Mazdutide vs Retatrutide: How the Dual and Triple Agonists Compare

The two molecules share the GLP-1 and glucagon receptor arms. Retatrutide adds a third, the GIP receptor, at which its discovery paper reported stronger activity than at the other two. Mazdutide is therefore a dual agonist and retatrutide a triple agonist, and the GIP arm is the structural difference between them.^[1][7]

The glucagon arm is what both compounds have in common. Reviews describe glucagon as stimulating lipolysis and fat oxidation in the liver, reducing calorie intake and raising energy expenditure, the last shown at least in animal models. Because glucagon also raises blood glucose, glucagon-based compounds pair it with GLP-1 receptor activity; mazdutide, survodutide and retatrutide all follow that logic, and how chronic glucagon-receptor activation behaves in humans is still being worked out.^[13]

What the GIP arm adds on top is a question the available comparisons cannot settle, because they are indirect. A 2026 BMJ network meta-analysis placed mazdutide and retatrutide among emerging agents that may produce weight reductions similar to or greater than established drugs, and rated the certainty of that evidence as very low to low.^[15]

In GLORY-1, published in the New England Journal of Medicine in 2025, 610 Chinese adults with a BMI of at least 28, or 24 to 28 with a weight-related condition, received weekly mazdutide at 4 or 6 mg or placebo for 48 weeks. Mean body weight changed by −11.00% and −14.01% at week 48, against +0.30% with placebo, and 35.7% and 49.5% of participants reached a reduction of at least 15%, against 2.0%.^[2]

GLORY-2 (JAMA, 2026) tested a higher 9 mg dose in 461 Chinese adults with a BMI of at least 30 for 60 weeks. Body weight fell by 16.65%, against 1.50% with placebo. Gastrointestinal effects were frequent: vomiting was reported in 53.1% of the mazdutide group, nausea in 46.9% and diarrhoea in 39.4%, mostly mild to moderate.^[3]

In type 2 diabetes, two phase 3 trials published in Nature in 2026 reported HbA1c reductions against placebo at 24 weeks (DREAMS-1) and superiority over dulaglutide 1.5 mg at 28 weeks, with greater weight loss than dulaglutide (DREAMS-2). Outside China, a 179-person US phase 2 trial reported 32-week weight changes of −7.3%, −15.6% and −18.1% in its 3–6 mg, 10 mg and 16 mg groups, against −0.9% with placebo; 20% of the 16 mg group stopped treatment because of adverse events.^[4][5][6]

Retatrutide's obesity data come from a 48-week phase 2 trial of 338 adults without diabetes, in which mean body weight fell by up to 24.2% against 2.1% with placebo. Its first peer-reviewed phase 3 trial, TRANSCEND-T2D-1, reported weight reductions of up to 15.3% at 40 weeks in people with type 2 diabetes.^[8][9]

Setting those numbers beside mazdutide's is tempting and mostly misleading. The trials differ in population (GLORY-1 enrolled Chinese adults from a BMI of 28, or 24 with a weight-related condition; the retatrutide phase 2 trial started at 30, or 27 with a condition), in duration (48 to 60 weeks) and in phase. The network meta-analysis that compared them indirectly rated the certainty of the evidence for both as very low to low.^{[2][3][8][15]}

The fair summary is about evidence shape rather than size. Mazdutide has regulatory approval in China and several published phase 3 trials; retatrutide has the three-receptor design and, so far, one published phase 3 trial. Neither record answers which molecule does more in the same population.^[1][9]

Survodutide (BI 456906) is the other GLP-1/glucagon dual agonist with published phase 3 data. In a 46-week phase 2 dose-finding trial of 387 adults without diabetes, body weight fell by 6.2% to 14.9% across the four doses, against 2.8% with placebo, and gastrointestinal adverse events occurred in 75% of participants on survodutide against 42% on placebo.^[10]

In the phase 3 SYNCHRONIZE-1 trial (New England Journal of Medicine, 2026), 725 adults with obesity and without diabetes lost 12.2% and 13.0% of body weight at 76 weeks on the two doses, against 5.4% with placebo; gastrointestinal events occurred in 80.9% and 89.7% of participants, against 47.9%. A separate phase 2 trial in biopsy-confirmed MASH with fibrosis reported improvement in MASH without worsening of fibrosis in 43% to 62% of participants on survodutide, against 14% on placebo.^[12][11]

Across the mazdutide, survodutide and retatrutide trials, gastrointestinal effects were the most common adverse events, mostly mild to moderate and more frequent at higher doses. Discontinuation because of adverse events ranged widely, from 0.5–1.5% across the arms of GLORY-1 to 20% in the 16 mg group of the US mazdutide phase 2 trial.^{[2][6][12][8]}

Heart rate is the signal reviewers watch most closely with glucagon co-agonism. A 2026 review found that mazdutide and survodutide generally raised heart rate to a similar extent as GLP-1 receptor agonists, but noted that at least one other dual agonist was discontinued partly because of large heart-rate increases and QT prolongation. In the retatrutide phase 2 trial, heart rate rose in a dose-dependent way and peaked at 24 weeks. The review concluded that cardiovascular effects must be clarified compound by compound in ongoing trials, including a cardiovascular-outcome trial of survodutide.^[14][8]

No. As of September 2026, the European Medicines Agency's database of authorised medicines lists no product containing mazdutide, survodutide or retatrutide. Mazdutide's first approvals came in China in 2025, for weight management and then for type 2 diabetes; retatrutide is still described in the 2026 literature as under clinical development.^[16][1][9]

Peptyds supplies retatrutide, tirzepatide and semaglutide as lyophilised research peptides for in-vitro laboratory work only, with batch documentation described on the quality page. It does not supply mazdutide or survodutide. None of these research products is a medicine, and none is intended for human use.