Subcutaneous Amycretin Yields Promising Weight Loss in Phase 1b/2a Trial

Topline data from a Phase 1b/2a clinical trial were positive for once-weekly subcutaneous amycretin, a glucagon-like peptide-1 (GLP-1) and amylin receptor agonist intended for the treatment of overweight or obesity.1

Announced by Novo Nordisk on January 24, 2025, amycretin demonstrated a safety profile similar to other incretin-based therapies, with an estimated body weight loss of up to 22% over a total treatment duration of 36 weeks, if patients adhered to treatment.

“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,” Martin Holst Lange, executive vice president for development at Novo Nordisk, said in a statement.1

Amycretin is a unimolecular long-acting GLP-1 and amylin receptor agonist under development for adults with overweight or obesity and for adults with type 2 diabetes (T2D), with both subcutaneous and oral administration. Novo Nordisk previously released Phase 1 data from the oral amycretin program, demonstrating its use was associated with a mean reduction in body weight of –13% at 12 weeks among 16 patients with a mean baseline body weight of 89 kg.2

Across 5 parts, this randomized, placebo-controlled, and double-blinded study evaluated the safety, tolerability, pharmacokinetics, and proof-of-concept of subcutaneous amycretin administration in people with overweight or obesity. A single ascending dose (Part A) was assessed for pharmacokinetics and the starting dose for the first multiple-dose cohort. In the second part, the safety and tolerability of amycretin were determined using dose escalation until 36 weeks of treatment duration (Part B).1

In the proof-of-concept part of the trial, Novo Nordisk evaluated body weight loss for up to 36 weeks by escalating amycretin to levels of 1.25 mg, 5 mg, and 20 mg dosed for 12 weeks, respectively (Part E, D, and C). The primary endpoint of treatment-emergent adverse events (TEAEs) was assessed in 125 people with overweight or obesity.

Analysis showed a consistent safety profile with incretin-based therapies, with the most common adverse events being gastrointestinal and mild-to-moderate severity. Assessment of the treatment effects of amycretin, based on treatment adherence, revealed an estimated weight loss of 9.7% on the 1.25 mg (20 weeks), 16.2% on 5 mg (28 weeks), and 22.0% on 20 mg (36 weeks) doses from a mean baseline body weight of 92.7 kg.

On the other hand, those treated with placebo experienced an estimated 1.9%, 2.3%, and 2.0% body weight gain, respectively. Citing the positive effect of amycretin on weight loss, and its well-tolerated and consistent safety profile, Novo Nordisk announced plans for further clinical development of amycretin for overweight or obesity.

“We are very encouraged by the subcutaneous Phase 1b/2a results for amycretin in people living with overweight or obesity,” Lange added.1

References

1. Novo Nordisk successfully completes phase 1b/2a trial with subcutaneous amycretin in people with overweight or obesity. Novo Nordisk. January 24, 2025. Accessed January 24, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915251.
2. Campbell P. Novo Nordisk delivers updates on development of semaglutide, CAGRISEMA, Amycretin, and more. HCP Live. March 7, 2024. Accessed January 24, 2025. https://www.hcplive.com/view/novo-nordisk-delivers-updates-on-development-of-semaglutide-cagrisema-amycretin-and-more.