CagriSema is Novo Nordisk’s investigational once-weekly injection that pairs two appetite-regulating peptides: cagrilintide 2.4 mg, a long-acting amylin analogue, and semaglutide 2.4 mg, the GLP-1 drug in Wegovy and Ozempic. In phase 3 trials it produced about 20% average weight loss over 68 weeks in adults without diabetes, and roughly a third of the weight lost in a body-composition substudy was lean tissue.
The single most important fact: CagriSema is not approved anywhere as of November 7, 2026. Novo Nordisk filed a New Drug Application with the FDA in December 2025. In its nine-month report of November 4, 2026, the company said it is “preparing for the US launch of CagriSema in early 2027, subject to regulatory approval” (Novo Nordisk 9M 2026 report). A head-to-head trial against tirzepatide did not meet its main goal.
This page summarizes what the published trials, company filings and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Fixed-dose combination of an amylin analogue (cagrilintide) and a GLP-1 receptor agonist (semaglutide) |
| Developer | Novo Nordisk |
| Route | Subcutaneous injection once weekly |
| Doses studied | 2.4 mg/2.4 mg in the main phase 3 trials; 1.0 mg/1.0 mg in later phase 3 trials (REDEFINE 9, REIMAGINE 5); 2.4 mg/7.2 mg planned in a high-dose trial |
| Half-life | Cagrilintide 159–195 h; semaglutide 145–165 h (phase 1b trial) |
| US status | Investigational; NDA submitted December 18, 2025; no FDA decision announced as of November 7, 2026 |
| Other regions | Not approved in the EU; NDA submitted in China, review expected to finish in the first half of 2028 |
| WADA status | Not named on the 2026 List; unapproved, so it falls under S0 (non-approved substances); semaglutide is on the 2026 Monitoring Program |
What it is
CagriSema is not a new molecule. It is two existing investigational and approved peptides given together in one weekly injection:
- Cagrilintide is a lipidated analogue of amylin, a hormone the pancreas releases with insulin after meals. It activates amylin receptors and the calcitonin receptor and acts on appetite centers in the brainstem. It is still investigational on its own. See the cagrilintide page for its structure and single-agent trials.
- Semaglutide is an approved GLP-1 receptor agonist. It slows stomach emptying, raises insulin when blood sugar is high and reduces appetite. See semaglutide.
The idea is that amylin and GLP-1 signals reduce food intake through partly different pathways, so the combination should cause more weight loss than either drug alone. The 2.4 mg semaglutide dose in CagriSema is the same as the Wegovy maintenance dose. Novo Nordisk’s REDEFINE program tests CagriSema for weight management, and its REIMAGINE program tests it for type 2 diabetes.
How it compares with related drugs
| Drug | Mechanism | Status (November 2026) | Library page |
|---|---|---|---|
| Semaglutide | GLP-1 agonist | Approved | Semaglutide |
| Cagrilintide | Amylin and calcitonin receptor agonist | Investigational | Cagrilintide |
| CagriSema | Amylin analogue plus GLP-1 agonist | Under FDA review | This page |
| Tirzepatide | GIP and GLP-1 agonist | Approved | Tirzepatide |
| Amycretin | Single molecule acting on GLP-1 and amylin receptors | Investigational | Amycretin |
| Pramlintide | Short-acting amylin analogue | Approved (diabetes) | Pramlintide |
Pharmacokinetics
The key pharmacokinetic data come from a 20-week phase 1b trial in 95 otherwise healthy adults with overweight or obesity. Participants received semaglutide 2.4 mg plus one of six cagrilintide doses (0.16–4.5 mg) or placebo, with both drugs raised every four weeks (Enebo et al., Lancet 2021).
| Component | Half-life | Median time to peak |
|---|---|---|
| Cagrilintide (0.16–4.5 mg) | 159–195 h | 24–72 h |
| Semaglutide 2.4 mg | 145–165 h | 12–24 h |
Both components last about a week, which fits once-weekly dosing. Cagrilintide exposure rose in proportion to its dose, and adding cagrilintide did not change semaglutide’s exposure or elimination. In this short trial, mean weight loss at week 20 was 17.1% with cagrilintide 2.4 mg plus semaglutide, compared with 9.8% with semaglutide plus placebo.
Regulatory status
Status checked on November 7, 2026:
- United States. Novo Nordisk submitted the NDA on December 18, 2025, for weekly CagriSema 2.4 mg/2.4 mg with diet and exercise for long-term weight management in adults with obesity, or overweight with at least one weight-related condition. The filing was based on REDEFINE 1 and REDEFINE 2. The company said then that “CagriSema is not approved in the US or EU” (Novo Nordisk, December 2025). In February 2026 it said an FDA decision was anticipated by late 2026 (Novo Nordisk REDEFINE 4 release). No approval had been announced by November 7, 2026, and the company is planning a launch in early 2027 if it is approved.
- China. Novo submitted an NDA for CagriSema 2.4 mg/2.4 mg to China’s Center for Drug Evaluation for overweight and obesity, and expects the review to finish in the first half of 2028 (Novo Nordisk 9M 2026 report).
- Type 2 diabetes. The FDA filing covers weight management only. A cardiovascular outcomes trial (REDEFINE 3) is still to report.
- Compounding. FDA states that cagrilintide “cannot be used in compounding under federal law” and has not been found safe and effective for any condition (FDA, content current as of October 1, 2026). Any “CagriSema” mixed from separate vials or sold online is therefore not the product under FDA review.
What the research shows
Obesity without diabetes (REDEFINE 1)
REDEFINE 1 was a 68-week, double-blind phase 3a trial in 3,417 adults with a BMI of 30 or more, or 27 or more with an obesity-related condition, and no diabetes. Participants were randomized 21:3:3:7 to CagriSema, semaglutide 2.4 mg, cagrilintide 2.4 mg or placebo, all with lifestyle support (Garvey et al., NEJM 2025).
| Outcome at 68 weeks | CagriSema | Placebo |
|---|---|---|
| Weight change, treatment-policy estimand (counts everyone randomized) | −20.4% | −3.0% |
| Weight change, trial-product estimand (assumes everyone stayed on treatment) | −22.7% | −2.3% |
| Lost at least 5% of body weight | 91.9% | 31.5% |
| Systolic blood pressure change | −10.9 mm Hg | −2.8 mm Hg |
The difference from placebo was −17.3 percentage points (95% CI −18.1 to −16.6). Responder and trial-product figures are from Novo Nordisk’s filing announcement (Novo Nordisk, December 2025); blood pressure is from a secondary analysis (Verma et al., Hypertension 2026). About 30% of CagriSema users reached both a BMI under 27 and a waist-to-height ratio under 0.53, compared with 19.1% on semaglutide, 9.0% on cagrilintide and 3.3% on placebo (Busetto et al., Diabetes Obes Metab 2026).
Obesity with type 2 diabetes (REDEFINE 2) and the diabetes trials
| Trial | Design | Main result |
|---|---|---|
| Phase 2 (Frias et al., Lancet 2023) | 92 adults with type 2 diabetes; CagriSema vs semaglutide vs cagrilintide, 32 weeks | HbA1c −2.2, −1.8 and −0.9 points; weight −15.6%, −5.1% and −8.1% |
| REDEFINE 2 (Davies et al., NEJM 2025) | 1,206 adults with obesity and type 2 diabetes; CagriSema vs placebo, 68 weeks | Weight −13.7% vs −3.4%; HbA1c 6.5% or lower in 73.5% vs 15.9% |
| REIMAGINE 2 (Buse et al., Lancet Diabetes Endocrinol 2026) | 2,713 adults with type 2 diabetes; six arms including semaglutide 2.4 mg, 68 weeks | HbA1c −1.91 vs −1.75 points with semaglutide 2.4 mg (difference −0.16) |
| REIMAGINE 5 (Novo Nordisk 9M 2026 report) | CagriSema 1.0 mg/1.0 mg vs tirzepatide 5 mg in type 2 diabetes, 60 weeks | Weight −12.4% vs −9.1%; HbA1c reduction non-inferior (company-reported) |
People with type 2 diabetes lose less weight on every GLP-1-based drug, and CagriSema follows that pattern. In diabetes, the extra glucose-lowering it adds on top of semaglutide 2.4 mg was small.
Head-to-head trials
- Against semaglutide (REDEFINE 5). In 331 adults in Japan and Taiwan, CagriSema gave −18.4% vs −11.9% with semaglutide 2.4 mg at 68 weeks (difference −6.5 points) (Yamauchi et al., Lancet Diabetes Endocrinol 2026). A 2026 meta-analysis of five trials (4,746 participants) estimated 6.9 percentage points more weight loss with CagriSema than with semaglutide 2.4 mg alone (Rasool et al., Front Endocrinol 2026).
- Against tirzepatide (REDEFINE 4). This 84-week open-label trial randomized 809 adults with obesity to CagriSema 2.4 mg/2.4 mg or tirzepatide 15 mg. Weight loss was 23.0% vs 25.5% assuming adherence, and 20.2% vs 23.6% regardless of adherence. CagriSema failed to show non-inferiority (that it was not meaningfully worse) to tirzepatide (Novo Nordisk, February 2026).
Lower and higher doses
REDEFINE 9 tested lower doses in people with overweight or obesity; Novo reported 21% weight loss at week 68 with CagriSema 1.0 mg/1.0 mg (Novo Nordisk 9M 2026 report). That result has not been peer reviewed. In the other direction, Novo has planned a phase 3 trial of CagriSema 2.4 mg/7.2 mg (a tripled semaglutide dose), and an 80-week trial called REDEFINE 11 in 600 adults is expected to report in the first half of 2027 (Novo Nordisk, February 2026).
Body composition: fat versus lean mass
This is the question most relevant to people who care about muscle. CagriSema is not an anabolic drug. Like every large calorie deficit, it causes loss of both fat and lean tissue. A dual-energy X-ray absorptiometry (DXA) substudy of REDEFINE 1 measured how the weight lost was split. It included 252 participants and was presented at ObesityWeek 2025 and the European Congress on Obesity in May 2026 (Healio, November 2025; Pharmaceutical Technology, May 2026):
| Arm (DXA subgroup) | Weight change at 68 weeks | Share of weight lost as fat | Share lost as lean soft tissue |
|---|---|---|---|
| CagriSema | −23.9% | 66.9% | 33.1% |
| Semaglutide 2.4 mg | −16.6% | 69.7% | 30.3% |
| Cagrilintide 2.4 mg | −15.0% | 62.9% | 37.1% |
| Placebo | −2.8% | Not reported | 43.3% |
How to read this:
- Lean mass still falls in absolute terms. About one-third of the weight lost was lean soft tissue, which includes muscle, organs and water, not only skeletal muscle. Bone mineral was excluded.
- Body composition still improved. In people who lost at least 30% of their weight, fat fell from 46.3% to 33.2% of body weight and lean soft tissue rose from 51.3% to 63.2% of body weight.
- No sign of extra muscle sparing over semaglutide. The lean share was similar to semaglutide alone. It is also in line with reviews of incretin drugs in general: one meta-analysis put the lean share at 33.3% for incretin drugs, vs 7.7% for diet plus exercise (Busk-Cirera et al., Diabetes Obes Metab 2026), and a review of 40 DXA reports found a mean of 29.1% (Dubin et al., Obesity 2026).
- Strength. Sit-to-stand tests improved similarly with CagriSema and placebo, and the presenter said there was no loss of muscle strength. Effect sizes were not reported in the coverage we could access.
These results come from conference presentations and trade-press reports, not a peer-reviewed paper, and the substudy was small relative to the trial.
Use alongside testosterone or anabolic steroids
No trial has tested CagriSema together with testosterone replacement therapy (TRT) or anabolic-androgenic steroids. A 2026 narrative review found no randomized trials of any GLP-1 drug combined with TRT for body composition, and concluded that the evidence does not support routine combined use (Canal de Velasco et al., Cureus 2026). The only controlled human data are tiny pilot studies, such as one of 10 hypogonadal men on tirzepatide, half of whom also received testosterone undecanoate (Seminara et al., Minerva Endocrinol 2026). None of this tells us how CagriSema behaves in people using supraphysiologic androgen doses, whose heart, blood-pressure and lipid risks differ from those of trial participants.
Side effects and risks
Gastrointestinal effects
Stomach and gut side effects are the main problem. In REDEFINE 1 they affected 79.6% of people on CagriSema vs 39.9% on placebo, mostly mild to moderate and temporary (Garvey et al., NEJM 2025). Novo’s filing announcement gave the breakdown (Novo Nordisk, December 2025):
| Event (REDEFINE 1) | CagriSema | Placebo |
|---|---|---|
| Nausea | 55% | 12.6% |
| Constipation | 30.7% | 11.6% |
| Vomiting | 26.1% | 4.1% |
| Stopped treatment for adverse events | 5.9% | 3.5% |
In REDEFINE 2 (type 2 diabetes), 8.4% stopped for adverse events vs 3% on placebo. Compared with semaglutide alone, the meta-analysis found about three times as many injection-site reactions (RR 3.14) but no significant increase in gastrointestinal events under its main model (Rasool et al., 2026).
Risks carried over from semaglutide
CagriSema contains a full 2.4 mg dose of semaglutide. The Wegovy label carries a boxed warning for thyroid C-cell tumors seen in rodents, plus warnings for pancreatitis, gallbladder disease, low blood sugar, kidney injury from dehydration, severe gastrointestinal reactions, diabetic eye complications, heart rate increase and aspiration during anesthesia (Wegovy label, DailyMed). A final CagriSema label would be expected to include these, but none has been issued.
Gaps in the safety data
- Cardiovascular outcomes. REDEFINE 3 has randomized 7,076 adults with established cardiovascular disease to CagriSema or placebo; results are pending (Cavender et al., Am Heart J 2026).
- Long-term use. The longest completed trial lasted 84 weeks.
- Untested groups. There are no data in lean athletes, in people using AAS, or in pregnancy.
Unregulated products
Products sold as “CagriSema,” “cagri-sema blend” or separate “research” vials of cagrilintide and semaglutide are not FDA-reviewed. FDA says cagrilintide cannot legally be compounded (FDA, 2026). The identity, purity, dose and sterility of such products are unknown.
Legal status and use in sport
CagriSema is a prescription-only investigational drug. It is not named on the WADA Prohibited List, and GLP-1 drugs as a class are not prohibited. However, S0 bans any pharmacological substance with “no current approval by any governmental regulatory health authority for human therapeutic use,” including “drugs under pre-clinical or clinical development” (WADA 2026 Prohibited List). Cagrilintide is unapproved, so CagriSema falls under S0 and is prohibited at all times until a regulator approves it.
Two further points matter for tested athletes:
- Semaglutide is monitored. Markers of semaglutide and tirzepatide are on WADA’s 2026 Monitoring Program, in and out of competition (WADA 2026 Monitoring Program). Monitoring is not a ban, but it means labs are looking for it.
- Cagrilintide can be detected. Anti-doping researchers have mapped cagrilintide’s breakdown products and validated a mass-spectrometry detection method (Alhalabi et al., J Pharm Biomed Anal 2026).
Key takeaways
- A two-drug weekly injection. CagriSema combines the amylin analogue cagrilintide 2.4 mg with semaglutide 2.4 mg; both last about a week in the body.
- Not yet approved. The FDA application was filed in December 2025; as of November 7, 2026 no decision has been announced, and Novo is preparing for a possible US launch in early 2027.
- About 20% weight loss in phase 3. REDEFINE 1 reported −20.4% vs −3.0% on placebo at 68 weeks; it beat semaglutide alone by about 6–7 points but did not prove non-inferior to tirzepatide 15 mg.
- Lean tissue is still lost. In a 252-person DXA substudy, about 33% of weight lost was lean soft tissue, similar to semaglutide alone; it does not build muscle.
- Nausea is common. More than half of participants had nausea in REDEFINE 1, and about 6% stopped for side effects.
- Banned in tested sport for now. As an unapproved product it falls under WADA S0, semaglutide is on the Monitoring Program, and a cagrilintide detection method exists.
Sources
- Novo Nordisk. Financial report for the period 1 January 2026 to 30 September 2026. November 4, 2026. GlobeNewswire.
- Novo Nordisk. Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management. Press release, December 18, 2025. Novo Nordisk.
- Novo Nordisk. REDEFINE 4 head-to-head trial results. Company announcement, February 23, 2026. Novo Nordisk.
- Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397(10286):1736–1748. PubMed.
- Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2025;393(7):635–647. PubMed.
- Davies MJ, Bajaj HS, Broholm C, et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med. 2025;393(7):648–659. PubMed.
- Frias JP, Deenadayalan S, Erichsen L, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023;402(10403):720–730. PubMed.
- Buse JB, Bajaj HS, Dalskov SM, et al. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study. Lancet Diabetes Endocrinol. 2026;14(8):662–677. PubMed.
- Yamauchi T, Becker NP, Hagemann CA, et al. Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2026;14(6):450–462. PubMed.
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- Busetto L, Contreras CO, Christensen MH, et al. Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1. Diabetes Obes Metab. 2026;28(10):9317–9325. PubMed.
- Rasool ZK, Shah R, Batool AEZ, et al. CagriSema versus Semaglutide 2.4 mg monotherapy for weight management in adults with overweight or obesity, with or without type 2 diabetes: a systematic review, meta-analysis, and trial sequential analysis. Front Endocrinol (Lausanne). 2026;17:1903335. PubMed.
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