Pharmaceutical companies are pursuing a new strategy in obesity treatment by developing drugs that target the amylin pathway, a biological mechanism distinct from GLP-1-based therapies. Rather than replacing existing medications like Lilly’s tirzepatide and Novo’s semaglutide, these amylin-based treatments are designed to work alongside or enhance current options for patients seeking additional weight loss or alternatives to GLP-1s.
Eli Lilly presented Phase 2 trial data this week showing that its experimental amylin drug eloralintide, when combined with tirzepatide, produced substantially greater weight loss than tirzepatide alone. Patients receiving the highest-dose combination lost an average of 23.3% of body weight at 48 weeks, compared with 14.8% for those taking only tirzepatide. The company is developing eloralintide both as a standalone treatment and in combination therapy, with analysts forecasting significant commercial potential. Lilly plans to begin Phase 3 trials later this year, though tolerability remains a concern, as discontinuation rates due to side effects ranged from 10.8% to 27% depending on dosage levels in the Phase 2 study.
Novo Nordisk has pursued a comparable strategy with cagrilintide, its amylin-based therapy. The company’s combination product CagriSema, pairing cagrilintide with semaglutide, is expected to launch early next year, with additional standalone and higher-dose versions following in 2028. Novo is also developing amycretin, a single molecule targeting both GLP-1 and amylin pathways, currently in Phase 2 testing as both a weekly injection and daily oral form. Other major pharmaceutical companies, including Pfizer, AstraZeneca, and Viking Therapeutics, are similarly developing amylin products.
Amylin is a hormone released in the pancreas that regulates hunger and fullness through mechanisms distinct from GLP-1, offering a complementary biological approach. Experts note that targeting multiple biological pathways simultaneously could produce greater metabolic benefits than single-pathway approaches. Novo’s recent data indicated that CagriSema reduced food-related rumination and showed improvements in organ and bone health markers in a functional imaging study. Industry analysts estimate that amylin-based therapies could address millions of patients who have not achieved adequate results from existing GLP-1 medications.
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