Key TakeawaysIn a phase 1 trial, Novo Nordisk’s experimental obesity drug amycretin led to up to 13% weight loss in just three months.Amycretin targets GLP-1 receptors and a second hormone called amylin.Amylin appears to act in the brain, rather than in the gut. It’s possible that amylin can control appetite with fewer gastrointestinal side effects.

Key Takeaways

In a phase 1 trial, Novo Nordisk’s experimental obesity drug amycretin led to up to 13% weight loss in just three months.Amycretin targets GLP-1 receptors and a second hormone called amylin.Amylin appears to act in the brain, rather than in the gut. It’s possible that amylin can control appetite with fewer gastrointestinal side effects.

An experimental new pill from Novo Nordisk, called amycretin, could cause substantial weight loss in people with obesity.

The once-daily oral medication is in the same class as the blockbuster obesity and diabetes medications, Ozempic and Mounjaro. It targets GLP-1 receptors and stimulates levels of a second hormone called amylin.

In a phase 1 clinical trial, researchers tested if the drug was safe for humans at different doses. Although regulatory approval is still years away, early data suggests that the drug could lead to rapid weight loss. Participants taking amycretin at the highest doses lost up to 13% of their body weight in just three months.

That outcome is “remarkable,” saidDavid Lau, MD, PhD, professor emeritus and director of the Julia McFarlane Diabetes Research Centre at the University of Calgary, who was not involved with the study. “This adds to the current and future investigations and development of weight loss medications to help people to achieve better body weight and, of course, overall health.”

Would You Be More Likely to Take GLP-1s If They Came in Pill Form?

How Amycretin Works

Combining amylin and GLP-1 receptor agonists into one medication could stimulate weight loss in more ways than semaglutide, which targets GLP-1 alone.

“The data are very consistent that amylin agonists actually affect appetite centrally in the brain. But what we don’t know is the exact location in the brain where amylin works,” Lau said. “If amylin acts differently from the GLP-1 receptor agonists, there may be an additive effect on appetite regulation. If they act on different parts of the brain, they may have better effect.”

New Weight Loss Drugs Are on the Way That Could Upstage Wegovy and Ozempic

What We Know From the Clinical Trial

The trial included 144 participants between the ages of 18 and 55 years who had a BMI of 25 to 40 and were otherwise considered healthy.

Novo Nordisk used the same technology to create an oral form of amycretin as it uses for Rybelsus, the oral version of semaglutide.

The researchers tested multiple dosing regimens. In a presentation of the data,Agnes Gasiorek, PhD, senior clinical pharmacology specialist at Novo Nordisk, highlighted a portion of the study in which the dosage for some participants about doubled every two to three weeks for three months.

That outcome “really is remarkable for an orally delivered biologic,” Gasiorek said.

Gasiorek said it’s too early to compare the benefits of amycretin with semaglutide or other obesity medications. Future studies will test how amycretin affects the body over a longer period.

One challenge of developing an oral version is making the drug effective at the lowest dose possible. About 1% of oral semaglutide is bioavailable, so people need to take a much higher dose of the medication to receive the same effect as an injectable dose.Novo Nordisk hasn’t yet studied what percentage of amycretin is absorbed orally.

Hitting a Weight Loss Plateau on Ozempic or Wegovy

Striving for Weight Loss With Fewer GI Side Effects

In the trial data presented last week, Novo Nordisk reported that most people experienced mild to moderate gastrointestinal side effects, such as nausea, vomiting, and abdominal pain. The likelihood of those side effects increased as participants started taking higher doses of amycretin.

Amylin appears to act in the brain, rather than in the gut. Scientists are still learning about which parts of the brain are responsible for nausea and which parts amylin stimulates, but it’s possible that amylin helps control appetite while signaling less gastrointestinal discomfort.

For companies competing to create the most tolerable and effective obesity and diabetes medications, Lau said a primary goal is to understand how to target certain hormones to induce weight loss without nausea.

How Common Is Stomach Paralysis From Obesity Medication?

Where Amycretin Could Fit Into Obesity Care

Novo Nordisk will advance the once-daily oral tablet to phase 2 clinical trials. The company is also testing a subcutaneous injection version of the drug.

Lau said that GLP-1 receptor agonists will continue to be the “major ingredient” for future anti-obesity medications. Drugs that also target another hormone or two have the potential to be more potent.

For instance, Eli Lilly’s tirzepatide stimulates GLP-1 and GIP receptors and causes greater average weight loss in clinical trials than semaglutide, which targets GLP-1 alone. A drug in phase 3 clinical trials, called retatrutide, targets three different hormones with promising effects.

“Obesity, as a condition, is actually very heterogeneous. Some people respond tremendously, other people don’t,” Lau said.

Someone who is a “super responder” to GLP-1 drugs may lose sufficient weight when taking a drug that contains amylin with even fewer side effects than they may experience on semaglutide, for instance.

What This Means For YouIf you’re interested in obesity management options, talk to a health provider about your treatment options. You canuse this toolfrom the Obesity Medicine Association to find an obesity medicine provider.

What This Means For You

If you’re interested in obesity management options, talk to a health provider about your treatment options. You canuse this toolfrom the Obesity Medicine Association to find an obesity medicine provider.

4 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Enebo LB, Berthelsen KK, Kankam M, et al.Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial.Lancet. 2021;397(10286):1736-1748. doi:10.1016/S0140-6736(21)00845-X

Sanyal AJ, Kaplan LM, Frias JP, et al.Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.Nat Med. 2024;30(7):2037-2048. doi:10.1038/s41591-024-03018-2

Meet Our Medical Expert Board

Share Feedback

Was this page helpful?Thanks for your feedback!What is your feedback?OtherHelpfulReport an ErrorSubmit

Was this page helpful?

Thanks for your feedback!

What is your feedback?OtherHelpfulReport an ErrorSubmit

What is your feedback?