In short: CagriSema is an investigational once-weekly injection that combines cagrilintide, a long-acting amylin receptor agonist, with semaglutide, the ingredient in Wegovy. It is not FDA approved: as of October 6, 2026, there is no FDA approval record or label for it. Novo Nordisk filed for approval in December 2025 and says it expects a decision in the fourth quarter of 2026. In its main trial, average weight change was -20.4% vs -3.0% with placebo over 68 weeks; in a head-to-head trial it lost to tirzepatide (Zepbound).
This explainer covers what CagriSema is, what each trial found, what the side effects looked like, and what an FDA decision would and would not change. For the approved medicines you can use today, see every FDA-approved weight-loss medication compared and our medications hub; for the wider pipeline, see emerging weight-loss medications.
What CagriSema is
Novo Nordisk describes CagriSema as a fixed-dose combination of a long-acting amylin receptor agonist (cagrilintide) and a GLP-1 receptor agonist (semaglutide), injected under the skin once a week. In the main trials, both parts were built up to 2.4 mg each. Semaglutide 2.4 mg on its own is already approved as Wegovy; our GLP-1 guide explains how that half works. Because cagrilintide acts on amylin receptors and semaglutide on GLP-1 receptors, the combination works through two different hormone pathways at once.
Novo is studying it in two programs: REDEFINE for adults with overweight or obesity, and REIMAGINE for adults with type 2 diabetes. A large cardiovascular outcomes trial, REDEFINE 3, is listed with about 7,000 participants, and the company says a higher-dose trial started in 2026.
CagriSema in numbers
- 3,417adults randomized in REDEFINE 1, the main weight trialGarvey WT et al., NEJM 2025
- 68 weekslength of REDEFINE 1 and REDEFINE 2
- Dec 2025New Drug Application filed with the FDA (company-reported)Novo Nordisk, Sept 30, 2026
- Q4 2026when Novo says it expects the FDA decision
Checked on October 6, 2026
What the placebo-controlled trials showed
REDEFINE 1 (published in the New England Journal of Medicine in 2025) enrolled 3,417 adults without diabetes who had a BMI of 30 or more, or 27 or more with a weight-related condition. Participants were assigned to CagriSema (2,108 people), semaglutide alone (302), cagrilintide alone (302) or placebo (705), all with lifestyle support, for 68 weeks. Counting everyone as randomized, whether or not they kept taking the drug, average weight change was -20.4% with CagriSema and -3.0% with placebo, a difference of 17.3 percentage points.
REDEFINE 2 enrolled 1,206 adults with type 2 diabetes and a BMI of 27 or more. Average weight change at 68 weeks was -13.7% with CagriSema vs -3.4% with placebo. By the end, 73.5% of people on CagriSema had an HbA1c (a three-month blood sugar measure) of 6.5% or less, compared with 15.9% on placebo. People with type 2 diabetes usually lose less weight on these medicines than people without it, which is also true for approved GLP-1 medicines.
| Item | CagriSema | Placebo |
|---|---|---|
| REDEFINE 1 (no diabetes) | 20.4% | 3% |
| REDEFINE 2 (type 2 diabetes) | 13.7% | 3.4% |
Treatment-policy estimand (everyone randomized, whether or not they kept taking the drug). Bars show percent weight lost.
Source: Garvey WT et al. and Davies MJ et al., NEJM 2025 (REDEFINE 1 and 2) (checked on October 6, 2026)
You may also see higher numbers, such as the 22.4% Novo cited in September 2026. Companies often report an “if everyone took it as intended” estimate alongside the stricter one. Both are real, but they answer different questions, so check which one a headline uses. On this site we lead with the stricter treatment-policy number when it is published.
Reading CagriSema headlines: a quick guide
- Which estimand? “Treatment policy” or “treatment regimen” counts everyone who was randomized; “trial product” or “efficacy” assumes everyone took the drug as planned and gives a bigger number.
- Compared with what? A result against placebo is not a result against Wegovy or Zepbound. Only REDEFINE 4 and 5 compared CagriSema with an approved medicine directly.
- Who was studied? People with type 2 diabetes, or in East Asian trials, often show different average results.
- Published or announced? A peer-reviewed paper gives full methods and data; a company announcement or conference talk is a first report. We label which is which.
- Approved or expected? “Expected decision” is the company’s timing. Only an FDA action makes a medicine approved.
Head-to-head trials: against semaglutide and tirzepatide
REDEFINE 5 (Lancet Diabetes and Endocrinology, 2026) compared CagriSema with semaglutide 2.4 mg alone in 331 adults in Japan and Taiwan, about a quarter of whom had type 2 diabetes. Assuming the drugs were taken as intended, weight change at 68 weeks was -18.4% with CagriSema vs -11.9% with semaglutide. That suggests the cagrilintide half adds weight loss on top of semaglutide, at least in that population.
REDEFINE 4 was an open-label, 84-week trial in 809 adults with obesity and at least one related condition, comparing CagriSema 2.4/2.4 mg with tirzepatide 15 mg, the top dose of Zepbound. Novo announced in February 2026 that the main goal, showing CagriSema was not worse than tirzepatide, was not met. Average weight change was -20.2% with CagriSema vs -23.6% with tirzepatide counting everyone, or -23.0% vs -25.5% if everyone had stayed on treatment. In people with type 2 diabetes (REIMAGINE 4, 68 weeks), Novo reported in August 2026 that CagriSema was non-inferior to tirzepatide 15 mg on weight (-15.2% vs -15.8% if all adhered) but not on HbA1c.
| Item | CagriSema | Comparator |
|---|---|---|
| REDEFINE 5 vs semaglutide 2.4 mg (68 wk) | 18.4% | 11.9% |
| REDEFINE 4 vs tirzepatide 15 mg (84 wk) | 20.2% | 23.6% |
Different estimands: REDEFINE 5 assumes the drug was taken as intended; REDEFINE 4 bars count everyone randomized. Different trials and populations.
Source: Yamauchi T et al., Lancet Diabetes Endocrinol 2026 (REDEFINE 5); Novo Nordisk company announcement, Feb 23, 2026 (REDEFINE 4, company-reported) (checked on October 6, 2026)
For context on the two molecules it was measured against, see semaglutide vs tirzepatide. REDEFINE 4 results were company-reported at the time we checked; we found no peer-reviewed paper yet.
Side effects in the trials
As with approved GLP-1 medicines, digestive side effects were the most common. In REDEFINE 1, 79.6% of people on CagriSema reported a gastrointestinal adverse event (nausea, vomiting, diarrhea, constipation or abdominal pain) vs 39.9% on placebo; in REDEFINE 2 the figures were 72.5% vs 34.4%. The authors described them as mainly transient and mild to moderate. Novo described CagriSema as well tolerated in REDEFINE 4. There is no FDA label yet, so there is no official list of warnings, boxed warnings or interactions. The approved semaglutide labels give a sense of what regulators look at; our GLP-1 side effects guide covers those.
| Item | CagriSema | Placebo |
|---|---|---|
| REDEFINE 1 | 79.6% | 39.9% |
| REDEFINE 2 | 72.5% | 34.4% |
Mostly transient and mild to moderate, per the trial authors.
Source: Garvey WT et al. and Davies MJ et al., NEJM 2025 (checked on October 6, 2026)
Newer data from September 2026
At the European Association for the Study of Diabetes meeting on September 30, 2026, Novo presented a 52-week brain-imaging (fMRI) study showing changes in brain responses to high-calorie food cues, which it linked to fewer cravings (“food noise”), plus REIMAGINE 1 (189 adults with type 2 diabetes, 40 weeks) and REIMAGINE 2 (2,713 adults, 68 weeks) results on body fat, organ fat and bone. These were company-reported conference findings; we will add details once full papers are published.
CagriSema timeline so far
| When | What happened | Source type |
|---|---|---|
| 2025 | REDEFINE 1 and REDEFINE 2 results published in the New England Journal of Medicine | Peer-reviewed trials |
| December 2025 | Novo Nordisk files a New Drug Application with the FDA for weight management, based on REDEFINE 1 and 2 | Company-reported |
| 2026 | REDEFINE 5 (vs semaglutide, Japan and Taiwan) published in Lancet Diabetes and Endocrinology | Peer-reviewed trial |
| February 23, 2026 | REDEFINE 4 headline results: main goal against tirzepatide not met | Company-reported |
| August 2026 | REIMAGINE 4 (type 2 diabetes, vs tirzepatide) reported in Novo’s half-year report | Company filing (SEC Form 6-K) |
| September 30, 2026 | New data at the EASD meeting; decision still expected in Q4 2026 | Company-reported |
| Q4 2026 (expected) | FDA decision | Company expectation, not an FDA date |
Who took part in the trials
Knowing who was studied helps you judge how the results might apply. REDEFINE 1 included adults without diabetes with a BMI of 30 or higher, or 27 or higher with at least one obesity-related condition. REDEFINE 2 was run in 12 countries in adults with type 2 diabetes, a BMI of 27 or more and an HbA1c between 7% and 10%, assigned three to one to CagriSema or placebo. REDEFINE 5 used Japanese obesity criteria: a BMI of at least 27 with two or more obesity-related conditions, or at least 35 with one; 68% of its participants were men. REDEFINE 4 enrolled 809 adults with obesity and at least one related condition, with an average starting weight of 114.2 kg (about 252 lb). Everyone in these trials also received lifestyle support, which is why the placebo groups lost some weight too.
What we still do not know
- Heart outcomes. REDEFINE 3, a cardiovascular outcomes trial of about 7,000 people, is still running. Semaglutide alone has shown a heart-risk benefit (the basis of Wegovy’s cardiovascular indication), but that cannot be assumed for the combination.
- Longer-term safety. The main trials lasted 68 to 84 weeks. An FDA label would summarize the safety data the agency reviewed, including any warnings.
- What happens after stopping. With approved GLP-1 medicines, much of the weight tends to return after stopping; CagriSema results on this have not been published.
- Body composition. Novo has presented data on body fat and organ fat, but full papers were not out when we checked.
- Price and coverage. Nothing official exists until a medicine is approved and launched.
What the FDA decision means
An FDA review checks whether the trial evidence shows a medicine is effective for a specific use and that its benefits outweigh its risks for the people on the label. If the FDA approves CagriSema, it would publish a label stating exactly who it is for (likely based on REDEFINE 1 and 2, the trials Novo says the filing used), the dose steps, warnings and side-effect rates. The FDA could also ask for more information, which would delay a decision. Until a decision is announced, any launch date or price you see is speculation.
If CagriSema is approved: what to check
- The labelWho it is for, the dose steps, the boxed warning if any.
- CoverageInsurers decide separately whether and how to cover a new drug.
- PriceThe maker sets list and self-pay prices; we will add them with a date.
- Your situationWhether it makes sense compared with approved options is a decision for you and your clinician.
Approval would not change three things: the medicine would still need a prescription, coverage for weight medicines would still vary widely (see our insurance guide), and like other weight medicines it would be meant for long-term use alongside eating and activity changes. Strength training and enough protein help protect muscle on any of these medicines, as our muscle loss guide explains.
How it compares with what is approved today
It is tempting to line CagriSema up against approved medicines, but only REDEFINE 4 and REDEFINE 5 were true head-to-head trials. For reference, in their own placebo-controlled trials Wegovy (STEP 1) averaged -14.9% at 68 weeks and Zepbound 15 mg (SURMOUNT-1) -20.9% at 72 weeks, with different people and designs. Another investigational medicine, retatrutide, has also reported Phase 3 results and is expected to be filed in 2027. Our Wegovy vs Zepbound page explains how to read trial numbers like these.
Can you get CagriSema now?
Only by taking part in a clinical trial. ClinicalTrials.gov lists Novo’s CagriSema studies, and a trial team can tell you whether you are eligible. Anything sold online as CagriSema or cagrilintide outside a trial is not an approved medicine. The FDA has warned that compounded or “research use” versions of unapproved ingredients can contain the wrong amount, the wrong substance or contaminants; our compounded GLP-1 guide explains the risks. We will update this page within a week of any FDA action, and the monthly weight-loss news roundup tracks the decision date.
