The CagriSema clinical trial program includes the REDEFINE and REIMAGINE phase 3 studies. Here is what the results show, plus safety and approval status.
The CagriSema clinical trial program is Novo Nordisk's phase 3 research effort testing a once-weekly combination of cagrilintide and semaglutide for obesity and type 2 diabetes. The flagship study, REDEFINE 1, reported roughly 22.7% average weight loss at 68 weeks in adults who had overweight or obesity without diabetes. CagriSema is still investigational and is not FDA-approved for any indication.
What Is CagriSema?
CagriSema is a fixed-dose combination of two appetite-regulating hormones given as a single weekly injection. Semaglutide is a GLP-1 receptor agonist — the same molecule sold as Ozempic and Wegovy. Cagrilintide is a long-acting amylin analog that works through a separate pathway to slow digestion and reduce hunger.
The investigational dose used in the phase 3 studies is 2.4 mg semaglutide plus 2.4 mg cagrilintide. The reasoning behind the pairing is simple: two complementary hormone signals may produce greater weight loss than either drug alone.
Inside the REDEFINE Phase 3 Trials
Novo Nordisk runs its cagrisema phase 3 work under two umbrellas. REDEFINE covers obesity and overweight, while REIMAGINE covers type 2 diabetes. The main obesity studies look like this:
| Trial | Population | Comparator | Status and headline result |
|---|---|---|---|
| REDEFINE 1 | Overweight or obesity, no diabetes | Placebo | Completed; about 22.7% weight loss at 68 weeks |
| REDEFINE 2 | Obesity plus type 2 diabetes | Placebo | Completed; about 13.7% weight loss at 68 weeks |
| REDEFINE 3 | Obesity with established cardiovascular disease | Placebo | Ongoing; combines heart outcomes with weight endpoints |
| REDEFINE 4 | Obesity | Tirzepatide 15 mg | Head-to-head study; topline data expected 2025–2026 |
The REDEFINE 1 phase 3 readout drew the most attention because expectations were high. Novo Nordisk had suggested the trial might approach 25% weight loss, and the final average came in below that mark.
How CagriSema Compares With Other Weight-Loss Drugs
Cross-trial numbers are the only way to line these therapies up so far, because most of them have never been tested against each other directly.
| Therapy | Mechanism | Reported average weight loss | Regulatory status |
|---|---|---|---|
| Semaglutide 2.4 mg (Wegovy) | GLP-1 | About 15% at 68 weeks | Approved for chronic weight management |
| Tirzepatide 15 mg (Zepbound) | GIP and GLP-1 | About 21% at 72 weeks | Approved for chronic weight management |
| CagriSema 2.4 mg/2.4 mg | Amylin and GLP-1 | About 22.7% at 68 weeks | Investigational |
| Retatrutide | GIP, GLP-1, and glucagon | About 24% at 48 weeks (phase 2) | Investigational |
These figures come from separate studies with different populations, durations, and statistical methods, so they should not be read as a ranking. Direct evidence will come from REDEFINE 4, which compares CagriSema with tirzepatide 15 mg. Anyone weighing a retatrutide vs cagrisema comparison right now is working from indirect data. For context, clinical trials retatrutide have reported average weight loss above 24% at 48 weeks, but those results come from a different population and design.
What the REDEFINE 1 Results Showed
In REDEFINE 1, participants on CagriSema lost an average of 22.7% of their body weight at 68 weeks, compared with 2.3% on placebo. Those numbers reflect the intention-to-treat analysis, which counts every randomized participant, including those who stopped treatment early.
- About 57% of participants were still taking the highest 2.4 mg/2.4 mg dose at the end of the trial.
- Many participants never escalated to the top dose, which company researchers said pulled the average down.
- Gastrointestinal side effects were the leading reason people reduced or stopped treatment.
The companion study, REDEFINE 2, enrolled adults with type 2 diabetes and overweight or obesity. Weight loss there averaged about 13.7% at 68 weeks versus 3.4% on placebo, alongside improvements in blood sugar control.
Peer-reviewed write-ups of the cagrisema results have appeared in the New England Journal of Medicine and The Lancet, giving clinicians a fuller view than the initial company announcements.
REIMAGINE Trials for Type 2 Diabetes
While REDEFINE focuses on weight, the REIMAGINE program tests CagriSema in people with type 2 diabetes. These trials compare the combination with placebo, semaglutide 1.0 mg, and other glucose-lowering treatments.
The goal is to show that CagriSema lowers A1c at least as well as existing options while also producing meaningful weight loss. Novo Nordisk has said it plans to pursue a type 2 diabetes indication alongside its obesity filing.
Phase 1 and Phase 2 Data
The cagrilintide clinical trials that began before CagriSema tested the amylin analog on its own, mostly for weight management and diabetes. Those early studies established the dosing schedule and confirmed that cagrilintide could be paired with semaglutide without unexpected interactions.
A 32-week phase 2 study published in The Lancet in 2023 enrolled adults with type 2 diabetes and overweight or obesity. Participants on CagriSema 2.4 mg/2.4 mg lost about 15.6% of body weight, compared with roughly 5.1% on semaglutide 2.4 mg alone and 8.1% on cagrilintide alone.
Other investigational compounds are moving through much earlier stages, from a mots-c clinical trial exploring metabolic and mitochondrial effects to aod 9604 clinical trials studying a growth hormone fragment for fat metabolism.
Safety, Side Effects, and Approval Status
Gastrointestinal symptoms dominate the CagriSema safety profile, as they do for other GLP-1-based drugs. Nausea, vomiting, diarrhea, and constipation are the most common complaints, and they tend to be worst during dose escalation.
Serious risks described for this drug class include pancreatitis and gallbladder disease. Semaglutide-containing products also carry a boxed warning about thyroid C-cell tumors and are contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN2. Anyone considering treatment should review these risks with a healthcare professional.
CagriSema is not FDA-approved for human use in the United States. Novo Nordisk has said it intends to submit regulatory filings in the first quarter of 2026, so any FDA decision would come later in the year at the earliest. Until approval and launch, the only way to receive CagriSema is through a clinical trial.
Frequently Asked Questions
Is CagriSema approved by the FDA?
No. CagriSema is investigational and has not been approved by the FDA for any use. Novo Nordisk has said it plans to submit regulatory filings in the first quarter of 2026, so an FDA decision would come after that review. Until then, the drug is available only to participants in clinical trials.
What were the CagriSema REDEFINE 1 results?
In REDEFINE 1, adults with overweight or obesity and no diabetes lost an average of about 22.7% of their body weight at 68 weeks on CagriSema, compared with 2.3% on placebo. Roughly 57% of participants were still taking the highest 2.4 mg/2.4 mg dose at the end of the trial. Gastrointestinal side effects were the most common reason for dose reduction or discontinuation.
How does CagriSema compare with tirzepatide (Zepbound)?
In separate trials, CagriSema produced about 22.7% weight loss at 68 weeks and tirzepatide 15 mg produced about 21% at 72 weeks, but those studies were not head-to-head. The REDEFINE 4 trial is the first direct comparison between the two, and its results will give the clearest answer. Cross-trial comparisons alone are not reliable evidence.
This page provides educational research information and does not replace medical advice, diagnosis, or treatment.