Therapeutic: mazdutide for obesity

Published: 6-Feb-2024

Obesity is associated with a wide variety of other conditions and there has been significant interest in the use of diabetic treatments, such as those targeting the glucagon-like peptide-1 (GLP-1) receptor, to assist with weight loss

Another such drug is being developed in China by Innovent in a licence agreement with Eli Lilly.

In contrast to the existing drugs in this class that just affect GLP-1 receptors, it is a dual agonist that also targets the glucagon receptor.

In a Phase II randomised controlled trial, 248 subjects who were overweight with comorbidities or obese were given 3, 4.5 or 6 mg of the drug or a placebo once a week for 24 weeks.

Mean percentage declines in weight from baseline were 6.7%, 10.4% and 11.3%, respectively, with the drug and 1.0% with the placebo.1

All dose levels were well tolerated with the most common adverse events being diarrhoea, nausea and upper respiratory tract infections. The company has also announced positive results of a Phase III trial.

The multicentre, randomised, double-blind, placebo-controlled trial was designed to evaluate the drug’s efficacy and safety in a group of 610 overweight or obese Chinese adults.

Subjects were given 4 or 6 mg of mazdutide or a placebo throughout the 48-week trial period. Both doses were superior to the placebo in terms of percentage change in body weight from baseline to week 32 and the proportion of participants with weight loss of at least 5% at that point.

Efficacy improved further between weeks 32 and 48. All key secondary endpoints were also met. Its ability to treat type 2 diabetes is also being evaluated.

A randomised, placebo-controlled Phase Ib study has been done with 42 patients in three cohorts and randomised to receive once weekly subcutaneous doses of 3, 4.5 or 6 mg of mazdutide, 1.5 mg of dulaglutide or a placebo.2

There were reductions from baseline in glycated haemoglobin A1c (HbA1c), fasting plasma glucose and post-mixed-meal tolerance test glucose levels in patients who were given mazdutide; the most common treatment-emergent adverse events were diarrhoea, a decrease in appetite and nausea.

In a Phase II study, the 250 subjects had type 2 diabetes that was inadequately controlled with diet and exercise alone or with stable metformin.3 They were given 3, 4.5 or 6.0 mg of mazdutide, 1.5 mg of open-label dulaglutide or a placebo subcutaneously for 20 weeks.

Mean falls in HbA1c from baseline ranged from 1.41–1.67% with mazdutide, 1.35% with dulaglutide and 0.03% with the placebo. Mean percentage falls in body weight were dose dependent; they were up to 7.1% with mazdutide, 2.7% with dulaglutide and 1.4% with the placebo.

The most common adverse events with mazdutide were diarrhoea, decreased appetite, nausea, vomiting and hypoglycaemia. Three further Phase III studies are under way, one in obesity and two in type 2 diabetes. The company is now planning to submit the drug for regulatory approval.


  1. L. Ji, et al., Nat. Commun. 14, 8289 (2023).
  2. H. Jiang, et al., Nat. Commun. 13, 3613 (2022).
  3. B. Zhang, et al., Diabetes Care 47, 160 (2024).

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