Semaglutide plus an amylin analog, in one weekly shot. Novo Nordisk's combination candidate beat semaglutide alone in its first published phase 3 trial — here's what the NEJM data actually says.
CagriSema is a once-weekly injection combining semaglutide — the GLP-1 in Ozempic and Wegovy — with cagrilintide, a long-acting amylin analog. Amylin is a hormone released alongside insulin that slows stomach emptying and signals fullness through a receptor pathway separate from GLP-1. The idea behind stacking the two: hit appetite from two directions at once, rather than pushing one pathway harder.
It isn't approved yet. But it's the furthest along of the next-generation combination candidates, with 68-week phase 3 results now published in a peer-reviewed journal rather than just a company press release.
REDEFINE-1 randomized adults with overweight or obesity (a weight-related condition, no diabetes) to once-weekly CagriSema 2.4mg/2.4mg, semaglutide 2.4mg alone, cagrilintide 2.4mg alone, or placebo, alongside standard lifestyle counseling, for 68 weeks. Results were published in the New England Journal of Medicine in 2025.
Among participants who stayed on treatment for the full 68 weeks, average loss with CagriSema rose to 22.7%, and 40.4% lost at least a quarter of their starting body weight. The combination didn't just match the better of its two components — it beat both, which is the signal trial designers were looking for.
CagriSema also moved the numbers doctors track alongside weight: 88% of participants with prediabetes returned to normal blood glucose, alongside improvements in systolic blood pressure, waist circumference, and lipid levels. GI side effects were more common than with semaglutide alone — nausea in roughly 55% vs. 13% on placebo — but mostly mild-to-moderate and clustered during dose increases, and only about 6% of participants stopped treatment because of them.
Sources: REDEFINE-1 trial, New England Journal of Medicine, 2025 (doi:10.1056/NEJMoa2502081) · presented at the American Diabetes Association 85th Scientific Sessions, see ADA 2025 coverage · Novo Nordisk trial results announcement, PR Newswire.
CagriSema isn't on pharmacy shelves yet — Novo Nordisk has indicated it's preparing regulatory filings off this data, but approval timelines for new combinations typically run a year or more from a single phase 3 readout. Nothing here changes what to do with a current semaglutide or tirzepatide prescription.
What's worth noting is the pattern, not just the drug. Every next-generation candidate in this class — CagriSema, retatrutide, and others in development — keeps the same once-weekly injection cadence. If one of these reaches approval, it slots into the same weekly reminder habit people already use for Ozempic, Wegovy, or Zepbound, not a new routine.
This article summarizes a single published phase 3 trial and associated conference presentation for general education. CagriSema is investigational and not yet approved by the FDA or EMA. This is not medical advice — talk to your prescriber about your own treatment options.