Eloralintide moves into Phase 3 alone and in combination with tirzepatide

Eli Lilly has moved its experimental amylin drug eloralintide into Phase 3 trials, both as a standalone treatment and in combination with tirzepatide, the active ingredient in Mounjaro and Zepbound.^[2] Two Phase 3 studies, called ENLIGHTEN-1 and ENLIGHTEN-6, began in February 2026 and were still recruiting participants as of September 2026, with primary results not expected before 2028.^[2]

Eloralintide is a selective amylin receptor agonist, a different mechanism from the GLP-1 drugs that currently dominate the market.^[1] Amylin is a hormone released alongside insulin that signals fullness to the brain, slows stomach emptying and may help restore sensitivity to leptin, another hormone involved in appetite control.^[2] In a 48-week Phase 2 trial of 263 adults, eloralintide produced weight loss ranging from 9% at the 1 mg dose up to 20% at the 9 mg dose, compared with 0.4% on placebo.^[2] That 20% figure would put eloralintide's monotherapy results on par with some of the strongest GLP-1 data reported so far.

That effect came with tradeoffs. Nausea rates in the Phase 2 trial ranged from 11% to 64% across dose groups, compared with 14% on placebo, and the highest-dose group saw nausea in 64% of participants.^[2] Fatigue reached as high as 46% in some arms.^[2] By comparison, a competing amylin drug called petrelintide, being developed by Zealand Pharma with Roche, produced smaller weight loss of 10.7% in its own Phase 2 trial but reported vomiting rates of 3% on drug versus 6.2% on placebo, meaning fewer people vomited while on the drug than on placebo.^[2] Petrelintide's Phase 3 program is expected to start in the second half of 2026, and a second Phase 2 trial in people with type 2 diabetes is due to report later this year.^[2]

Other amylin programs are moving on overlapping schedules. Novo Nordisk's cagrilintide, tested alone, produced weight loss of 10.8% at 26 weeks and 11.5% at 68 weeks; combined with semaglutide as CagriSema, it reached 20.4% at 68 weeks versus 14.9% for semaglutide alone.^[2] CagriSema has been filed with the FDA, with a decision expected in late 2026.^[2] But in February 2026, a trial called REDEFINE-4 pitted CagriSema directly against tirzepatide at its highest dose over 84 weeks and did not show CagriSema was as good, with tirzepatide coming out ahead.^[2] That result raises questions about whether pairing amylin drugs with incretins will reliably beat existing tirzepatide-based treatment, though the comparison involved a different amylin drug and partner than Lilly's combination.^[2]

Why it matters for patients

For patients currently on Ozempic, Wegovy, Mounjaro or Zepbound, none of this changes anything about their current treatment. Eloralintide, petrelintide and cagrilintide are not approved for use in the United States and remain in clinical testing.^[1][2] The appeal of amylin drugs is a different side-effect profile: some data suggest these drugs may cause less gastrointestinal upset than GLP-1 drugs, and there is early, unproven interest in whether they preserve muscle better during weight loss, though a leading amylin researcher has said the preclinical evidence on muscle preservation is not yet conclusive.^[2] Patients weighing GLP-1 treatment today should know that a wave of amylin-based options, either alone or combined with tirzepatide or semaglutide, is being tested but will not be available for years.

What happens next

ENLIGHTEN-1 and ENLIGHTEN-6, testing eloralintide alone and with tirzepatide, are expected to report primary results no earlier than 2028.^[2] Petrelintide's second Phase 2 trial, ZUPREME-2, is expected to report later in 2026, with Phase 3 starting in the second half of the year.^[2] A decision from the FDA on Novo Nordisk's CagriSema is expected in late 2026.^[2]