Mazdutide

1. 01Skin

   A weekly injection under the skin

   In trials and in its Chinese approval, mazdutide is injected under the skin once a week. It moves slowly from there into the blood, reaching its highest level about three days later.

   For experts

   Mazdutide is administered subcutaneously once weekly. In the phase 1b multiple-ascending-dose study in Chinese adults with overweight or obesity, median Tmax was 72 hours (range 11.8 to 120 hours), consistent with slow absorption from the subcutaneous depot.[src]

2. 02Bloodstream

   A fatty tail keeps it in the body for days

   Mazdutide is based on a natural gut hormone called oxyntomodulin. It has a small fatty chain added to it, which helps it stay in the body much longer. Its half-life is about one to two weeks, so one shot a week is enough.

   For experts

   Mazdutide is described as a long-acting synthetic analogue of mammalian oxyntomodulin with a fatty-acyl moiety to extend half-life. The PubChem record shows a C20 diacid-gamma-Glu-2xOEG chain on Lys20 and Aib at position 2. In the phase 1b study the terminal half-life was 150.9 to 403.5 hours (6.3 to 16.8 days).[src][src]

3. 03Pancreas

   Switches on GLP-1 receptors that help release insulin

   One half of mazdutide acts like GLP-1. This helps the pancreas release insulin when blood sugar is high. In people with type 2 diabetes in China, average blood sugar over three months fell clearly compared with placebo.

   For experts

   GLP-1 receptor agonism enhances glucose-dependent insulin secretion. In DREAMS-1 (n=320, type 2 diabetes, monotherapy), HbA1c fell by 1.57% and 2.15% at week 24 in the two mazdutide arms versus 0.14% with placebo (both P<0.0001). In DREAMS-2 (n=731, on background oral therapy), both mazdutide arms were superior to dulaglutide for HbA1c (treatment differences of -0.24% and -0.30%). Effects on beta-cell function in humans specifically were not established in the sources reviewed.[src][src][src]

4. 04Brain

   Lowers appetite through GLP-1 signalling

   GLP-1 also acts on the brain and gut to make people feel full sooner and eat less. People taking mazdutide in trials often reported decreased appetite, and they lost weight compared with placebo.

   For experts

   GLP-1 receptor agonists reduce food intake through central and gut-brain pathways; this is class-level mechanistic knowledge rather than a mazdutide-specific measurement. Decreased appetite was among the most common adverse events in the phase 1b trial and in DREAMS-1 (type 2 diabetes). In GLORY-1 the mean change in body weight at week 48 was -11.00% and -14.01% in the two mazdutide arms versus +0.30% with placebo (treatment-policy estimand, n=610).[src][src][src][src]

5. 05Liver

   Glucagon activity may help the liver burn and clear fat

   The other half of mazdutide acts like glucagon, which mostly works on the liver. Scientists think this helps the body use up fat and energy. In the GLORY-1 trial, the company reported that people who started with a lot of liver fat ended up with much less. Mouse studies also point to the liver as a target.

   For experts

   GCGR is expressed mainly in liver and kidney. Preclinical evidence suggests glucagon signalling increases hepatic lipolysis and fat oxidation and raises energy expenditure, but reviews stress that these pathways have been shown mainly in animals and are not yet delineated in humans. Human data on liver fat exist: in GLORY-1 participants with baseline liver fat of 10% or more, the company reported mean liver-fat changes of -65.85% and -80.24% at week 48 versus -5.27% with placebo. In a high-fat-diet mouse model of MASLD and in cultured liver cells (animal and cell data only, not human), mazdutide reduced hepatic steatosis and ER-stress and inflammatory signalling.[src][src][src][src]

6. 06Fat tissue

   Body weight falls over months

   Over months, people in the trials lost a meaningful share of their body weight compared with placebo. The size of the loss depended on the treatment level, and results come mostly from adults in China.

   For experts

   Weight loss was dose-dependent across trials. In the higher-dose GLORY-2 phase 3 trial (n=461, BMI 30 or more, 60 weeks) the mean change was -16.65% versus -1.50% with placebo. In the US phase 2 trial (n=179) the least-squares mean change at week 32 (efficacy estimand) was -7.3%, -15.6% and -18.1% across three mazdutide regimens versus -0.9% with placebo. Whether the glucagon component adds energy expenditure in humans beyond what GLP-1 agonism does has not been isolated in the sources reviewed.[src][src][src]

7. 07Heart

   Heart rate and blood pressure are watched closely

   Glucagon can speed up the heart in high doses, so doctors watch this. In trials, mazdutide raised heart rate about as much as other GLP-1 drugs while blood pressure went down. Long-term heart safety has not yet been shown.

   For experts

   Clinical studies of GCGR/GLP-1R dual agonists including mazdutide have generally found heart-rate increases similar to GLP-1 receptor monoagonists, together with reduced blood pressure; unequivocal evidence of GCGR expression in the human heart is lacking. A 2026 meta-analysis noted that longer-term, multi-ethnic studies are needed to confirm cardiovascular safety. Three participants in the phase 1b study had asymptomatic ECG abnormalities.[src][src][src]

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