Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial
Abstract
Background: Zenagamtide (formerly amycretin) is a unimolecular agonist of GLP-1, amylin, and calcitonin receptors. We aimed to investigate the dose-response relationship with respect to the efficacy and safety of once-weekly subcutaneous zenagamtide compared with placebo in adults with type 2 diabetes.
Methods: This 36-week, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial was conducted at 83 hospital and clinic sites across 11 countries. The trial consisted of a 3-week screening period, a 36-week intervention period, and a 4-week follow-up period. Adults (aged 18-75 years) with type 2 diabetes (glycated haemoglobin [HbA1c] 7·0-10·0% [53-86 mmol/mol]), treated with stable doses of metformin with or without a SGLT2 inhibitor, and with a BMI of 23·0 to 2 were randomly assigned (6:1) to once-weekly subcutaneous zenagamtide or placebo using a randomisation and trial supplies management system, before being further randomly assigned to one of six dose groups (1:1:1:1:1:1; 0·4, 1·5, 5, 10, 20, or 40 mg). Participants assigned to placebo were similarly allocated to matched placebo regimens corresponding to each dosing schedule. Randomisation was stratified by HbA1c (1c from baseline to week 36. The primary outcome was assessed in all randomly assigned participants using the efficacy estimand based on on-treatment data without rescue medication. Safety outcomes were assessed in all randomly assigned participants exposed to treatment. The trial is…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 915 participants or records.
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