The next generation of weight-loss drugs is taking shape in a way that could significantly change how people approach obesity and Type 2 diabetes. For years, medications that mimic GLP-1, a gut hormone, have dominated the conversation about medical weight loss. Now, a new class of amylin-based medications is emerging that may offer meaningful weight-loss benefits with fewer gastrointestinal side effects, positioning them as an appealing option for people who want weight loss support but struggle to tolerate current treatments.

GLP-1-based drugs such as semaglutide have brought medical weight loss into mainstream awareness. These medications support weight management and help regulate blood sugar, but they are not without drawbacks. According to the reporting, roughly 40% of people who start these drugs stop taking them within a year. The most common reasons are gastrointestinal issues like nausea, vomiting, and stomach cramping. As a result, many individuals who might benefit from pharmacologic help either discontinue therapy or are hesitant to start.

At the annual European Association for the Study of Diabetes (EASD) meeting in Milan, researchers presented data on several experimental injectable drugs that act on amylin pathways. These amylin-based weight-loss drugs appear to work in ways that resemble GLP-1 therapies but seem, at least in early studies, to come with a more tolerable side-effect profile. This early research suggests a potentially important shift in how clinicians might tailor obesity treatment to each person’s health needs and tolerance for side effects.

Amylins are peptide hormones that help regulate appetite signals in the brain and influence how quickly the stomach empties. Like GLP-1s and other incretin-based drugs, they help people feel full and reduce interest in food. However, they bind to different receptors on cells, which means their actions can complement those of GLP-1 medications rather than simply replicate them. That complementary mechanism is one reason combinations of amylin analogues and GLP-1 or related agents are generating interest.

One of the most closely watched experimental treatments is CagriSema, developed by Novo, the company behind Wegovy and Ozempic. CagriSema combines semaglutide with cagrilintide, an amylin analogue that mimics a pancreatic hormone involved in satiety. In a study cited at the conference, people who were overweight or had obesity lost 22.4% of their starting body weight after a year of weekly CagriSema injections compared to those taking a placebo. That level of weight loss places the drug among the more potent medical options currently in development.

The research presented did not stop at the scale. Scientists shared functional MRI data indicating that CagriSema altered brain responses to food. That suggests the drug may help reduce intense food fixations or cravings, which are often reported as some of the most difficult parts of long-term weight management. In participants with Type 2 diabetes, CagriSema also reduced harmful fat in the liver and pancreas. Excess fat in these organs is linked to insulin resistance and metabolic complications, so this early signal raises the possibility of benefits that go beyond weight reduction alone.

Novo’s executive vice president and chief scientific officer, Martin Holst Lange, highlighted another potential effect that is still in emerging stages of research. He noted that an earlier-stage study in people with Type 2 diabetes suggested that CagriSema could reduce neuropathic pain, which affects about half of individuals with the condition. If further trials confirm this, the medication might eventually play a role not only in weight loss and blood sugar control but also in alleviating a particularly burdensome complication of diabetes. Lange described these early findings as exciting and emphasized their potential to improve day-to-day life for people managing chronic disease.

Eli Lilly, the company behind Zepbound (tirzepatide), is exploring a similar combination strategy. Its experimental therapy EloraTZP pairs tirzepatide, a powerful incretin-based drug, with the amylin analogue eloralintide. In a study involving people with overweight or obesity and Type 2 diabetes, EloraTZP led to an average loss of 23% of starting body weight after nearly a year. For comparison, those taking tirzepatide alone lost 14.8%. The combination also produced greater reductions in A1C than either tirzepatide or the amylin compound on its own.

Lilly has investigated the amylin component independently, yet the company now plans to focus more on the combination. The rationale is straightforward. If pairing amylin analogues with incretin drugs can significantly enhance both weight loss and glycemic control, that could create a new standard for combination obesity and diabetes therapies, especially for people who may need more intensive interventions to reach their health goals.

Another entrant is Zealand Pharmaceuticals, a Danish biotech firm. In a study recently published in the Lancet, Zealand’s weekly injectable amylin-based compound, petrelintide, was tested in people who were overweight or obese but did not have diabetes. On average, participants receiving petrelintide lost 10% of their body weight, while those on placebo lost 1.7%. While this reduction is more modest than what was observed with some of the combination therapies, the result is still clinically meaningful for many people seeking moderate weight loss.

What sets petrelintide apart in this early research is its tolerability. Even at the highest doses, participants reported side effects at rates similar to those in the placebo group. Dr. Timothy Garvey, a professor in nutrition sciences and senior scientist at the University of Alabama who led the trial, noted that while amylin-based medications can still cause nausea, it appears at less than half the rate typically seen in GLP-1 trials. For people who cannot stay on, or are wary of starting, GLP-1 therapies because of gastrointestinal issues, this difference could matter a great deal.

Garvey also pointed out that not everyone is looking for or medically requires drastic weight loss. Some people may seek a moderate, sustainable reduction that lowers health risks without the intensity or side-effect burden of more powerful agents. This is where amylin-based drugs might carve out a distinctive role. If these medications offer steady weight loss, relatively mild side effects, and ease of prescribing, they could become a first-line therapy for many individuals or a bridge for those who might later transition to or combine with other options.

Looking ahead, the regulatory landscape will shape how quickly these medications become available. Novo has already submitted CagriSema to the U.S. Food and Drug Administration for approval to treat overweight and obesity in people without diabetes, with a decision expected by the end of the year. The other amylin-based products are at earlier stages of testing, which means more data on safety, effectiveness, and long-term outcomes will be needed. Still, the trajectory is clear. Amylin-based drugs are poised to join GLP-1 and other incretin-based therapies in a growing toolkit of weight-loss and metabolic health medications.

I found it striking how the researchers and clinicians involved keep returning to the idea of individualization. As more medications with different mechanisms, side-effect profiles, and degrees of weight-loss efficacy become available, it may be easier for primary care physicians and specialists to tailor treatments to each person’s needs, tolerances, and goals. Rather than a one-size-fits-all model of obesity care, the emerging picture is one of personalized strategies that balance effectiveness with quality of life.

If the results seen so far hold up in larger, longer-term studies, amylin-based drugs could represent an important next step in medical weight management. They do not replace the need for nutrition, movement, and behavioral support, but they might make it more feasible for many people to reach and maintain healthier weights without the same level of discomfort that currently leads many to discontinue therapy. In a field that is moving quickly, this new class of medications underscores how science is continuously expanding the options for treating complex conditions like obesity and Type 2 diabetes in a more precise and humane way.

Read more at https://time.com/article/2026/10/01/next-generation-of-weight-loss-drugs-is-almost-here/