Is amycretin the next big GLP-1?

Just when you thought you’d heard of all the different hunger hormones that hold sway over your appetite — GLP-1, GIP, glucagon — along comes amylin. Although not yet approved by the FDA, this naturally occurring peptide is the star of an investigational medication known as amycretin. Like the GLP-1 medications that came before it, amycretin works by helping you feel fuller and eat less. 

While it's still several years away from FDA approval or potentially reaching pharmacy shelves, early research suggests amycretin — which is now officially called zenagamtide by the World Health Organization — could produce some of the largest weight-loss results seen to date. Here's what we know about how amycretin works, how much weight people have lost in studies so far, and how it compares with today's GLP-1 medications.

Key takeaways

• Amycretin (now called zenagamtide) is an investigational oral and injectable medication that activates both GLP-1 and amylin receptors in a single molecule.

• In an early-stage clinical trial of adults with overweight or obesity, participants lost up to 24.3% of their body weight after 36 weeks on amycretin.

• Amycretin has entered phase 3 clinical trials, but it will likely be several years before it could become available (and that hinges on it receiving FDA approval).

Amycretin (zenagamtide) is an investigational medication developed by Novo Nordisk, the company behind Ozempic and Wegovy. It's part of a new generation of weight-loss drugs designed to target more than one hormone involved in appetite and metabolism. Similar to tirzepatide, which targets GLP-1 and GIP, amycretin acts on two different hormone pathways. “Zenagamtide is a single molecule peptide that activates both GLP-1 receptors and amylin receptors,” says Dr. Peminda K. Cabandugama, M.D., an endocrinologist at the Cleveland Clinic and spokesperson for The Obesity Society. “It's the first medication of its class with this mechanism of action.” The idea is that being a dual-agonist makes zenagamtide more effective at reducing appetite, regulating blood sugar, and increasing feelings of fullness.

To understand why researchers are excited about amycretin (zenagamtide), it helps to know a little about the two hormones it targets and about how GLP-1s work in general. GLP-1 helps people feel fuller by targeting appetite receptors in the brain and slowing gastric emptying. It also stimulates insulin release when blood sugar rises after eating. Those effects reduce hunger, decrease calorie intake, and improve blood sugar control. Amylin does that too, but through a different biological pathway.

"Amylin is a natural hormone secreted alongside insulin by the pancreas in response to food intake,” says Dr. Vanita Aroda, M.D., director of diabetes clinical research at Brigham and Women's Hospital, who has been involved in amycretin research. “Like GLP-1, it enhances satiety through receptors in the brain, delays stomach emptying, and regulates post-meal blood sugars."

Amycretin targets both amylin receptors and GLP-1 receptors simultaneously, which researchers hope may produce greater effects than stimulating either one alone. While there is some overlap in how GLP-1 and amylin work, Aroda says, their distinct pathways may complement one another, potentially leading to larger benefits for weight loss, blood sugar control, and overall cardiometabolic health.

The idea of combining hormones in a single treatment isn’t unique to amycretin — that’s also the idea behind several other next-generation obesity medications. That's because body weight is controlled by a complex network of hormones rather than a single hunger on/off switch. “The human body is beautifully interconnected and uses an intricate circuit of feedback mechanisms to protect its weight ‘ set points, ’ which is why losing weight and keeping it off can be a challenge,” says Aroda. “While there are dozens of hormones involved in hunger and satiety, the ones emerging in drug development today are unique because they have been manipulated to support weight loss. Each new therapy unveils a little more of our underlying biology and physiology, and having options available allows us to individualize care.”

Although amycretin (zenagamtide) is still in clinical trials, the early results have been significant. In a 2025 phase 1b/2a study published in The Lancet, adults with overweight or obesity who received the highest once-weekly dose of injectable amycretin lost an average 24.3% of their body weight after 36 weeks — and there were no signs of a plateau at that point, meaning they could conceivably continue to lose more weight if they stayed on the medication. 

More recently, Novo Nordisk presented results from a separate phase 2 study involving adults with type 2 diabetes. Those taking the highest dose of amycretin saw significant improvements in their blood sugar control and lost up to 14.6% of their body weight after 36 weeks.

“These results demonstrate a high magnitude of weight loss,” says Aroda, though she cautions that these were phase 2 studies and therefore designed primarily to identify the dose that should move forward into larger phase 3 clinical trials. By the time the drug is reviewed by the FDA, the approved dosing regimen may differ, meaning the final weight-loss numbers could change.

Both an oral and injectable form of amycretin are currently in development. And early results on the pill form are promising: An exploratory study found that participants who took a daily pill containing 100 mg of amycretin lost an average 13.1% of their body weight over 12 weeks. Based on the findings, both the pill and the injection have advanced to phase 3 clinical trials that are underway now.

Amycretin is part of a growing pipeline of obesity medications. Here's how it compares with other existing and emerging options.

Amycretin vs. semaglutide (Ozempic/Wegovy)

The biggest difference between amycretin and semaglutide is the number of hormone pathways each medication targets. Semaglutide, the active ingredient in Ozempic and Wegovy, works by activating just the GLP-1 hormone receptors. That helps regulate appetite, slow stomach emptying, and improve blood sugar control. The investigational drug amycretin activates both GLP-1 and amylin hormone receptors to amplify feelings of fullness and potentially produce greater weight loss than a GLP-1 receptor agonist alone. 

There hasn’t been a head-to-head trial comparing the effectiveness of amycretin and semaglutide in people with overweight or obesity. But so far, in an early trial of injectable amycretin, participants lost a maximum average 24.3% of their body weight, while a phase 3 trial of injectable Wegovy HD found a max average 18.8% of weight loss.

A look at amycretin, CagriSema, retatrutide, and orforglipron

Amycretin isn’t the only anti-obesity medication in development right now. Here’s a look at some of the other investigational drugs at varying stages of development (and one — Foundayo — that was recently approved).

*Effectiveness numbers are based on the maximum average percentage of body weight lost in a latest-stage clinical trial in adults with obesity or overweight. Note that these studies differed in their design, participants, duration, and dosing, and final dosages may change between phase 1/2 and phase 3 clinical trials and before FDA approval. Without a head-to-head clinical trial, it’s not possible to say whether one medication is truly more effective than another.

So far, there’s not much difference between the potential downsides of amycretin compared to other drugs in its class. “Just like all other GLP-1 receptor agonists in the market, the side effects are mild to moderate and gastrointestinal in nature," says Cabandugama. In early clinical trials, the most common side effects included nausea, vomiting, diarrhea, and constipation. As with other GLP-1 meds, higher doses tended to cause gastrointestinal symptoms more often than lower doses. Future clinical trials will better clarify amycretin’s side effects in the final dosages that move forward toward potential approval.

Amycretin (zenagamtide) is not currently FDA-approved, nor is it available for doctors to prescribe. Based on the exploratory research results, the manufacturer has advanced both oral and injectable forms of amycretin to phase 3 clinical trials for both obesity and type 2 diabetes treatment. That means that amycretin is likely still several years away from potentially being available to patients. 

While amycretin is still in development, there are plenty of effective weight-loss medications available now — and Weight Watchers not only provides access to these for qualified members but also supports you as you create the healthy habits you need to be successful in the long-term.

Amycretin (now known as zenagamtide) is a drug currently in development for treating obesity and type 2 diabetes. It activates both GLP-1 and amylin receptors in a single molecule. Early studies have shown impressive weight loss, including up to 24.3% in people with overweight or obesity, but more trials need to be done to determine correct dosing that balances effectiveness with tolerability. If it’s eventually approved, amycretin won't necessarily replace existing medications, but instead will provide another option in the growing range of obesity treatments.