With tirzepatide and semaglutide now mature, FDA-approved products, both Eli Lilly and Novo Nordisk are pouring resources into a different hormone pathway, amylin, that they're betting will define the next generation of obesity treatment. A CNBC report this week pulled together recent trial data and analyst projections that illustrate both the opportunity and the open questions around that bet.

The Data Driving the Optimism

Lilly's Phase 2b trial combining its amylin analog eloralintide with tirzepatide, a combination sometimes called EloraTZP and covered in more detail elsewhere on this site, found up to 23.3% average weight loss at 48 weeks, compared with 14.8% for tirzepatide alone in the same study. The combination also produced a larger A1C reduction, up to 2.9 percentage points versus 2.4 for tirzepatide alone. Novo Nordisk's own amylin-pathway candidate, the cagrilintide-semaglutide combination CagriSema, has reported weight loss of roughly 15.7% over 68 weeks in its own trial program, with the company targeting approval around early 2027.

A Tolerability Debate Resurfaces

The same Lilly trial that produced the 23.3% weight-loss figure also showed a wide range of discontinuation due to side effects, from 10.8% up to 27% depending on dose, compared with 2.9% for tirzepatide alone. Dr. Caroline Apovian, an obesity medicine specialist at Brigham and Women's Hospital, was quoted calling the high end of that range "not a good number." Lilly executives have suggested the dropout was concentrated during the dose-escalation period and that a more gradual titration schedule in Phase 3 trials could reduce it, but that's a hypothesis to be tested, not a demonstrated fix. Ken Custer, who leads Lilly's cardiometabolic health business, framed the strategic logic this way: "Neither tirzepatide nor eloralintide alone may deliver what every patient needs."

What's Behind the Investment

Analysts at Leerink Partners have projected eloralintide-based products could generate roughly $23.2 billion in annual sales by 2035, with Lilly planning a standalone eloralintide launch around 2029 and the tirzepatide combination around 2030. Part of the strategic rationale analysts cite is the large pool of patients who start GLP-1 therapy and later stop, estimated by some analysts at more than 10 million people, often due to side effects, cost, or insufficient results on existing drugs. Both companies frame amylin-pathway drugs as a way to offer those patients, and new patients, a mechanistically different option rather than simply a stronger dose of the same pathway.

Regulatory Status

Neither eloralintide nor amycretin, Novo's other amylin-pathway candidate, is FDA-approved; both remain in clinical trials. CagriSema is further along in development but likewise unapproved as of this writing, with Novo targeting an early 2027 approval window. None of the weight-loss or tolerability figures described here reflect an approved drug's official label, since labels are set by the FDA based on the complete, finalized trial record, not a conference readout or news report.

The Bottom Line

The amylin pathway has real, trial-backed promise for weight loss beyond what current GLP-1 drugs achieve, but the same data driving the excitement also shows a meaningfully higher rate of people stopping treatment due to side effects than with tirzepatide alone. Whether Phase 3 trials and refined dosing schedules close that gap is an open empirical question that won't be settled by investor sales projections.