Beyond Ozempic: Lilly and Novo Chase the Next Obesity Blockbuster With Amylin

The obesity drug gold rush that made Ozempic and Wegovy household names is entering a new phase, and the hormone at the center of it isn’t GLP-1. It’s amylin — a lesser-known pancreatic hormone that drugmakers now believe could unlock billions of dollars in additional weight-loss treatment, either on its own or stacked on top of the blockbuster shots millions of patients already take.

Eli Lilly and Novo Nordisk, the two companies that built empires on tirzepatide and semaglutide, are both pushing deeper into amylin science, betting that the next wave of obesity treatment won’t replace GLP-1 drugs so much as extend their reach. Amylin is released from the pancreas alongside insulin and plays its own role in regulating hunger and satiety, giving researchers a second biological lever to pull — one that can be used independently or layered on top of existing therapies to push weight loss further.

Lilly offered the clearest evidence yet of that strategy this week, releasing Phase 2 data on its experimental amylin-targeting drug eloralintide. In a trial involving patients with obesity and Type 2 diabetes, combining eloralintide with tirzepatide — the active ingredient in Lilly’s Zepbound and Mounjaro — produced dramatically better results than tirzepatide alone. After 48 weeks, patients on the highest-dose combination lost an average of 23.3% of their body weight, compared with 14.8% for those on a high dose of tirzepatide by itself.

Those numbers matter because Type 2 diabetes patients typically see smaller weight-loss results on these therapies than people without diabetes, making the gap all the more notable to researchers watching the space. Benjamin Bikman, a Brigham Young University professor who studies metabolic health, called the results “encouraging,” while noting the real test will come in how patients fare over longer stretches of treatment.

For Lilly, eloralintide is being developed on two tracks: as a standalone drug and as a combination therapy with tirzepatide. Wall Street is already penciling in big numbers for both. Leerink Partners analyst David Risinger projects the eloralintide franchise could generate $23.2 billion in annual sales by the end of 2035, with the standalone version reaching the market first in 2029 and the combination following roughly a year later.

The appeal isn’t just about squeezing more weight loss out of existing patients. Risinger estimates that more than 10 million people have already tried GLP-1 drugs and failed to benefit — whether because the drugs didn’t work well enough, side effects were too severe, or genetic factors made them non-responders. That’s a sizable, underserved population that amylin-based treatments could target as a monotherapy, independent of tirzepatide or semaglutide altogether.

Lilly executives see the opportunity running in both directions. Ken Custer, president of Lilly Cardiometabolic Health, framed it as filling gaps on either side of the treatment spectrum: patients who don’t get enough from tirzepatide alone, and those who don’t get enough from an amylin drug alone. Combining the two, the thinking goes, could capture patients who would otherwise fall through the cracks of either mechanism. Bikman pointed to another use case — patients who start strong on tirzepatide but hit a weight-loss plateau and need an added push.

Still, the excitement comes with real caveats. The results are drawn from a relatively small Phase 2 study, and Lilly must now replicate them in larger Phase 3 trials set to begin later this year. Tolerability is shaping up as the bigger hurdle than efficacy: in the combination arms of the trial, between 10.8% and 27% of patients discontinued treatment due to side effects, depending on dosage, compared with just 2.9% of those taking tirzepatide alone. As Bikman put it, a therapy only works if patients can actually stay on it — meaning tolerability data from the next phase of trials may matter just as much as the weight-loss numbers themselves.

Novo Nordisk, Lilly’s chief rival in the obesity-drug race, is pursuing its own amylin programs as well, underscoring that this isn’t a one-company bet but potentially the next major battleground in a market already worth tens of billions of dollars. If the science holds up through late-stage trials, amylin could do for obesity treatment what combination therapies have done in other chronic disease categories: turning a single blockbuster drug class into a multi-front portfolio business, with options tailored to patients GLP-1s never fully reached.

For now, the promise is real but unproven at scale. Investors, doctors, and patients alike will be watching Phase 3 results closely to see whether amylin’s early numbers hold — and whether people can actually stay on the drugs long enough to realize them.