Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-25. ← Back to Evidence Library

CagriSema: what the evidence says

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

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What is it?

CagriSema is a fixed combination, meaning both drugs come premixed in set amounts in one injection, injected under the skin. ^{R1, R5} It pairs two hormone-like peptides that act in different ways:

• Cagrilintide acts like amylin, a pancreas hormone that helps you feel full. It is experimental and not approved on its own anywhere we have checked. ^R11
• Semaglutide acts like GLP-1, a gut hormone that lowers blood sugar and appetite. It is FDA-approved on its own (Ozempic, Wegovy, Rybelsus).

The idea is that the two together lower appetite and blood sugar more than either alone. In an early trial, adding cagrilintide did not change how much semaglutide was in the blood. ^R5

Does it help weight loss?

All results below are from trials funded by Novo Nordisk. "Treatment-policy" results count everyone, whether or not they kept taking the drug, which gives a more realistic picture.

• Human Obesity without diabetes (REDEFINE 1, phase 3): in 3,417 adults, average weight change was −20.4% on CagriSema vs −3.0% on placebo (treatment-policy). ^R1 Blood pressure also fell more (systolic −10.9 vs −2.8 mm Hg). ^R4
• Human Obesity with type 2 diabetes (REDEFINE 2, phase 3): in 1,206 adults, weight change was −13.7% vs −3.4% on placebo. People with diabetes usually lose less weight on these drugs. ^R2
• Human Versus semaglutide alone (REDEFINE 5, phase 3, Japan and Taiwan): in 331 adults, weight change was −18.4% vs −11.9% on semaglutide alone. This compared the combination with one of its own ingredients, and the main result assumed everyone kept taking treatment. ^R3
• Caution Versus tirzepatide (REDEFINE 4, phase 3, press release only, not yet peer-reviewed): in 809 adults with obesity, CagriSema lost less weight than tirzepatide (−20.2% vs −23.6%, counting everyone) and did not meet the trial's main goal of showing it was not worse. The trial was open-label (everyone knew which drug they got). ^R9
• Unknown How CagriSema's own results in REDEFINE 1 compare with the cagrilintide-only and semaglutide-only groups in that trial: those groups' results are not in the published summary. ^R1

Does it help type 2 diabetes?

• Human Early diabetes on diet and exercise only (REIMAGINE 1): in 189 adults, HbA1c (average blood sugar) fell 1.8 points on the higher-strength arm vs 0.1 on placebo, and weight fell 13.8% vs 1.4%. ^R6
• Human Versus semaglutide or cagrilintide alone (REIMAGINE 2): in 2,713 adults on metformin, HbA1c fell slightly more than on semaglutide alone (1.91 vs 1.75 points). This was statistically significant, but the difference is small. ^R7
• Human Added to basal insulin (long-acting background insulin; REIMAGINE 3): in 274 adults, HbA1c fell 2.33 and 2.10 points on the two CagriSema arms vs 0.66 on placebo, with 10% to 12% weight loss and no severe low blood sugar reported. ^R8
• Human In an earlier phase 2 trial (92 people), the combination did not lower HbA1c significantly more than semaglutide alone, though weight loss was greater. ^R12

Is it safe?

What the trials reported:

• Caution Stomach side effects (nausea, vomiting, diarrhea, constipation, belly pain) were much more common than on placebo: 79.6% vs 39.9% in REDEFINE 1, and 72.5% vs 34.4% in REDEFINE 2. Most were mild to moderate and got better over time. ^{R1, R2}
• Caution Any side effect was a little more common than on semaglutide alone in REIMAGINE 2 (86.9% vs 81.2%). ^R7
• Caution Stopping early: in REDEFINE 5, 10% stopped CagriSema vs 6% on semaglutide alone. ^R3
• Human Low blood sugar: no severe low blood sugar was reported when added to basal insulin, but people taking insulin or sulfonylureas (older blood-sugar-lowering pills such as glipizide or glimepiride) should know that GLP-1 drugs can raise this risk (see the semaglutide page). ^R8
• Unknown Heart safety: the large heart-outcomes trial has not reported results. ^R14
• Unknown Long-term safety and rare harms are unknown.

Combination risks: two drugs, two sets of unknowns

• Caution Semaglutide's warnings come along. The semaglutide label carries a boxed warning (the FDA's strongest label warning) about thyroid C-cell tumors in rodents, and warns about pancreatitis, gallbladder disease, kidney injury from dehydration and low blood sugar. CagriSema contains semaglutide, so these are reasonable to expect; see the semaglutide page. Unknown Whether adding cagrilintide changes any of these risks has not been shown in the published abstracts.
• Caution More stomach effects than either drug alone are possible, because both drugs slow digestion and reduce appetite. Stomach side effects were the most common problem in every trial. ^{R1, R2, R7}
• Caution Don't stack with other GLP-1 drugs. Gray-market blends or adding a separate semaglutide, tirzepatide or retatrutide vial means taking two drugs that act on the same receptor, which no trial on this page tested. Unknown
• Caution Home-mixed "blends" are not CagriSema. Trial CagriSema is a single manufactured product in set amounts. A gray-market blend, or two vials mixed by the user, can have any ratio or strength, and either ingredient can be wrong, contaminated or missing. FDA has warned a seller of a "cagrilintide and semaglutide" product labeled "for research use only." ^R13
• Caution Measuring mistakes. FDA's reports of people hospitalized after drawing up too much from vials meant for many injections involved compounded semaglutide. The same syringe-marking problem applies to blends. See the section on measuring mistakes on our semaglutide page.

What we don't know

• Unknown What is actually in a given gray-market blend (identity, ratio, strength, sterility)
• Unknown Whether CagriSema lowers heart attacks and strokes (REDEFINE 3 results pending) ^R14
• Unknown Long-term safety, and whether weight comes back after stopping
• Unknown Whether FDA will approve it, and on what terms

Is it legal?

Not FDA-approved. Novo Nordisk says it submitted a New Drug Application to FDA on Dec 18, 2025, for weight management, and expects a decision in late 2026. ^R10 [UNVERIFIED: not confirmed on an FDA page; third-party sites report a Dec 18, 2026 goal date, also UNVERIFIED.] Cagrilintide cannot be used in compounding under federal law (FDA, page current as of Oct 1, 2026), so compounded CagriSema is not legal either. ^R11 Novo Nordisk said in December 2025 that CagriSema is not approved in the US or EU [UNVERIFIED: not checked against EMA]. Japan, China and other countries: UNVERIFIED not checked against PMDA or NMPA. WADA: not named on the 2026 Prohibited List; S0 bans unapproved substances not covered elsewhere, and cagrilintide has no approval anywhere we checked, so S0 may apply to CagriSema. WADA has not ruled on it by name ^R15. As of Oct 24, 2026.

What's in the vial?

Real CagriSema is only available inside clinical trials. Anything sold as "CagriSema," "Cagri-Sema" or a cagrilintide-semaglutide blend is unapproved. ^{R11, R13} We have not found published lab tests of gray-market blends. For semaglutide alone, a small study found illegal online vials overfilled, low in purity and contaminated with bacterial toxins; see the semaglutide page. Under the Open Peptide Standard, a GLP-1 vial overfilled by more than 20% is a critical fail (draft threshold). See results at /tests/. A passing test covers one batch, tested on one date. It does not mean the compound itself is safe.

What do users report?

Self-report, not evidence.

Unknown TBD. We'll only list this once we can cite a public source.

Study details

These are doses researchers used, not recommendations. All trials funded by Novo Nordisk. "CagriSema 2.4/2.4" = cagrilintide 2.4 mg + semaglutide 2.4 mg in one injection.

R1–R4, R9 Human: Weight trials (REDEFINE)

Study	People	Route	Dose used	Follow-up	Reported	Side effects / dropouts	Citation
REDEFINE 1 (Garvey 2025), obesity, no diabetes, NCT05567796	2,108 (vs 705 placebo)	Subcutaneous	CagriSema 2.4/2.4 once weekly + lifestyle	68 wk	Weight −20.4% vs −3.0% placebo (treatment-policy)	GI events 79.6% vs 39.9%	PMID 40544433
REDEFINE 1, semaglutide-alone arm	302	Subcutaneous	Semaglutide 2.4 mg once weekly	68 wk	Unknown not in abstract	Not in abstract	PMID 40544433
REDEFINE 1, cagrilintide-alone arm	302	Subcutaneous	Cagrilintide 2.4 mg once weekly	68 wk	Unknown not in abstract	Not in abstract	PMID 40544433
REDEFINE 1 blood pressure (Verma 2026), secondary/post hoc	2,108 vs 705	Subcutaneous	CagriSema 2.4/2.4 once weekly	68 wk	Systolic −10.9 vs −2.8 mm Hg; diastolic −5.4 vs −1.7	Not reported	PMID 41328546
REDEFINE 2 (Davies 2025), obesity + T2D, NCT05394519	904 (vs 302 placebo)	Subcutaneous	CagriSema 2.4/2.4 once weekly + lifestyle	68 wk	Weight −13.7% vs −3.4%; HbA1c ≤6.5%: 73.5% vs 15.9%	GI events 72.5% vs 34.4%	PMID 40544432
REDEFINE 5 (Yamauchi 2026), Japan/Taiwan, NCT05813925	164 (vs 167 semaglutide)	Subcutaneous	CagriSema escalated to 2.4/2.4 once weekly	68 wk	Weight −18.4% vs −11.9% semaglutide 2.4 mg (trial-product estimand, assuming everyone kept taking treatment)	Stopped 10% vs 6%; GI 53% vs 51%; 1 death on semaglutide, judged unrelated	PMID 42009015
REDEFINE 4 (press release), obesity, NCT06131437	809 total, open-label	Subcutaneous	CagriSema 2.4/2.4 once weekly vs tirzepatide 15 mg weekly	84 wk	Weight −20.2% vs −23.6% (treatment-regimen, counting everyone); −23.0% vs −25.5% (efficacy estimand, if everyone stayed on treatment); non-inferiority (proving it is not worse) not met	Mostly mild/moderate GI (company-reported)	R9, not peer-reviewed

R5, R12 Human: Earlier trials

Study	People	Route	Dose used	Follow-up	Reported	Side effects / dropouts	Citation
Phase 1b (Enebo 2021), NCT03600480	12	Subcutaneous	Cagrilintide 2.4 mg + semaglutide 2.4 mg weekly (separate injections)	20 wk + 5 wk follow-up	Weight −17.1% vs −9.8% semaglutide + placebo; cagrilintide did not change semaglutide exposure	Adverse events in 97% (all cagrilintide arms) vs 96%; mostly mild/moderate	PMID 33894838
Phase 2 T2D (Frias 2023), NCT04982575	31	Subcutaneous	CagriSema escalated to 2.4/2.4 once weekly	32 wk	HbA1c −2.2 vs −1.8 semaglutide (p=0.075, not significant); weight −15.6% vs −5.1%	Adverse events 68%; no level 2–3 hypoglycaemia (clinically significant or severe low blood sugar); no deaths	PMID 37364590

R6–R8 Human: Type 2 diabetes trials (REIMAGINE)

Study	People	Route	Dose used	Follow-up	Reported	Side effects / dropouts	Citation
REIMAGINE 1 (Aroda 2026), diet/exercise only, NCT06323174	62 (vs 64 placebo)	Subcutaneous	CagriSema 2.4/2.4 once weekly	40 wk	HbA1c −1.8 vs −0.1; weight −13.8% vs −1.4%	Adverse events 79% vs 66%	PMID 42251860
REIMAGINE 1	63	Subcutaneous	Cagrilintide 1.0 mg + semaglutide 1.0 mg once weekly	40 wk	HbA1c −1.5; weight −11.8%	Adverse events 75%	PMID 42251860
REIMAGINE 2 (Buse 2026), on metformin ± SGLT2i (an SGLT2-inhibitor diabetes pill), NCT06065540	603 (vs 605 semaglutide 2.4 mg)	Subcutaneous	CagriSema 2.4/2.4 once weekly	68 wk	HbA1c −1.91 vs −1.75 (difference −0.16, p=0.0035)	Adverse events 86.9% vs 81.2%; placebo 70.5%	PMID 42251859
REIMAGINE 2	595	Subcutaneous	Cagrilintide 1.0 mg + semaglutide 1.0 mg once weekly	68 wk	Unknown HbA1c not in abstract	Adverse events 81.6%	PMID 42251859
REIMAGINE 3 (Rosenstock 2026), add-on to basal insulin, NCT06323161	90 (vs 91 placebo)	Subcutaneous	CagriSema 2.4/2.4 once weekly	40 wk	HbA1c −2.33 vs −0.66	Adverse events 80% vs 71%; no severe hypoglycaemia	PMID 42251856
REIMAGINE 3	93	Subcutaneous	Cagrilintide 1.0 mg + semaglutide 1.0 mg once weekly	40 wk	HbA1c −2.10; weight −10% to −12% across CagriSema arms	Adverse events 71%; 1 death (malignancy), judged unrelated	PMID 42251856

R14 Human: Heart-outcomes trial (design only)

REDEFINE 3 (Cavender 2026), NCT05669755: 7,076 adults with established cardiovascular disease and BMI 25+, CagriSema 2.4/2.4 vs placebo. Design and baseline only; no outcome results. PMID 42838477

R10, R11, R13 Regulatory (as of Oct 24, 2026)

• R10 Novo Nordisk press release, CagriSema NDA submission, Dec 18, 2025: NDA for chronic weight management based on REDEFINE 1 and 2; "CagriSema is not approved in the US or EU." UNVERIFIED Company source; FDA does not publish pending applications. Novo's REDEFINE 4 release (Feb 23, 2026) says "an FDA decision is anticipated by late 2026."
• R11 FDA, FDA's concerns with unapproved GLP-1 drugs used for weight loss (content current as of Oct 1, 2026): "Retatrutide and cagrilintide cannot be used in compounding under federal law." Checked on fda.gov Oct 24, 2026.
• R13 FDA warning letter, Xcel Research LLC, Dec 10, 2024: "CagriLean" (Cagrilintide and Semaglutide) labeled "FOR RESEARCH USE ONLY" called an unapproved new drug. Checked on fda.gov Oct 24, 2026.
• R9 Novo Nordisk company announcement, REDEFINE 4 headline results, Feb 23, 2026 (SEC Form 6-K). Not peer-reviewed.
• EMA, PMDA, NMPA: UNVERIFIED not checked directly.

Full reference list (all PMIDs verified on PubMed, Oct 24, 2026)

1. Garvey WT, et al. N Engl J Med. 2025;393(7):635-647. doi:10.1056/NEJMoa2502081. PMID 40544433
2. Davies MJ, et al. N Engl J Med. 2025;393(7):648-659. doi:10.1056/NEJMoa2502082. PMID 40544432
3. Yamauchi T, et al. Lancet Diabetes Endocrinol. 2026;14(6):450-462. doi:10.1016/S2213-8587(25)00402-4. PMID 42009015
4. Verma S, et al. Hypertension. 2026;83(2):e26055. doi:10.1161/HYPERTENSIONAHA.125.26055. PMID 41328546
5. Enebo LB, et al. Lancet. 2021;397(10286):1736-1748. doi:10.1016/S0140-6736(21)00845-X. PMID 33894838
6. Aroda VR, et al. Lancet Diabetes Endocrinol. 2026;14(8):649-661. doi:10.1016/S2213-8587(26)00126-9. PMID 42251860
7. Buse JB, et al. Lancet Diabetes Endocrinol. 2026;14(8):662-677. doi:10.1016/S2213-8587(26)00125-7. PMID 42251859
8. Rosenstock J, et al. Lancet. 2026;408(10549):38-51. doi:10.1016/S0140-6736(26)01022-6. PMID 42251856
9. Novo Nordisk A/S. REDEFINE 4 headline results (company announcement), Feb 23, 2026. https://www.sec.gov/Archives/edgar/data/353278/000117184326000996/f6k_022326.htm
10. Novo Nordisk. CagriSema NDA submission press release, Dec 18, 2025. https://www.novonordisk-us.com/media/press-releases/novo-nordisk-cagrisema-fda-nda-submission.html
11. FDA. FDA's concerns with unapproved GLP-1 drugs used for weight loss (content current as of Oct 1, 2026). https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss
12. Frias JP, et al. Lancet. 2023;402(10403):720-730. doi:10.1016/S0140-6736(23)01163-7. PMID 37364590
13. FDA warning letter, Xcel Research LLC (694608), Dec 10, 2024. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/xcel-research-llc-694608-12102024
14. Cavender MA, et al. Am Heart J. 2026 (online Oct 6):107626. doi:10.1016/j.ahj.2026.107626. PMID 42838477
15. WADA. World Anti-Doping Code International Standard: Prohibited List 2026 (in force Jan 1, 2026). https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf (text read Oct 24, 2026)

Disclaimer

This page is for education and harm reduction. It is not medical advice and not a recommendation to use CagriSema, cagrilintide or any blend. Please talk to a clinician you trust before making medical decisions, seek care right away for severe stomach pain or repeated vomiting, and report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).