Novo Nordisk's Amycretin Shows Promise in Weight Loss, Challenges Remain

Novo Nordisk's experimental weight loss drug amycretin has demonstrated continued efficacy in a 36-week phase 1b/2a trial, potentially positioning it as a strong competitor to Eli Lilly's Zepbound. However, tolerability concerns and dosing questions persist, highlighting the complex landscape of obesity treatments.

Sustained Weight Loss and Dosing Considerations

The latest data, published in The Lancet, reveals that amycretin's effect on body weight showed no signs of plateauing after 36 weeks of treatment. Patients receiving weekly injections experienced a mean weight loss of 22%, with the trend remaining consistent throughout the study period. This suggests the potential for even greater weight reduction in longer-term trials, possibly surpassing the 25.8% weight loss observed with Zepbound after 88 weeks.

However, the optimal dosing strategy for amycretin remains unclear. The study evaluated maintenance doses of 1.25 mg, 5 mg, and 20 mg, with overlapping response curves observed across these doses. While the 20-mg dose group reported the highest weight loss, this cohort also remained on treatment for a longer duration, complicating direct comparisons.

Tolerability Concerns and Market Competition

Despite promising efficacy data, amycretin's tolerability profile raises questions about its potential market position. Gastrointestinal side effects were reported in 94% of patients in both the 5-mg and 20-mg cohorts, dropping to 63% in the 1.25-mg group. These high rates of adverse events have fueled uncertainty about amycretin's differentiation from existing and pipeline competitors.

William Blair analysts noted, "We believe the high frequency of adverse events could fuel uncertainty over the asset's differentiation against approved (Zepbound) or late-stage investigational (retatrutide and MariTide) compounds."

Novo Nordisk's Strategic Positioning

Amycretin represents a critical opportunity for Novo Nordisk to develop a market-leading obesity treatment. The company's previous candidate, CagriSema, a combination of semaglutide (the active ingredient in Wegovy) and a long-acting amylin analog, achieved efficacy similar to Zepbound in phase 3 trials but fell short of Novo's weight loss targets.

Recent data on CagriSema in patients with and without Type 2 diabetes, published in the New England Journal of Medicine, support its competitiveness against Zepbound. However, William Blair analysts remain skeptical, stating, "In our view, there is no evidence to suggest CagriSema should be prescribed over Zepbound in any subpopulation, based on the available data released to date."

Novo Nordisk is now preparing to initiate phase 3 trials for both injectable and oral formulations of amycretin, with the program expected to commence in the first quarter of 2026. As the obesity treatment landscape continues to evolve, the company faces the challenge of differentiating its offerings in an increasingly competitive market.