Mazdutide vs Semaglutide

What is being compared?

Mazdutide (IBI362; LY3305677) is a dual GLP-1 and glucagon receptor agonist. Semaglutide is a GLP-1 receptor agonist used in distinct regulated products. Receptor differences are a mechanism description, not proof that one treatment has greater clinical benefit. The comparison below keeps the trial drug, population, endpoint and regulatory jurisdiction attached to each claim. Mazdutide US phase 2, PMID 42628555 · FDA Wegovy label

The regulatory row is supported by Innovent’s Hong Kong exchange filing, the FDA letter concerning one US mazdutide seller, and the distinct Ozempic, Rybelsus/Ozempic tablet, and Wegovy FDA labels. The FDA letter identifies that seller’s mazdutide products as unapproved new drugs; it is not a global approval record.

Weight evidence without a cross-trial ranking

GLORY-1 was a placebo-controlled phase 3 trial in Chinese adults with obesity or overweight, with 48 weeks of treatment and a primary weight endpoint at week 32. GLORY-2 was a separate Chinese phase 3 trial in adults with obesity, including some with type 2 diabetes. At week 60, GLORY-2 reported mean weight changes of -16.65% with mazdutide 9 mg and -1.50% with placebo. Its stated efficacy analysis included participants who received study treatment. The published US phase 2 study enrolled 179 adults with obesity or overweight without type 2 diabetes and reported 32-week weight results under an efficacy or hypothetical estimand. Those US results do not automatically reproduce the Chinese phase 3 findings. GLORY-1, PMID 40421736 · GLORY-2, PMID 42251595 · US phase 2, PMID 42628555

STEP 1 randomized 1,961 adults with overweight or obesity without diabetes to semaglutide 2.4 mg injection or placebo and reported 68-week mean weight reductions of 14.9% and 2.4%, respectively, under the primary treatment-policy estimand, regardless of treatment discontinuation or rescue intervention. This is a within-STEP-1 comparison, just as the GLORY-2 figures compare its own randomized groups. Different entry criteria, durations, products and analysis methods make a subtraction between GLORY-2 and STEP 1 an unsupported head-to-head estimate. STEP 1, PMID 33567185 · GLORY-2, PMID 42251595

Diabetes evidence and the limited direct comparison

Published Chinese mazdutide trials report HbA1c outcomes against placebo in DREAMS-1 and against dulaglutide in DREAMS-2. These are distinct populations and comparators, and neither is a semaglutide comparison. DREAMS-1, PMID 41407859 · DREAMS-2, PMID 41407860

A June 2026 conference abstract for the open-label DREAMS-3 trial reports a direct comparison in 349 selected Chinese adults with early type 2 diabetes and obesity. Its 32-week endpoint was the proportion reaching both HbA1c below 7% and at least 10% weight loss. The abstract reports superiority for mazdutide versus semaglutide 1 mg on that composite and more nausea and vomiting with mazdutide. This abstract-only, comparator-specific result cannot be recast as a general weight-loss, safety or product superiority claim; a full results paper was not identified in the bounded source review. DREAMS-3 abstract, DOI 10.2337/db26-1226-OR

Product approvals and outcome limits

Innovent reports Chinese NMPA approval of mazdutide for adult chronic weight-management and type 2 diabetes indications subject to criteria in its filing. This is sponsor-reported here; the bounded review did not obtain an independent Chinese product label. No FDA approval for mazdutide was verified. The FDA warning letter concerns products sold by a named US seller and should not be stretched into a finding about every jurisdiction. Innovent filing · FDA warning letter

Semaglutide’s US status depends on the specific product and indication. Ozempic and Rybelsus have type 2 diabetes indications. Wegovy has labeled weight and selected cardiovascular risk-reduction uses. Wegovy injection also has accelerated approval for adults with noncirrhotic MASH and F2-F3 fibrosis based on histologic endpoints; continued approval may depend on confirmatory clinical benefit. This MASH indication does not extend to Wegovy tablets or to all semaglutide products. The separate SELECT trial measured cardiovascular events in adults with overweight or obesity, established cardiovascular disease and no diabetes; the cited mazdutide weight trials do not supply an equivalent cardiovascular-outcomes comparison. FDA Ozempic label · FDA Rybelsus/Ozempic tablet label · FDA Wegovy label · SELECT, PMID 37952131

Gastrointestinal adverse events were reported in the cited weight and DREAMS-3 studies, but rates and discontinuations cannot be ranked across different trials and products. No combination-safety or efficacy conclusion for mazdutide plus semaglutide follows from these separate studies. GLORY-2, PMID 42251595 · STEP 1, PMID 33567185 · DREAMS-3 abstract

This comparison is educational research context, not medical advice or a treatment protocol.