This was a randomised, double-blind, placebo-controlled phase 2 trial at 24 US centres. 179 adults without type 2 diabetes, with a body mass index of 30 or more, or 27 to under 30 with a weight-related condition, were assigned to placebo or once-weekly subcutaneous mazdutide at 3 to 6 mg, 10 mg or 16 mg for 48 weeks. Mean age was 47.7 years and 66 per cent were female. The primary endpoint was the percentage change in weight at 32 weeks. Mazdutide is a glucagon and GLP-1 receptor dual agonist, a different mechanism from the GIP and GLP-1 combination that dominates the current market.
At 32 weeks, weight fell by 7.3 per cent on 3 to 6 mg, 15.6 per cent on 10 mg and 18.1 per cent on 16 mg, against 0.9 per cent on placebo. Differences from placebo ranged from 6.5 to 17.2 percentage points, all with p below 0.0001, and weight continued to fall to 48 weeks. Adverse events were mostly gastrointestinal and mostly mild to moderate, but discontinuation because of them was highest at 16 mg, at 20 per cent.
There is nothing to do with this today, and that is worth saying plainly: 179 people, phase 2, no participants with type 2 diabetes and no cardiovascular outcome data. What it establishes is that adding glucagon receptor agonism to GLP-1 produces weight loss in the same range as the best current agents, and that the dose which achieves it costs one in five patients their treatment. The drug is already approved in China, so patients may raise it before any Indian or US phase 3 result exists.
- Nothing to prescribe - this is a phase 2 trial in 179 people without diabetes.
- Note the trade-off: the 16 mg arm gave the most weight loss and the most discontinuations, at 20 per cent.
- Glucagon plus GLP-1 is a distinct mechanism from GIP plus GLP-1, so expect a different metabolic and side-effect profile.
- Patients asking about a weight-loss injection approved in China are usually asking about this drug.
- Wait for phase 3 and for data in people with type 2 diabetes before comparing it with tirzepatide.
The statistics, in plain English
The weight figures are reported with standard errors rather than confidence intervals, so a figure like 18.1 per cent plus or minus 1.0 means the true average for this population is very likely within about two percentage points either side - the effect is large and the uncertainty around it is small. The very low p values are unsurprising given a placebo group that lost under 1 per cent; when the gap is this wide, statistical significance is never the interesting question. What phase 2 cannot tell you is how the drug behaves in the people you actually treat: everyone here was free of type 2 diabetes, and 179 participants is far too few to detect uncommon harms.
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