Amycretin Shows Significant Weight Loss, HbA1c Reductions in Type 2 Diabetes

Amycretin (Novo Nordisk), a unimolecular agonist of glucagon-like peptide 1 (GLP-1) and amylin receptors, induced significant weight loss and hemoglobin A1c (HbA1c) reductions in patients with type 2 diabetes in a phase 2 clinical trial (NNC0487-0111), according to a news release from Novo Nordisk.^1,2

Amycretin Demonstrates Significant HbA1c Reductions

Assuming all patients adhered to treatment, once-weekly subcutaneous amycretin demonstrated dose-dependent reductions in HbA1c of up to –1.8% by week 36 from a mean baseline level of 7.8%. Furthermore, from a mean baseline body weight of 99.2 kg, subcutaneous amycretin elicited significant rates of weight loss of up to –14.5% compared with –2.6% in patients treated with placebo.¹

For oral amycretin, among treated patients—who reported a mean baseline HbA1c of 8.0%—there were dose-dependent HbA1c improvements of up to –1.5% by week 36. Proportions of patients achieving HbA1c levels of less than 7% and 6.5% or less with once-daily oral amycretin were 77.6% and 62.6%, respectively. Comparatively, patients treated with placebo reported HbA1c improvements of –0.2% and –0.4% with subcutaneous and oral amycretin, respectively.¹

Oral amycretin elicited statistically significant weight loss of –10.1% from a mean baseline body weight of 101.1 kg, compared with –2.5% in individuals treated with placebo. There was no weight loss plateau observed at week 36 for patients using higher doses of amycretin, irrespective of administration route, a key indicator of sustained effectiveness.¹

Both subcutaneous and oral amycretin demonstrated a safe and well-tolerated profile consistent with those of alternative amylin and incretin-based therapies. Common adverse events reported with amycretin were gastrointestinal in nature, but the majority were mild to moderate in severity, according to the study investigators.¹

“We are very encouraged by the phase 2 data with amycretin in people with type 2 diabetes—the first time amycretin has been evaluated in this population. The data further validate the potential best-in-class profile of amycretin,” Martin Holst Lange, chief scientific officer and executive vice president of research and development at Novo Nordisk, said in the news release. “Amycretin is built on the complementary biology of GLP-1 and amylin, and we are looking forward to bringing amycretin into an extensive phase 3 development program across multiple indications in 2026.”¹

Enrollment Details of the Current Trial

The phase 2 T2D trial was an interventional, multinational, multi-center, randomized, parallel, double-blind, placebo-controlled, dose-finding study. Enrolled patients had inadequately controlled T2D—indicated by HbA1c levels of 7.0% to 10.0%—and were on a stable dose of metformin with or without prescribed sodium-glucose contransporter 2 (SGLT2) inhibitors.¹

Nine active treatment arms comprised the study, including patients receiving increasing doses of once-weekly subcutaneous amycretin (6 groups: 0.4 mg, 1.5 mg, 5 mg, 10 mg, 20 mg, and 40 mg) and oral amycretin (3 groups: 6 mg, 25 mg, and 50 mg) for up to 36 weeks. Investigators primarily sought to characterize the dose-response relationship of subcutaneous and oral amycretin on change in HbA1c from baseline to week 36 in participants with T2D. A total of 448 patients were enrolled.¹

Past Data and the Pharmacist’s Role

Prior results from a phase 1b/2a clinical trial of amycretin demonstrated promising reductions in body weight in patients with overweight or obesity at a series of benchmarks. In the trial, amycretin demonstrated an estimated weight loss of 9.7% at 20 weeks on a 1.25-mg dose, 16.2% at 28 weeks on a 5-mg dose, and 22% at 36 weeks on a 20-mg dose. Like the current trial, gastrointestinal events were the main safety concern observed by investigators, and they were mild to moderate in nature.³

Pharmacists, who have a growing presence in weight management and diabetes care, should follow the developments of amycretin and educate themselves in preparation for its possible availability in the future. Amycretin could serve as an effective and convenient treatment option for patients struggling with HbA1c or weight loss reductions across numerous disease states.^1,3

REFERENCES

1. Novo Nordisk phase 2 trial with amycretin reports significant weight loss and HbA1c reduction in type 2 diabetes. News release. Novo Nordisk. Released November 25, 2025. Accessed December 1, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916463

2. A research study comparing how well different doses of the medicine NNC0487-0111 lower blood sugar in people with type 2 diabetes. ClinicalTrials.gov identifier: NCT06542874. Last Updated October 20, 2025. Accessed December 1, 2025. https://clinicaltrials.gov/study/NCT06542874?term=NNC0487-0111&rank=6

3. Gallagher A. Novo Nordisk announces top-line results for amycretin as potential obesity, overweight treatment. Pharmacy Times. Published February 3, 2025. Accessed December 1, 2025.