Amycretin Phase 2 reports weight loss and HbA1c gains in type 2 diabetes

Novo Nordisk announced positive results from a Phase 2 trial testing amycretin, an experimental drug that targets both the GLP-1 and amylin hormone receptors, in people with type 2 diabetes ^[1]. This was the first time amycretin had been tested in this patient group, and the company said the results support moving the drug into late-stage testing ^[1].

The trial enrolled 448 people with type 2 diabetes whose blood sugar was not well controlled by metformin, with or without an SGLT2 inhibitor ^[1]. Participants received either once-weekly injections of amycretin, at six dose levels from 0.4 mg to 40 mg, or once-daily oral amycretin, at three dose levels from 6 mg to 50 mg, for up to 36 weeks ^[1]. About 40% of participants were already on an SGLT2 inhibitor before joining the study, and close to two-thirds of participants across both drug forms were male ^[1].

Starting from an average HbA1c of 7.8%, people on the injected version saw reductions of up to 1.8 percentage points by week 36, assuming full adherence to dosing ^[1]. Up to 89.1% of those participants brought their HbA1c below 7%, and 76.2% got it to 6.5% or lower ^[1]. Those on the oral version, starting from an average HbA1c of 8.0%, saw reductions of up to 1.5 percentage points, with 77.6% reaching below 7% and 62.6% reaching 6.5% or lower ^[1]. People given a placebo saw much smaller changes, improving by 0.2 to 0.4 percentage points depending on the form of the drug ^[1]. Novo Nordisk said all these differences versus placebo were statistically significant ^[1].

On weight, injected amycretin produced average losses of up to 14.5% of body weight, starting from an average of 99.2 kg, compared with 2.6% for placebo ^[1]. The oral version produced losses of up to 10.1%, starting from an average of 101.1 kg, versus 2.5% for placebo ^[1]. At the higher doses, weight loss had not leveled off by week 36 for either form of the drug, meaning further loss might have continued with longer treatment ^[1]. The most common side effects were gastrointestinal and mostly mild to moderate, which the company said was consistent with other drugs in the GLP-1 and amylin class ^[1].

Why it matters for patients

Amycretin is still years away from possible approval, and it is not currently available to patients. But the results point to a drug that combines two hormone pathways already used separately in existing GLP-1 medicines and in amylin-based drugs, which the company frames as a route to greater blood sugar control and weight loss in one product ^[1]. For people with type 2 diabetes who have not gotten to target blood sugar levels on metformin alone, the trial suggests this approach could offer another option in development, alongside currently marketed drugs like Ozempic and Mounjaro, though amycretin itself remains experimental and unapproved ^[1]. The trial also tested both an injectable and a pill form, which could eventually matter for patients who prefer not to use needles, though both forms are still in testing ^[1].

It is not yet known how amycretin's results compare directly with approved drugs, since this trial did not include an active comparator, only a placebo group ^[1]. Side effect rates, long-term safety, and how the drug performs outside of a controlled trial are also not yet established ^[1].

What happens next

Novo Nordisk said it now plans to start a Phase 3 program for amycretin in adults with type 2 diabetes in 2026, as part of what it called an extensive late-stage program across multiple conditions ^[1]. No specific start date or expected completion date for the Phase 3 diabetes studies was given in the announcement ^[1].