Research Team

The Peptide Insider research team verifies every claim against PubMed and ClinicalTrials.gov, reads vendor certificates of analysis lot by lot, and tracks pricing across U.S. research-peptide vendors. Every article links its sources.

REVIEWED BY

Marcus Reinhardt — Chemical Researcher, Lead Analyst & Peptide Research Advisor

Marcus Reinhardt is a chemical researcher specializing in sustainable materials and advanced formulation science, with research experience in compound development and health optimization. He reviews all Peptide Insider educational content for scientific accuracy, strength of supporting evidence, and practical relevance. Editorial team.

Mazdutide side effects — what the trials actually measured

Written by Marcus Reinhardt · Lead Analyst, Peptide Insider · LinkedIn

Evidence-first peptide coverage — every claim on this page is linked to its primary source and reviewed against our editorial policy

Citations verified against PubMed · Published: 2026-09-04 · Last updated: 2026-09-07

Mazdutide side effects are documented across a larger phase 3 program than any research-market compound except retatrutide: a 610-person, 48-week obesity trial in the New England Journal of Medicine, a 461-person, 60-week trial of the 9 mg dose in JAMA, two phase 3 diabetes trials in Nature (320 and 731 participants), and a Lilly-run phase 1 that pushed the dose to 16 mg. The short answer: the side effects are gastrointestinal, mostly mild to moderate, and at 9 mg frequent enough that vomiting — not nausea — topped the table, at 53.1% versus 1.3% on placebo. This page gives you the actual rates, with citations, notes that nearly all come from Chinese populations, and flags where the trial data stops applying to a research vial.

Quick Answer: The Most Common Mazdutide Side Effects

In the 60-week GLORY-2 trial of 9 mg mazdutide, the most common adverse events were vomiting (53.1% vs 1.3% on placebo), nausea (46.9% vs 3.2%), and diarrhea (39.4% vs 6.5%); most were mild to moderate, and 2.9% stopped treatment for adverse events versus 0% on placebo. At 4 mg and 6 mg in the 48-week GLORY-1 trial, discontinuation for adverse events was 1.5% and 0.5% against 1.0% on placebo. In the type 2 diabetes phase 2: diarrhea (36%), decreased appetite (29%), nausea (23%), vomiting (14%), hypoglycemia (10%, vs 8% on placebo). Self-reported experiences from Reddit are summarized further down; they are anecdotes, not data.

★The Documented Experience of 2,600+ Trial Participants

The most complete “user experience” of mazdutide belongs to the people who took it under observation — 610 in GLORY-1, 461 in GLORY-2, 320 and 731 in the Nature diabetes trials, 248 in the obesity phase 2. The typical arc: weight fell steadily through 48 and 60 weeks (the 9 mg group averaged a 16.65% reduction), and the GI effects — diarrhea and nausea at lower doses, vomiting first at 9 mg — arrived with the dose, mostly mild to moderate.

How tolerable did participants find it? adverse events led to discontinuation in 1.5% of the 4 mg group and 0.5% of the 6 mg group in GLORY-1 — against 1.0% on placebo — and in 2.9% of the 9 mg group in GLORY-2. The Nature investigators called the diabetes profile “favourable”; the JAMA investigators, at 9 mg, wrote that participants “experienced gastrointestinal adverse reactions.” Both are true; the dose is the difference.

What that experience came with: screening, monitoring, pharmaceutical-grade product, and clinician-managed dosing — none of which ships with a research vial.

Compiled from the published trials (PMID 40421736, PMID 42251595, PMID 41407859) — not from testimonials. When we publish an individual account here, it will be a real person, named with permission.

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In This Guide

What Is Mazdutide?

Mazdutide is a once-weekly dual agonist of the glucagon-like peptide-1 (GLP-1) and glucagon receptors, developed in China by Innovent Biologics, with Eli Lilly running the high-dose phase 1 (PMID 40832785). It sits one receptor short of retatrutide — GLP-1 plus glucagon, without GIP. Its trial program is unusually mature: two phase 3 obesity trials, GLORY-1 at 4 mg and 6 mg (PMID 40421736) and GLORY-2 at 9 mg (PMID 42251595), plus two phase 3 diabetes trials in Nature. The headline: a 16.65% average weight reduction at 60 weeks on 9 mg, versus 1.50% on placebo (PMID 42251595). In the United States it has no FDA approval; every vial sold under this name here is research-market material.

How It Works — and Why the Glucagon Half Changes the Side-Effect Math

GLP-1 agonism slows gastric emptying and suppresses appetite — the source of the GI effects that define the class, covered in our GLP-1 peptide guide. Glucagon agonism adds energy expenditure and liver-fat mobilization. The Nature investigators judged the most common events “consistent with GLP-1R agonists” (PMID 41407859). But the dulaglutide comparison is the tell: at 4 mg and 6 mg, “the incidence of gastrointestinal adverse events was higher for mazdutide than for dulaglutide” (PMID 41407860). The glucagon half buys efficacy and costs GI tolerability at the same time.

KEY TAKEAWAY

Mazdutide’s side effects are the GLP-1 class profile running hotter than an approved GLP-1: against 1.5 mg dulaglutide it produced more weight loss and more GI events in the same trial. At 9 mg, vomiting outranked nausea. What the dose adds in effect it adds in side effect.

The Trial Numbers That Matter

Seven datasets do the work here. Obesity: GLORY-1 (NEJM, 2025) — 610 Chinese adults randomized to 4 mg, 6 mg, or placebo for 48 weeks (PMID 40421736); GLORY-2 (JAMA, 2026) — 461 treated adults randomized 2:1 to 9 mg or placebo for 60 weeks (PMID 42251595); the obesity phase 2 (Nature Communications, 2023) — 248 adults on 3 mg, 4.5 mg, 6 mg, or placebo for 24 weeks (PMID 38092790); and Lilly’s high-dose phase 1 — 32 adults, 24 escalated toward 16 mg and 8 on placebo, for 20 weeks (PMID 40832785). Type 2 diabetes: the placebo-controlled phase 3 (Nature, 2026) — 320 adults on 4 mg, 6 mg, or placebo for 24 weeks (PMID 41407859); DREAMS-2 (Nature, 2026) — 731 adults on 4 mg, 6 mg, or 1.5 mg dulaglutide for 28 weeks (PMID 41407860); and the diabetes phase 2 (Diabetes Care, 2024) — 3 mg, 4.5 mg, 6 mg, dulaglutide, or placebo for 20 weeks (PMID 37943529).

Gastrointestinal Side Effects: The Real Rates

Two abstracts give per-event numbers. GLORY-2, 9 mg for 60 weeks: vomiting in 53.1% of mazdutide participants versus 1.3% on placebo, nausea in 46.9% versus 3.2%, diarrhea in 39.4% versus 6.5% — most mild to moderate (PMID 42251595). The diabetes phase 2, up to 6 mg for 20 weeks: diarrhea 36%, decreased appetite 29%, nausea 23%, vomiting 14% (PMID 37943529) — that abstract gives a placebo rate only for hypoglycemia, so there is no GI placebo column to report. The GLORY-2 placebo floors are strikingly low — 1.3% vomiting, 3.2% nausea — so almost the entire GI burden at 9 mg is attributable to the drug.

The other four abstracts name the leading events — GI events “mostly mild to moderate” in GLORY-1 (PMID 40421736); diarrhea, nausea, and upper respiratory tract infection in the obesity phase 2 (PMID 38092790); diarrhea, decreased appetite, and nausea in the placebo-controlled diabetes phase 3 (PMID 41407859); diarrhea, nausea, and vomiting in DREAMS-2, at higher incidence than on dulaglutide (PMID 41407860) — without percentages, so neither do we.

PERSONAL OBSERVATION — PI EDITORIAL

Reading GLORY-1 and GLORY-2 side by side, what struck us was the gap between two abstracts from the same sponsor, a year apart. The NEJM paper at 4 and 6 mg says “gastrointestinal and mostly mild to moderate” and stops. The JAMA paper at 9 mg gives you 53.1% vomiting and 46.9% nausea against near-zero placebo. One reads like a tolerability story, the other like a warning label; the dose went from 6 to 9.

Bar chart from the mazdutide GLORY-2 trial, 9 mg versus placebo over 60 weeks: vomiting 53.1% vs 1.3%, nausea 46.9% vs 3.2%, diarrhea 39.4% vs 6.5%.
Chart: the three most common adverse events in GLORY-2, mazdutide 9 mg (n=307) versus placebo (n=154), plotted from the published rates (PMID 42251595). Most events were mild to moderate; the near-zero placebo floor for vomiting is what makes that column the one to watch.

Vomiting: The Side Effect That Led the 9 mg Table

In most GLP-1-family trials nausea leads and vomiting sits well behind it. GLORY-2 inverted that: vomiting 53.1% versus 1.3% on placebo, ahead of nausea at 46.9% versus 3.2% (PMID 42251595). More than half the 9 mg group vomited at some point in 60 weeks — the most important number on this page. Two caveats the abstract supports: “most of the adverse events were mild to moderate,” and only 2.9% discontinued for adverse events versus 0% on placebo, so for most participants vomiting was tolerated rather than treatment-ending. The abstract does not report episode counts, timing, or anti-emetic use. At lower doses it was a minor entry — 14% in the diabetes phase 2 (PMID 37943529).

Injection-Site Reactions

None of the seven abstracts reports an injection-site reaction rate or names administration-site events among the most common adverse events (PMID 40421736, PMID 42251595, PMID 37943529) — which tells you they were not a leading category, and nothing more precise. Mazdutide is a once-weekly subcutaneous injection like the rest of its family, so the standard handling picture applies.

PRACTICAL NOTES — STANDARD SUBCUTANEOUS HANDLING

  • Reconstituted solutions brought to room temperature before use are standard practice in clinical settings
  • Site rotation (abdomen, thigh, upper arm) is how trial protocols manage repeated weekly injections
  • Sterile technique — clean site, single-use needles — is non-negotiable in any protocol, trial or lab
  • Our bacteriostatic water guide covers reconstitution handling in detail

Beyond the Gut: What Else the Trials Recorded

Outside the gut, the abstracts give three hard facts and one silence. Hypoglycemia: 10% of mazdutide participants versus 8% on placebo in the diabetes phase 2 (PMID 37943529) — a small excess, and the only non-GI event with a placebo column in any mazdutide abstract. Decreased appetite: 29% in the same trial and among the most common events in the placebo-controlled diabetes phase 3 (PMID 41407859) — the mechanism doing its job. Serious adverse events: none in the 32-person phase 1 (PMID 40832785); no other abstract gives a count or mentions a death either way. The silence: no mazdutide abstract mentions heart rate. Since glucagon agonism drives the heart-rate increase reported for retatrutide, that absence is a gap in the abstracts, not evidence of a difference.

What Users Report: Self-Reported Effects From Reddit

The trial tables above cover pharmaceutical mazdutide taken alone at 4, 6 and 9 mg; they are silent on heart rate and on the tirzepatide stacks Reddit actually uses. We searched Reddit on September 5, 2026, found 72 relevant posts from 2024 to 2026, and read the comment threads of ten, across r/Mazdutide, r/Peptides, r/PeptideForum and r/BiohackingU. Everything below is paraphrased and linked, uses no usernames, and describes products nobody verified. Two caveats: the mid-2024 posters are mostly self-described participants in a US Lilly trial who could not know whether they got drug or placebo, and nearly every later poster added mazdutide to tirzepatide as a homemade retatrutide, so nothing there isolates mazdutide.

The most distinctive reports are cardiac, and they fill a gap the trials left open. An early r/Mazdutide thread asked whether others felt they had “quickly polished off two pots of coffee” (r/Mazdutide). A GLP-1 veteran who took 3 mg as a first dose replied with palpitations twelve hours later, a resting heart rate around 130 and days too sick to eat. An older solo user switching from retatrutide found caffeine intolerable and resting heart rate up the day after a first 1.5 mg shot (thread). Against these, a poster with atrial fibrillation who had quit retatrutide over heart rate added up to 3 mg to 15 mg of tirzepatide and found resting heart rate no worse than on tirzepatide alone (r/Mazdutide); another on the same stack measured it well below retatrutide (r/Peptides).

Gastrointestinal effects appear, track dose, and stop short of the vomiting the trials recorded. A stacker who could not tolerate tirzepatide above 5 mg found 2 and 4 mg of mazdutide alongside it uneventful, hit heavy diarrhea at 6 mg over 7.5 mg of tirzepatide, and dropped back (thread). A trial participant with PCOS described morning-sickness-like nausea after her second shot, then bloating, early waking, nausea swinging mild to severe after titrating up, ondansetron and constipation, but no fatigue (r/Mazdutide). Nobody in the ten threads described vomiting, the event that led the 9 mg table above.

In the trial threads, exhaustion and vanished appetite dominated, and nobody knew their arm. A second woman with PCOS on an escalating arm had a headache and leg cramps in week one, then close to a month too exhausted to stay awake and near fainting, with no appetite; she finished the study 80 pounds lighter and later regained 30 (thread). Another participant slept more than eight hours after the first clinic dose and, at 3 mg, had to make a conscious effort to eat. One relayed a coordinator’s story of a fixed-high-dose participant calling 911 overnight: hearsay, without detail, and the only emergency in the record.

Gray-market stackers split between broken plateaus and nothing at all, with one report of emotional numbness. The most-upvoted reply in the stacking thread reported zero side effects on tirzepatide plus mazdutide; another poster broke a long stall with the same stack and felt an energy lift within a day (r/Mazdutide). A slow responder got appetite suppression back after swapping retatrutide for 5 mg of mazdutide beside tirzepatide (r/Mazdutide). One poster said mazdutide did nothing, one on 10 mg stalled after 20 pounds (thread), and one found it only restored the energy tirzepatide took (r/PeptideForum). A user who spent a month on mazdutide alone called it the only GLP-1 that left them emotionless and numb, and said it worsened their ADHD (r/BiohackingU).

The liver-enzyme thread in every mazdutide search is not about mazdutide. Its author was on tirzepatide, retatrutide and atorvastatin when ALT hit ten times normal and a hepatologist called it probable drug-induced liver injury; the author stopped retatrutide and the statin and ordered mazdutide to try next, but had not taken any when posting (r/Mazdutide). No one on mazdutide reported liver-enzyme changes.

HOW TO READ SELF-REPORTS

Tables and anecdotes agree the gut is where mazdutide bites and dose sets the bite; they part on which symptom, since nobody here reports the vomiting that led the 9 mg table. The anecdotes add a heart-rate signal the abstracts never measured, from three people, one of whom chose a higher first dose and one fresh off retatrutide. No frequency follows: trial posters might have been on placebo, stackers were also on tirzepatide, and the whole record is about twenty people.

When Side Effects Happen — and When They Fade

No published mazdutide data supports a week-by-week side-effect calendar; what the abstracts say about timing is indirect. The phase 1 used two dose-escalation regimens to reach 16 mg (PMID 40832785) — escalation being the class’s standard answer to GI events at dose starts. The placebo-controlled diabetes phase 3 ran 24 weeks of randomized treatment plus a 24-week extension (PMID 41407859); the abstract reports only week 24. Discontinuation for adverse events was low everywhere — 0.5% to 1.5% in GLORY-1, 2.9% in GLORY-2 — consistent with events that settle rather than accumulate, and “consistent with” is as far as the abstracts go.

Long-Term Safety: What 60 Weeks Can and Can’t Tell You

The longest published exposure is GLORY-2’s 60 weeks in 461 treated participants (PMID 42251595), then GLORY-1’s 48 weeks in 610 (PMID 40421736) — more than a year of monitored data at the top dose. Geography: every phase 2 and phase 3 participant was enrolled in China; Lilly’s 32-person phase 1 abstract does not say where it enrolled. Time: 60 weeks is the horizon; nobody has multi-year data. The JAMA investigators’ conclusion is the fairest summary — clinically meaningful weight reduction, “but participants receiving the drug experienced gastrointestinal adverse reactions” (PMID 42251595).

Who the Trials Enrolled — and Who They Didn’t

GLORY-1 enrolled adults aged 18 to 75 with a BMI of at least 28, or 24 to less than 28 with a weight-related condition, with a mean baseline BMI of 31.1 (PMID 40421736). GLORY-2 enrolled a young cohort: mean age 33.9, mean BMI 34.3, 64.0% female, 16.1% with type 2 diabetes (PMID 42251595). The diabetes trials admitted adults on diet and exercise or stable metformin, with a mean diabetes duration of just 1.9 years in the placebo-controlled phase 3 (PMID 41407859). Left out: anyone on insulin, anyone with long-standing diabetes, anyone outside China — and a cohort averaging 33.9 years says little about older adults. Every rate here came from screened, monitored people with clinicians watching.

Managing and Minimizing Side Effects: What the Trials Did

The trials’ side-effect management was structural. GLORY-2 delivered mazdutide “as an adjunct to a reduced calorie diet and increased physical activity” (PMID 42251595); the phase 1 used two escalation regimens to reach 16 mg (PMID 40832785). No anti-nausea co-medication appears in any abstract. The one measurable lever is dose: discontinuation for adverse events in GLORY-1 was 1.5% at 4 mg and 0.5% at 6 mg — in the same range as placebo’s 1.0% — while at 9 mg in GLORY-2 it was 2.9% against 0% (PMID 42251595). We report the dose arms as trial architecture, not a protocol recommendation.

Dose and Side Effects: The Correlation Is Measured

The dose–effect relationship was mapped across the full dose range. Weight loss at 24 weeks in the obesity phase 2: 6.7% (3 mg), 10.4% (4.5 mg), 11.3% (6 mg) versus a 1.0% gain on placebo (PMID 38092790). At 48 weeks in GLORY-1: 11.00% (4 mg) and 14.01% (6 mg) versus a 0.30% gain (PMID 40421736). At 60 weeks on 9 mg: 16.65% versus 1.50% (PMID 42251595). At 20 weeks escalating to 16 mg: 20.0% and 21.0% in the two cohorts versus 0.1% (PMID 40832785). The side effects climbed with it — from “well tolerated” at up to 6 mg to vomiting in 53.1% at 9 mg. No published dose separates effect from side effect.

DID YOU KNOW

Eli Lilly’s phase 1 took mazdutide to 16 mg — “higher than previously studied” — and 66.7% and 75.0% of the two cohorts lost 15% or more of their body weight in 20 weeks, with no serious adverse events (PMID 40832785). Twenty-four people. GLORY-2, with 307 on 9 mg, is where the incidence numbers live.

Mazdutide Alone vs Stacked: What the Data Covers

Every published mazdutide safety number comes from mazdutide alone or mazdutide against dulaglutide. No combination trial has been published. The stacks discussed on research forums — mazdutide plus an amylin analogue such as cagrilintide, or alongside retatrutide — have no human safety data at all, and the 9 mg monotherapy numbers above are not a floor anyone should build on. Our GLP-3 sourcing guide covers the market side of this family separately.

How Mazdutide Compares to Retatrutide, Survodutide, and the GLP-1s

No trial pits mazdutide against retatrutide or survodutide, so those comparisons are cross-trial — different populations, durations, and reporting — a real limitation. Mazdutide does have one in-trial comparator: 1.5 mg dulaglutide, twice. In DREAMS-2 it beat dulaglutide on HbA1c (treatment differences of -0.24% and -0.30% at 4 mg and 6 mg) and weight (-3.78% and -5.76%) while producing more GI events (PMID 41407860); in the diabetes phase 2 it reached 7.1% weight loss against dulaglutide’s 2.7% (PMID 37943529). That is the dual-agonist bargain in one trial: more effect, more GI. For the triple agonist that adds GIP, see retatrutide side effects; for the other GLP-1/glucagon dual, survodutide side effects; for the antibody-conjugated route, MariTide side effects. Our retatrutide primer covers the receptor pharmacology behind all of them.

Where the Trial Data Stops: The Research-Vial Reality

Everything above describes pharmaceutical-grade mazdutide dosed under supervision. A lyophilized vial from a research-chemical storefront shares a molecule name with that product and nothing else verifiable. The gap shows up three ways: identity and purity (a batch-matched COA is the only evidence the vial contains dose-accurate mazdutide — our lab-testing guide explains what a real one shows), concentration arithmetic (reconstitution with bacteriostatic water is on the buyer — our peptide calculator handles the math), and no medical monitoring, the invisible ingredient in every trial safety table. Compounds in this channel are sold strictly for non-human research use.

Sourcing and Verification

Mazdutide listings are newer and thinner than retatrutide’s. The checklist is unchanged: a batch-matched COA naming compound and quantity, independent third-party testing with a verifiable report number, and hard skepticism toward any listing quoting GLORY-2’s 16.65% as if it applied to the vial. (Disclosure: some links on this site are affiliate links; they do not change what we report.) Our vendor reviews show what passing paperwork looks like, and our guide library covers verification. We do not yet track live mazdutide prices; when our tested vendors stock it, this section gets the table.

US Regulatory Status

In the United States, mazdutide is an investigational compound with no FDA approval. Its development and every phase 3 trial belong to Innovent Biologics in China (PMID 40421736). Whatever its status with China’s regulator, no US prescription version exists, every vial in US circulation is research-market material sold for non-human research use, and no regulator has evaluated any of those products for identity, purity, or the safety profile above. Our coverage of the FDA’s July 2026 peptide vote tracks the wider regulatory climate. When US status changes, this section changes with it.

PERSONAL OBSERVATION — PI EDITORIAL

In listings we’ve reviewed, mazdutide is sold as retatrutide’s smaller sibling, and the GLORY-2 vomiting figure appears on none of them. The trial compound was made under pharmaceutical manufacturing controls; the vial was made by whoever filled the order. The sequence is familiar: the efficacy number travels, the tolerability number does not, and the COA is the only sentence of this page that applies to the vial in your hand.

Frequently Asked Questions

What are the most common mazdutide side effects?

Gastrointestinal. In the 60-week GLORY-2 trial at 9 mg: vomiting 53.1% vs 1.3% on placebo, nausea 46.9% vs 3.2%, diarrhea 39.4% vs 6.5%, mostly mild to moderate. In the type 2 diabetes phase 2 at up to 6 mg: diarrhea 36%, decreased appetite 29%, nausea 23%, vomiting 14%.

Does mazdutide cause vomiting?

At 9 mg it was the most common adverse event — 53.1% of participants versus 1.3% on placebo over 60 weeks. Most events were mild to moderate and only 2.9% of the mazdutide group stopped treatment for adverse events.

How much weight did people lose on mazdutide in trials?

11.00% (4 mg) and 14.01% (6 mg) at 48 weeks versus a 0.30% gain on placebo in GLORY-1; 16.65% at 60 weeks on 9 mg versus 1.50% in GLORY-2; and 20.0% to 21.0% at 20 weeks in the 16 mg phase 1 cohorts versus 0.1%.

Is mazdutide safe?

In trials, adverse events were mostly mild-to-moderate GI events; discontinuation for adverse events was 0.5% to 1.5% at 4 and 6 mg (vs 1.0% placebo) and 2.9% at 9 mg (vs 0%), and the phase 1 reported no serious adverse events. All measured in screened, monitored Chinese trial populations on pharmaceutical-grade product — not research-market vials.

How do mazdutide side effects compare to retatrutide?

No head-to-head trial exists, and the populations differ. Both are GI-led glucagon-containing agonists; mazdutide lacks retatrutide’s GIP component. Mazdutide’s only in-trial comparator is dulaglutide, against which it produced more weight loss and more GI events.

Does mazdutide cause hypoglycemia?

In the type 2 diabetes phase 2, hypoglycemia occurred in 10% of mazdutide participants versus 8% on placebo — a small excess. The obesity trial abstracts do not report it, and no abstract reports severe hypoglycemia either way.

Glossary of Terms

  • Dual agonist: a single molecule that activates two receptors — for mazdutide, GLP-1 and glucagon.
  • Glucagon receptor agonism: the component that raises energy expenditure and mobilizes liver fat — and the half of mazdutide that a plain GLP-1 lacks.
  • GLORY-1 / GLORY-2: Innovent’s phase 3 obesity trials — 4 mg and 6 mg for 48 weeks, and 9 mg for 60 weeks, respectively.
  • DREAMS-2: the phase 3 type 2 diabetes trial comparing mazdutide with 1.5 mg dulaglutide over 28 weeks.
  • Dulaglutide: an approved once-weekly GLP-1 receptor agonist, used as the active comparator in two mazdutide diabetes trials.
  • Adverse event (AE): any unwanted medical occurrence during a trial, related to the drug or not; placebo groups report them too.
  • COA (certificate of analysis): the lab document identifying a research vial’s contents; batch-matched or it proves nothing.

References