Mazdutide (IBI362): GLP-1/Glucagon Dual Agonist Weight-Loss Evidence

Mazdutide (development codes IBI362 and LY3305677) is a once-weekly injectable that activates two receptors at once: the GLP-1 receptor and the glucagon receptor. That second target is what sets it apart from semaglutide and from tirzepatide — adding glucagon agonism is meant to raise energy expenditure and reduce liver fat on top of the appetite suppression GLP-1 drugs already deliver. The molecule is based on the gut hormone oxyntomodulin and was developed by Innovent Biologics in China under license from Eli Lilly. In June 2025 it became one of the first GLP-1/glucagon dual agonists anywhere to win regulatory approval, when China's National Medical Products Administration (NMPA) cleared it for chronic weight management. It is not FDA-approved in the United States. This article covers what mazdutide is, what the phase 3 GLORY-1 trial actually showed, how its weight-loss magnitude compares to the approved drugs, and what its approval means for patients outside China.

The honest summary

• Mazdutide is a GLP-1 + glucagon dual agonist. A single peptide based on oxyntomodulin activates both the GLP-1 receptor (appetite suppression, slowed gastric emptying, glucose-dependent insulin release) and the glucagon receptor (increased energy expenditure and hepatic fat mobilization). It is dosed once weekly by subcutaneous injection (Ji 2022 EClinicalMedicine^[3], Jiang 2022 Nat Commun^[4]).
• Approved in China, not in the US. The NMPA approved mazdutide for chronic weight management in June 2025, making it one of the first GLP-1/glucagon dual agonists approved for obesity anywhere. As of 2026 it has no FDA approval and is not legally marketed in the United States.
• GLORY-1 is the pivotal evidence. The phase 3 GLORY-1 trial (Ji 2025 NEJM^[1]) randomized 610 Chinese adults with obesity or overweight to mazdutide 4 mg, 6 mg, or placebo. At week 48 the mean body-weight change was −11.0% on 4 mg and −14.0% on 6 mg versus +0.3% on placebo.
• Magnitude lands between semaglutide and tirzepatide. GLORY-1's 6 mg result (−14.0% at 48 weeks) is broadly in the range of semaglutide's STEP-1 (−14.9% at 68 weeks, Wilding 2021^[5]) and below tirzepatide's SURMOUNT-1 top dose (−20.9% at 72 weeks, Jastreboff 2022^[6]) — though cross-trial comparison is imperfect given different populations and timepoints.
• It has dual-agonist class siblings. Survodutide (Boehringer Ingelheim/Zealand) and pemvidutide (Altimmune) are also GLP-1/glucagon dual agonists in development, while retatrutide (Lilly) adds a third target (GIP) on top of GLP-1 and glucagon. Mazdutide is the first of this glucagon-containing family to reach the market.

What mazdutide actually is, pharmacologically

Mazdutide is a long-acting peptide engineered from oxyntomodulin, a naturally occurring gut hormone released from the intestine after meals that itself activates both the GLP-1 and glucagon receptors. By optimizing that native dual activity into a once-weekly drug, mazdutide combines two mechanisms that pull weight down through partly different levers. The GLP-1 receptor side shares its core action with semaglutide and liraglutide: glucose-dependent insulin secretion, glucagon suppression at the islet level, delayed gastric emptying, and hypothalamic satiety signaling. The glucagon receptor side — the part that distinguishes mazdutide from a pure GLP-1 drug — increases resting energy expenditure and promotes hepatic fat oxidation and lipolysis.

The pairing is deliberately counterintuitive. Glucagon is best known as the hormone that raises blood sugar, so adding glucagon agonism to a diabetes-adjacent drug seems backwards. The rationale is that the GLP-1 component's insulin-secreting and appetite-suppressing effects offset glucagon's glycemic downside, while glucagon's thermogenic and hepatic effects add weight loss and liver-fat reduction that GLP-1 alone delivers less of. This is the same engineering logic behind survodutide, pemvidutide, and the glucagon arm of retatrutide's triple agonism.

The pivotal phase 3 trial: GLORY-1

GLORY-1 (Ji 2025 NEJM^[1]) is the registration trial behind the China approval. It was a randomized, double-blind, placebo-controlled phase 3 study in 610 Chinese adults with obesity or overweight (mean baseline body weight about 87 kg, mean BMI about 31). Participants received once-weekly subcutaneous mazdutide 4 mg, 6 mg, or placebo. The co-primary endpoints were percent change in body weight and the proportion achieving at least 5% weight loss at week 32, with body-weight change at week 48 assessed as a key secondary endpoint.

At week 32, mean body-weight change was −10.09% on 4 mg and −12.55% on 6 mg, versus +0.45% on placebo. By week 48 the curves had continued downward: −11.00% on 4 mg and −14.01% on 6 mg, versus +0.30% on placebo. The proportions of participants reaching the 5%, 10%, and 15% weight-loss thresholds rose accordingly, and the trial reported improvements in waist circumference, blood pressure, lipids, and liver enzymes consistent with the dual mechanism. Adverse events were dominated by gastrointestinal symptoms (nausea, diarrhea, vomiting, decreased appetite) typical of incretin drugs, most pronounced during dose escalation.

The earlier dose-finding evidence

Before GLORY-1, mazdutide (then almost always referred to as IBI362) was studied in a series of early-phase trials in Chinese adults. A phase 1b multiple-ascending-dose study in overweight or obese adults (Ji 2022 EClinicalMedicine^[3]) tested 9 mg and 10 mg titration regimens over 12–16 weeks and reported roughly −11.7% body weight on the 9 mg regimen versus −1.8% on placebo — an early signal that dual GLP-1/glucagon agonism could produce double-digit weight loss. A separate phase 1b study in patients with type 2 diabetes (Jiang 2022 Nat Commun^[4]) confirmed the IBI362 / LY3305677 identity and the dual-receptor pharmacology, and a phase 2 trial in Chinese patients with type 2 diabetes (Zhang 2024 Diabetes Care^[2]) established glycemic efficacy and the dose range that GLORY-1 later carried into phase 3.

The through-line across these trials is that the doses are lower than the early ascending-dose work might suggest: GLORY-1 settled on 4 mg and 6 mg rather than the 9–10 mg explored in the first dose-finding study, reflecting the usual tradeoff between efficacy and gastrointestinal tolerability that defines the entire incretin class.

Magnitude: mazdutide vs the approved and pipeline drugs

The fair reading is that mazdutide's 6 mg arm at 48 weeks (−14.0%) sits in the semaglutide range and below tirzepatide's top dose. But two caveats matter. First, GLORY-1 ran 48 weeks while STEP-1 and SURMOUNT-1 ran 68–72 weeks, so mazdutide's number is from a shorter exposure. Second, GLORY-1 enrolled Chinese adults with a lower mean baseline BMI (~31) than the global obesity trials, and baseline BMI influences percent weight loss. Cross-trial comparisons like this are directional, not definitive.

The glucagon angle: energy expenditure and liver fat

The clinical interest in glucagon agonism is not really about appetite — GLP-1 already handles that. It is about the two things glucagon adds: a modest increase in energy expenditure, and direct mobilization of fat from the liver. That makes the GLP-1/glucagon dual class of particular interest for metabolic dysfunction-associated steatotic liver disease (MASLD/MASH), where reducing hepatic fat is the therapeutic goal. Survodutide, mazdutide's closest pipeline sibling, has shown promising phase 2 results in MASH for exactly this reason. Mazdutide's own trials have reported favorable shifts in liver enzymes, consistent with the mechanism, though the headline obesity approval rests on weight outcomes rather than a dedicated liver-disease indication.

What the China approval means — and does not mean — for US patients

China's NMPA approval of mazdutide in June 2025 is genuinely notable: it is one of the first regulatory approvals worldwide for a GLP-1/glucagon dual agonist in obesity, and it validates the mechanism beyond the pure-GLP-1 and GLP-1/GIP classes. But a China approval does not translate to availability in the United States. Mazdutide has no FDA approval, is not legally sold or compounded in the US, and is not the same regulatory product as anything Americans can be prescribed today. A US-directed development and approval pathway would require its own trials and FDA review, which had not produced an approval as of 2026.

The practical takeaway for someone in the US researching mazdutide is that the relevant, prescribable options remain the approved drugs: semaglutide (Wegovy/Ozempic, STEP-1^[5]) and tirzepatide (Zepbound/Mounjaro, SURMOUNT-1^[6]). Anything marketed as “mazdutide” through US research-peptide channels is operating outside any approved supply chain and carries the identity, purity, and dosing risks that come with unregulated peptides. The honest answer to “can I get mazdutide in the US?” in 2026 is: not legitimately. Talk to a clinician about the approved drugs instead.

Related research

• GLP-1 pipeline overview — the broader landscape including survodutide, mazdutide's closest GLP-1/glucagon sibling, plus maridebart-cafraglutide and ecnoglutide
• Retatrutide triple-agonist evidence — Lilly's GLP-1/GIP/glucagon agonist, which adds the same glucagon target on top of a third receptor
• Amycretin pipeline evidence — Novo Nordisk's unimolecular GLP-1/amylin dual agonist, a different two-receptor strategy
• CagriSema REDEFINE trial results — the GLP-1/amylin co-formulation, for contrast with the glucagon-based dual class
• Wegovy (semaglutide 2.4 mg) — the STEP-1 reference standard for new obesity drugs
• Zepbound (tirzepatide) — the current best-in-class approved obesity drug

Important disclaimer. Mazdutide is approved in China for chronic weight management but is investigational and not FDA-approved in the United States as of 2026. The data summarized here come from the GLORY-1 phase 3 trial and earlier-phase studies conducted primarily in Chinese adults; cross-trial comparisons to semaglutide and tirzepatide are directional, not head-to-head. This article is educational and does not constitute medical advice or an endorsement to use any unapproved or compounded product marketed as “mazdutide.” All PMIDs were verified live against the PubMed E-utilities API on 2026-06-01.

Last verified: 2026-06-01. Next review: every 6 months, or sooner if mazdutide enters US (FDA) review, if Innovent or Eli Lilly publish additional GLORY-program readouts, or if a head-to-head trial against semaglutide or tirzepatide is registered.