Eli Lilly and Novo Nordisk Bet on Amylin to Power Next Wave of Obesity Treatments

Pharmaceutical manufacturers Eli Lilly and Novo Nordisk are looking past standalone GLP-1 therapies toward a pancreatic hormone pathway known as amylin, aiming to build combination and monotherapy regimens that advance weight loss and serve patients who do not respond to existing drugs. As reported by CNBC Business (https://www.cnbc.com/2026/10/02/lilly-novo-amylin-obesity-drugs.html), the clinical push targets millions of individuals who experience inadequate efficacy, tolerability hurdles, or weight-loss plateaus on standard GLP-1 medications alone.

Eli Lilly reported Phase 2 trial results for its experimental amylin agonist, eloralintide, administered alongside tirzepatide, the active compound in its Zepbound and Mounjaro treatments. In a 48-week efficacy analysis of adults with obesity and Type 2 diabetes who stayed on therapy, patients receiving the highest-dose combination lost an average of 23.3% of their body weight, compared to 14.8% for participants taking a high dose of tirzepatide alone. Benjamin Bikman, a professor at Brigham Young University who studies metabolic health, noted that patients with Type 2 diabetes typically see less weight reduction on metabolic therapies than non-diabetic cohorts.

Wall Street analysts view the amylin pipeline as a substantial commercial opportunity. Leerink Partners analyst David Risinger projected $23.2 billion in annual sales for Lilly's eloralintide portfolio by the end of 2035, forecasting a standalone drug launch in 2029 followed by the combination therapy in 2030. Risinger told CNBC that more than 10 million people have tried GLP-1s and discontinued them due to tolerability, lack of efficacy, or genetic non-responsiveness. Ken Custer, president of Lilly Cardiometabolic Health, noted that combination regimens are designed to assist patients who fail to achieve target outcomes from either tirzepatide or eloralintide monotherapy.

Tolerability remains a primary hurdle as Lilly prepares to advance eloralintide into Phase 3 trials later this year. Across dose cohorts in the Phase 2 study, side-effect-related discontinuations for the combination treatment ranged from 10.8% to 27%, compared with 2.9% for tirzepatide monotherapy. Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women's Hospital, warned that a 27% discontinuation rate presents a significant clinical barrier. Bikman stressed that real-world effectiveness will depend on whether late-stage trial protocols can keep patients on the regimen.

Novo Nordisk is also advancing a multi-asset amylin portfolio. The Danish drugmaker plans to introduce CagriSema—a fixed-dose combination of its amylin analog cagrilintide and semaglutide—early next year, with standalone cagrilintide and a higher-dose CagriSema formulation targeted for 2028. Novo is also running Phase 2 trials on amycretin (zenagamtide), a single dual-agonist molecule targeting GLP-1 and amylin in both once-weekly injectable and once-daily oral formulations. Competitors including Pfizer, AstraZeneca, and Viking Therapeutics are also developing amylin candidates.

While an early amylin drug was approved in the United States over two decades ago for mealtime diabetes management alongside insulin, patient adoption was constrained by the need for multiple daily injections. The new generation of amylin analogues uses long-acting formulations requiring only once-weekly administration. Amylin suppresses appetite, increases satiety, and slows gastric emptying through different neuro-metabolic pathways than GLP-1, allowing combination therapies to target multiple biological mechanisms simultaneously without relying entirely on escalating single-agent doses.

Early research suggests multi-pathway targeting may also influence behavioral and organ health markers. Novo Nordisk reported yearlong functional MRI data showing that CagriSema altered brain response to calorie-dense food in regions governing cravings and self-control, reducing intrusive food-related thoughts. Martin Holst Lange, Novo's chief scientific officer, noted the neurological changes were tied to quality-of-life gains. The broader industry shift toward multi-receptor agonists—including Lilly's triple-agonist retatrutide targeting GLP-1, GIP, and glucagon—reflects an effort to develop tailored metabolic therapies as clinical trials progress.