News · Heart & Metabolic
Mazdutide took off 16.7% of body weight in a phase 3 trial
A JAMA phase 3 trial of 461 Chinese adults with obesity found the dual glucagon and GLP-1 drug mazdutide cut body weight by 16.65% over 60 weeks against 1.50% on placebo.
Based on a peer-reviewed randomized trial in JAMA
- A double-blind, placebo-controlled phase 3 trial at 27 hospitals in China, published in JAMA.
- 461 adults with obesity received treatment, 307 on mazdutide and 154 on placebo, randomized 2 to 1.
- Mazdutide is a once-weekly glucagon and GLP-1 receptor dual agonist, so it works on two receptors rather than one.
- At week 60, mean weight change was -16.65% on mazdutide against -1.50% on placebo.
- That is a between-group difference of about 15 percentage points.
- Participants were younger than in most Western obesity trials: mean age 33.9, mean weight 94.0 kg.
- 16.1% had type 2 diabetes, and 64.0% were female.
- All participants also received a reduced calorie diet and increased physical activity, so the drug was tested as an addition to lifestyle change.
The obesity drug field has moved from hitting one receptor to hitting two, and the numbers have climbed with each addition. A phase 3 trial in JAMA, published by the American Medical Association, tested a version that pairs GLP-1 with glucagon.
At week 60, the mean percentage change in body weight from baseline was -16.65% in the mazdutide group compared with -1.50% in the placebo group.
Why a second receptor
The drug is described by its targets. Mazdutide is a once-weekly glucagon and glucagon-like peptide-1 receptor dual agonist.
GLP-1 is the familiar half, working largely through appetite and gastric emptying. Glucagon is the less familiar one, and is involved in energy expenditure rather than intake. Combining them is an attempt to work on both sides of the balance at once.
The setting is also part of the point: obesity is a worldwide problem and a major public health issue in China, and most of the large obesity trials to date have enrolled elsewhere.
How the trial was built
The design was a double-blind, placebo-controlled, phase 3, randomized clinical trial including Chinese adults with or without type 2 diabetes, run at 27 hospitals from December 2023 to November 2025.
Participants were randomized in a 2:1 ratio to receive a once weekly, 9-mg dose of mazdutide administered subcutaneously or placebo as an adjunct to a reduced calorie diet and increased physical activity for 60 weeks.
That last clause matters for reading the result. Both arms were dieting and exercising. What the trial measures is what the drug adds on top.
Who was in it
A total of 461 participants received the study treatment, 307 on the drug and 154 on placebo.
The group is younger and lighter than the typical Western obesity trial: 64.0% female, 16.1% with type 2 diabetes, mean age 33.9 years, mean body weight 94.0 kg.
That is worth holding onto. A drug’s percentage effect is not guaranteed to travel unchanged across populations of different age and starting size.
The size of the gap
The headline figure is the difference rather than either arm alone. The mean percentage change in body weight from baseline was -16.65% in the mazdutide group compared with -1.50% in the placebo group, leaving roughly fifteen percentage points between them.
The placebo number is itself informative. A group receiving diet advice, exercise advice and injections lost 1.5% over more than a year, which is a fair summary of how hard the problem is without pharmacology.
What one phase 3 trial cannot show
There is no active comparator. Nothing here ranks mazdutide against semaglutide or tirzepatide, and cross-trial arithmetic between different populations and durations is unreliable.
Sixty weeks is also the whole horizon. Obesity is a lifelong condition, and the questions that matter most - what happens on stopping, what happens over a decade, what the muscle-to-fat split of the loss was - sit outside this window.
What the trial establishes is narrower and still substantial: in this population, at this dose, the dual agonist produced a large and clearly measured difference against placebo.
People also ask
How is mazdutide different from semaglutide or tirzepatide?
It targets a different pair of receptors. Semaglutide acts on the GLP-1 receptor alone; tirzepatide adds GIP. Mazdutide is a glucagon and GLP-1 receptor dual agonist, so its second target is the glucagon receptor, which is involved in energy expenditure as well as appetite. Whether that produces a meaningfully different result in practice needs head-to-head trials, which this is not.
Is 16.65% a lot?
It is in the range the newer dual-target drugs have been reporting, and well above what GLP-1-only drugs achieved in their first trials. But cross-trial comparison is unreliable: this trial ran 60 weeks in a Chinese population with a mean age of 33.9 and a mean starting weight of 94 kg, which differs from the populations most Western trials enrolled.
Does the population limit what this shows?
It qualifies it rather than undermining it. The trial was conducted at 27 hospitals in China and the participants were younger and lighter than in comparable Western trials. Drug response can differ by body size and by population, so the percentage here should not be assumed to transfer unchanged.
Were participants also dieting?
Yes, and this matters for reading the number. The drug was given as an adjunct to a reduced calorie diet and increased physical activity, and so was the placebo. The 15-point gap is therefore what the drug added on top of a lifestyle program, not what it achieved alone.
Is this available?
Approval status varies by country and changes, so that is a question for a clinician or a national regulator rather than for a news article. Phase 3 completion is the evidence step before regulatory decisions, not the same thing as availability.