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Drugmakers are testing a new class of therapies that target the pancreas hormone amylin as a way to extend or complement the current wave of GLP-1 obesity medicines. Early clinical data suggest these agents could produce deeper weight loss for some patients or provide options for people who do not get sufficient benefit from existing drugs.
Lilly’s Phase 2: bigger losses, but more side effects
Eli Lilly reported Phase 2 results showing that adding its experimental amylin drug, eloralintide, to tirzepatide produced substantially greater weight reductions than tirzepatide alone in people with obesity and Type 2 diabetes. At 48 weeks, participants on the highest-dose combination lost an average of 23.3% of body weight versus 14.8% for those on a high dose of tirzepatide alone, based on an efficacy analysis that assumes continued treatment throughout the trial.
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The company plans Phase 3 studies later this year, and is developing eloralintide both as a standalone therapy and as a combination product. Leerink Partners analyst David Risinger told CNBC he expects the standalone drug to launch in 2029 and the combination in 2030, forecasting as much as $23.2 billion in annual sales for Lilly’s eloralintide franchise by 2035. Risinger added that “there are millions of individuals, potentially over 10 million people, who have tried GLP-1s and failed” for efficacy or tolerability reasons and could benefit from a new mechanism.
Experts welcomed the efficacy signal but stressed caution. “These are encouraging results,” said Benjamin Bikman, a metabolic-health researcher at Brigham Young University, noting that adults with Type 2 diabetes typically lose less weight on these therapies than people without diabetes. At the same time, tolerability was a concern: discontinuation rates in the combination arms ranged from 10.8% to 27%, versus 2.9% for tirzepatide alone in the study. “A therapy is only effective if patients can remain on it,” Bikman said.
Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, warned that a 27% dropout rate “is not a good number.” Lilly executives say some patients may need the complementary approach—Ken Custer, president of Lilly Cardiometabolic Health, noted that patients might not get what they need from tirzepatide or from eloralintide alone.
How amylin works and why companies are betting on it
Amylin is a hormone secreted by the pancreas alongside insulin that helps regulate hunger and fullness. Like GLP-1, it slows gastric emptying and suppresses appetite, but it does so through a separate biological pathway. That difference is the rationale for combining amylin analogs with GLP-1 drugs: targeting multiple mechanisms could produce larger metabolic effects than doubling down on a single pathway.
The first amylin therapy approved in the U.S. was introduced more than 20 years ago as a mealtime injection for people using insulin, but it saw limited uptake because it required multiple daily shots. New molecules under development are long-acting and designed for weekly dosing, which developers say should improve convenience and adherence.
Other players and combination strategies
Novozymes’s rival programs have already shown the promise of amylin combinations. Novo Nordisk’s amylin analog cagrilintide delivered meaningful weight loss as a single agent, and the combo with semaglutide—marketed as CagriSema—produced even larger reductions in clinical trials. Novo expects CagriSema to launch early next year, with standalone cagrilintide and a higher‑dose combo arriving in 2028.
Novo is also testing a single molecule called amycretin or zenagamtide that targets both GLP-1 and amylin, in weekly injection and daily oral tablet forms. The company reported promising Phase 2 results earlier this year. In a separate yearlong functional MRI study, Novo said CagriSema reduced persistent thoughts about food—so-called “food noise”—and altered brain responses to high-calorie foods in regions tied to cravings, pleasure and self-control. “The signal in the brain changes in a way that actually is associated with improved quality of life,” said Martin Holst Lange, Novo’s chief scientific officer.
Other major drugmakers, including Pfizer, AstraZeneca and Viking Therapeutics, are advancing amylin programs as well. The pursuit of amylin is part of a broader shift toward multi-hormone approaches: tirzepatide already combines GLP-1 and GIP, while Lilly’s experimental retatrutide adds glucagon and has produced some of the largest weight-loss results reported to date. Bikman noted published data for retatrutide show substantial reductions in liver fat, triglycerides and fasting insulin.
Whether amylin-based combinations will ultimately outperform existing next-generation treatments remains to be proven in larger, late-stage trials and regulatory reviews. For now, the developments underscore a growing industry effort to expand therapeutic choices for people with obesity and Type 2 diabetes.
