Phase 2 zenagamtide trial reports HbA1c reductions across six weekly doses

What happened

A phase 2 trial found that once-weekly injectable zenagamtide reduced HbA1c more than placebo across six tested maintenance doses in adults with type 2 diabetes. Zenagamtide, formerly called amycretin, is one investigational molecule that targets the GLP-1, amylin, and calcitonin receptor systems.

The 36-week randomized, double-blind trial enrolled 262 adults through 83 clinical sites spread across 11 countries. Every participant used a stable metformin dose, and some also used an SGLT2 inhibitor. Entry HbA1c ranged from 7.0% to 10.0%. The study assigned 225 people to zenagamtide and 37 to placebo. Zenagamtide maintenance doses ranged from 0.4 mg to 40 mg, after dose escalation from a 0.2 mg starting dose.

Average HbA1c at baseline was 7.8%. By week 36, the estimated reduction ranged from 0.9 percentage points with the 0.4 mg dose to 1.7 points with the 40 mg dose. Each of the six dose comparisons favored zenagamtide over its matched placebo comparison and met the study's statistical threshold.

Most adverse events involved the digestive system and were described as mild or moderate. Twenty-one of the 261 treated participants had a serious adverse event, including 18 participants across the six zenagamtide groups and three who received placebo. None of the participants died during the reported study period.

What it means

Researchers now have randomized dose-ranging evidence that subcutaneous zenagamtide has glucose-lowering activity in people with type 2 diabetes. Testing six maintenance doses helps them assess how response and tolerability change with dose and can guide the regimens selected for later trials.

The study's primary endpoint was measured while participants were on treatment and before rescue medication. That makes the result specific to glucose control under the trial protocol, rather than a general estimate of every outcome after treatment assignment.

What it does not mean

The investigators designed this study around diabetes and HbA1c, not around proving efficacy for obesity treatment. No body-weight results appear in the PubMed abstract. An HbA1c reduction over 36 weeks also does not prove fewer heart attacks, kidney complications, deaths, or other long-term outcomes.

The trial cannot establish long-term or uncommon safety risks. It was relatively small, follow-up was brief, and the abstract does not give a full account of serious events, discontinuations, or adverse events at every dose.

Zenagamtide remains investigational. Novo Nordisk funded the trial, and several authors were company employees and shareholders or reported other industry relationships. The findings should be read as phase 2 evidence, not as an approval or a treatment recommendation.