Novo Nordisk is advancing its amylin agonist, amycretin, to Phase III in type 2 diabetes (T2D) after the drug met its key efficacy endpoints in a Phase II trial.
During the mid-stage, dose finding study (NCT06542874), the subcutaneous (SC) amylin agonist led to significant impacts on HbA1c levels, with up to 89.1% of patients reaching values below 7% on a once-weekly regimen after 36 weeks of treatment. In the once-weekly treatment group, there was a mean reduction in HbA1c of 1.8%.
In those treated with once-daily amycretin, there was a mean HbA1c reduction of 1.5% after 36 weeks, with 77.6% of patients achieving an HbA1c level of below 7%.
Amycretin also exhibited statistically significant weight loss of up to 14.5% over a 36-week period, as compared with the 2.6% rate seen in the placebo group. At the 36-week mark, there was no weight loss plateau observed.
Meanwhile, the drug’s safety and tolerability profile remained consistent with other incretin and amylin-based therapies.
These results succeed the positive outcome of Novo Nordisk’s Phase II trial of amycretin in obesity, which prompted the company to take the drug to late-stage trials after it triggered weight loss of up to 22% across a 36-week dosing period.
Shehroz Mahmood, senior analyst at GlobalData, noted that amycretin’s weight loss data from the T2D study was encouraging. “The absence of a weight loss plateau suggests potential for further improvement with extended treatment, which could challenge current efficacy benchmarks set by Lilly’s Zepbound (tirzepatide),” he said.
GlobalData is the parent company of Clinical Trials Arena.
Now, Novo Nordisk will also take amycretin to Phase III in T2D, with the trial set to begin in 2026.
While this is a positive step forward for Novo Nordisk, Mahmood noted that the timeline disadvantage on Eli Lilly is significant. “With Phase III starting in 2026, market entry likely won't occur until 2028-2029, giving Lilly's portfolio several years of market establishment,” he commented.
The obesity/T2D fight continues
This Phase II win comes at a tough time for Novo Nordisk, which is currently facing fierce competition from its most prominent weight loss rival, Eli Lilly, in both T2D and obesity.
It all began with Lilly’s cataclysmic rise within the metabolic health segment, after its assets Mounjaro and Zepbound (tirzepatide) helped accelerate the company to become the first pharma to reach the $1bn market cap club – joining the likes of tech giants Apple and Microsoft.
Meanwhile, Novo Nordisk has suffered from this rivalry, as evidenced by its gradually declining stock value. Since 26 November 2024, the company’s share price has fallen by nearly 60% – dropping from the Dkr745 ($115) mark to Dkr304 ($47) at opening on the same day in 2025.
The company’s stock value isn’t the only thing experiencing a downturn, as Novo Nordisk’s CEO, Mike Doustdar, once again trimmed the company’s 2025 outlook on 5 November, citing slowing growth in glucagon-like peptide 1 receptor agonist (GLP-1RA) sales as the primary reason.
The company is also contending with a board member exodus, as well as its recent loss in a M&A bidding war for Metsera with Pfizer.
However, Mahmood notes that amycretin could have the potential to turn the company’s fortunes around.
“Amycretin has the potential to become the next frontier in the obesity space if it delivers quality weight loss rather than simply the highest percentage reduction, along with superior tolerability rates compared to established players,” he stated.
“Quality weight loss encompasses metabolic improvements beyond absolute weight reduction, preservation of lean body mass, and sustained long-term maintenance – factors that collectively determine whether a therapy delivers meaningful clinical benefit to patients.”
While the amycretin approach is being investigated as a combination therapy approach by several companies, Mahmood noted that Novo Nordisk’s “unique unimolecular formulation” could lead to its market success.
