Subcutaneous Amycretin Shows Weight Loss of 9.7% for 20 Weeks

Amycretin, a unimolecular glucagon-like peptide-1 (GLP-1) and amylin receptor agonist, showed an estimated body weight loss of 9.7% with a 1.25 mg dose (20 weeks), Novo Nordisk announced in a release.¹ In the phase 1b/2a clinical trial, the once weekly subcutaneous drug was evaluated for safety, tolerability, pharmacokinetics, and proof-of-concept.

Amylin medications can help to decrease food intake, slow gastric emptying, and reduce postprandial glucagon release. | Image Credit: Feng Yu | stock.adobe.com

GLP-1 medications have been on the rise to treat type 2 diabetes (T2D) and obesity, with findings to support other therapeutic options such as chronic kidney disease, which semaglutide (Ozempic) has recently been approved for. T2D can inhibit insulin secretion and GLP-1 medications can help to revive this process. Additionally, GLP-1 medications are known to delay gastric emptying and inhibit glucagon production from pancreatic cells. Likewise, the medication class has also shown benefits in cardiac health, such as lowering blood pressure and total cholesterol. Amylin medications, which can also be secreted within insulin, can help to decrease food intake, slow gastric emptying, and reduce postprandial glucagon release. Preclinical models have suggested the amylin could be useful for treating obesity.^2,3

Amycretin is similar to both hormones, therefore, investigators aimed to determine if the drug was safe and how it would affect body weight to improve treatment of overweight, obesity, and related diseases. In the 4-part study, investigators conducted part A in 5 groups, including 8 patients, with 6 randomized to receive a dose of the drug and 2 to receive the placebo. Part B consisted of 3 groups, with 9 individuals receiving the study drug and 3 receiving the placebo for 10 days. The dosing schedule was sequential to evaluate safety concerns that arise in each group. Parts C and D were similar, but patients in part D were treated with a different formulation. Each part consisted of 1 group with 15 patients receiving the active treatment and 4 receiving the placebo for 12 weeks. Both parts C and D were sequential to observe for safety.⁴

Patients were aged 18 to 55 years, with patients in parts A and B having a body mass index (BMI) of 25 to 34.9 kg/m² and parts C and D having a BMI of 27 to 39.9 kg.m². The primary outcome included the number of treatment emergent adverse events, with secondary adverse events evaluating for different plasma concentrations.⁴

In addition to the weight loss on the 1.25 mg dose, investigators found that the estimated weight loss was 16.2% on 5 mg (week 28) and 22% on 20 mg (36 weeks). Patients taking the placebo experienced weight gain at an estimated 1.9%, 2.3%, and 2% for weeks 20, 28, and 36, respectively. Furthermore, the safety profile was consistent with other incretin-based therapies, demonstrating gastrointestinal events being mild to moderate in severity.¹

“We are very encouraged by the subcutaneous phase 1b/2a results for amycretin in people living with overweight or obesity,” Martin Lange, executive vice president for Development at Novo Nordisk, said in a release.¹ “The results seen in the trial support the weight lowering potential of this novel unimolecular GLP-1 and amylin receptor agonist, amycretin, that we have previously seen with the oral formulation.”

The company plans to investigate the drug further for adults with overweight or obesity.¹

READ MORE: Obesity Management Resource Center

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References

1. Novo Nordisk successfully completes phase 1b/2a trial with subcutaneous amycretin in people with overweight or obesity. News release. Novo Nordisk. January 24, 2025. Accessed February 3, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915251

2. Collins L, Costello RA. Glucagon-Like Peptide-1 Receptor Agonists. [Updated 2024 Feb 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551568/

3. Roth JD, Maier H, Chen S, Roland BL. Implications of Amylin Receptor Agonism: Integrated Neurohormonal Mechanisms and Therapeutic Applications. Arch Neurol. 2009;66(3):306–310. doi:10.1001/archneurol.2008.581

4. A Research Study on How NNC0487-0111 Works in People With Overweight or Obesity. ClinicalTrials.gov identification: NCT05369390. Updated July 03, 2024. Accessed February 3, 2025. https://clinicaltrials.gov/study/NCT05369390