CagriSema is a once-weekly shot that pairs cagrilintide 2.4 mg, a long-acting amylin analog, with semaglutide 2.4 mg, the drug in Wegovy. In the REDEFINE 1 trial, people without diabetes lost an average of 20.4% of their body weight at 68 weeks, compared with 3.0% on placebo. In REDEFINE 2, people with type 2 diabetes lost 13.7%, compared with 3.4%. Below: each published trial, what amylin does in plain words, and where approval stands.
| Trial | Who | Length | Weight change | Comparison |
|---|---|---|---|---|
| Phase 2 (Frias, Lancet 2023) | 92 adults with type 2 diabetes | 32 weeks | -15.6% | Semaglutide -5.1%, cagrilintide -8.1% |
| REDEFINE 1 (NEJM 2025) | 3,417 adults, no diabetes | 68 weeks | -20.4% | Placebo -3.0% |
| REDEFINE 2 (NEJM 2025) | 1,206 adults with type 2 diabetes | 68 weeks | -13.7% | Placebo -3.4% |
| REDEFINE 5 (Lancet Diabetes Endocrinol 2026) | 331 adults in Japan and Taiwan | 68 weeks | -18.4% | Semaglutide 2.4 mg -11.9% |
All weight figures are mean changes from the start of each trial, taken from the abstracts. The REDEFINE 1 and 2 numbers use the treatment-policy estimand, which counts everyone who was randomized, whether or not they kept taking the drug. REDEFINE 5 used the trial product estimand, which estimates the effect if everyone had kept taking it. That difference matters when you compare numbers across trials.
Amylin is a hormone made in the pancreas by the same cells that make insulin. The two are stored together and released together when you eat. The FDA label for pramlintide (Symlin), an older amylin drug, lists what amylin does: it slows how fast food leaves the stomach, it holds back glucagon, a hormone that makes the liver release sugar, and it acts on the brain to reduce appetite (Symlin label, 12.1).
Pramlintide does not last long. The Symlin label gives a half-life of about 48 minutes, and it is injected before major meals (Symlin label, 2 and 12.3). Cagrilintide was built to last much longer. In a phase 1b trial it had a half-life of 159 to 195 hours, about a week, with peak levels 24 to 72 hours after a shot. In the same trial semaglutide 2.4 mg had a half-life of 145 to 165 hours (Enebo, Lancet 2021). Because both last about a week, they can be given together once weekly. You can see what a weekly shot with that half-life looks like in the cagrilintide half-life calculator. For a short definition, see amylin analog in the glossary.
Novo Nordisk describes the pair as targeting "complementary obesity-related pathways" (company statement). In plain terms: two hormones that both affect hunger and fullness, through different receptors, given in one weekly shot.
The first test of the pair in type 2 diabetes was a 32-week phase 2 trial at 17 US sites, published by Frias and colleagues in the Lancet in 2023 (PMID 37364590). It enrolled 92 adults with a BMI of 27 or more who were taking metformin, with or without an SGLT2 inhibitor. They were split into three equal groups: CagriSema, semaglutide alone or cagrilintide alone, all stepped up to 2.4 mg.
| Measure at week 32 | CagriSema | Semaglutide 2.4 mg | Cagrilintide 2.4 mg |
|---|---|---|---|
| HbA1c change | -2.2 points | -1.8 points | -0.9 points |
| Body weight change | -15.6% | -5.1% | -8.1% |
| Time in glucose range (baseline to week 32) | 45.9% to 88.9% | 32.6% to 76.2% | 56.9% to 71.7% |
| Nausea (trial record) | 9 of 31 | 5 of 31 | 4 of 30 |
HbA1c is a measure of average blood sugar over about three months. CagriSema lowered it more than cagrilintide alone. The difference from semaglutide alone, -0.4 points, did not reach statistical significance. Weight was a different story: CagriSema beat both single drugs on weight loss. Time in range is the share of the day blood sugar stayed between 3.9 and 10.0 mmol/L on a glucose monitor.
Side effects were mostly mild or moderate and gut-related. Adverse events of any kind were reported by 68% on CagriSema, 71% on semaglutide and 80% on cagrilintide. No level 2 or level 3 low blood sugar was reported (the two more serious grades), and there were no deaths. The nausea counts in the table come from the ClinicalTrials.gov results page (NCT04982575). With 92 people, this was an early signal.
REDEFINE 1 is the main phase 3 trial, published in the New England Journal of Medicine in 2025 by Garvey and colleagues (PMID 40544433). It enrolled adults without diabetes who had a BMI of 30 or more, or 27 or more with at least one weight-related condition. Everyone also got lifestyle support.
| Measure | CagriSema | Placebo | Source |
|---|---|---|---|
| Weight change, treatment-policy | -20.4% | -3.0% | NEJM paper |
| Weight change, trial product estimand | -22.7% | -2.3% | Novo Nordisk (company) |
| Lost 5% or more | 91.9% | 31.5% | Novo Nordisk (company) |
| Any gut side effect | 79.6% | 39.9% | NEJM paper |
| Nausea | 55% | 12.6% | Novo Nordisk (company) |
| Constipation | 30.7% | 11.6% | Novo Nordisk (company) |
| Vomiting | 26.1% | 4.1% | Novo Nordisk (company) |
| Stopped for side effects | 5.9% | 3.5% | Novo Nordisk (company) |
| Systolic blood pressure change | -10.9 mm Hg | -2.8 mm Hg | Hypertension 2026 |
The paper also says people on CagriSema were more likely than those on placebo to reach 20%, 25% and 30% weight loss. Most gut side effects were short-lived and mild to moderate. A blood pressure analysis found that 39.6% of people on CagriSema who used blood pressure medicine cut back or stopped it during the trial, against 18.8% on placebo (Verma, Hypertension 2026).
How did the single drugs do? The abstract we could open does not give the weight change in the semaglutide-alone and cagrilintide-alone groups, so we do not quote it here. One later analysis does compare all four groups on a different measure. It counted people who reached both a BMI under 27 and a waist-to-height ratio under 0.53 at week 68. The shares were 30.3% on CagriSema, 19.1% on semaglutide, 9.0% on cagrilintide and 3.3% on placebo (Busetto, Diabetes Obes Metab 2026).
A note on dosing: we could not open the full REDEFINE 1 paper. So we do not report how many people stayed on the top dose or how dose changes were handled during the trial.
REDEFINE 2 ran in 12 countries and was published alongside REDEFINE 1 by Davies and colleagues (PMID 40544432). It enrolled 1,206 adults with type 2 diabetes, a BMI of 27 or more and an HbA1c of 7% to 10%. People were assigned 3:1, giving 904 on CagriSema and 302 on placebo, for 68 weeks with lifestyle support.
Weight loss was smaller than in REDEFINE 1. The two trials enrolled different people, so that gap is a difference between trials, not a head-to-head result.
REDEFINE 1 had a small semaglutide-alone group, but REDEFINE 5 was built as a straight comparison of CagriSema against semaglutide 2.4 mg alone (Yamauchi, Lancet Diabetes Endocrinol 2026). It ran at 22 sites in Japan and Taiwan and enrolled 331 adults, about a quarter of whom had type 2 diabetes. After 68 weeks, weight fell 18.4% on CagriSema and 11.9% on semaglutide, a difference of 6.5 percentage points. Gut side effects were close: 53% vs 51%. Ten percent stopped CagriSema and 6% stopped semaglutide.
It used Japanese obesity criteria, so the numbers may not carry over directly to other groups.
Not as of October 22, 2026, as far as we can find. Novo Nordisk announced on December 18, 2025 that it had submitted a New Drug Application to the FDA for CagriSema 2.4 mg/2.4 mg for weight management, based on REDEFINE 1 and 2. In that release, Novo said CagriSema "is not approved in the US or EU" and that the FDA was expected to review the application in 2026 (company statement). A search of the FDA's Drugs@FDA database through openFDA on October 22, 2026 returned no matches for cagrilintide (openFDA).
CagriSema adds a second hormone to semaglutide instead of changing the GLP-1 drug itself. That is a different approach from retatrutide, a single molecule acting on three receptors (see retatrutide phase 2 results explained), and from orforglipron (see orforglipron trial results).
If you take more than one compound, keeping a clean record helps. Dose Track logs each dose for every compound you take, keeps count of what is left in each vial, sends reminders, and lets you log side effects next to the shot that came before them. The cagrilintide compound guide covers vial and syringe-unit math. For semaglutide alone, see the Wegovy page.
This article is general information, not medical advice. CagriSema is not FDA approved. Talk to your prescriber before you start, change or stop any medicine.