CagriSema (cagrilintide/semaglutide) — what it does, evidence, and safety

What it is

CagriSema is a once-weekly injectable combination studied for substantial weight loss in adults with obesity — it pairs cagrilintide (a long-acting amylin analogue) and semaglutide (a GLP-1 receptor agonist) in one pen, each dosed. Developed by Novo Nordisk, it is not yet FDA-approved; Novo Nordisk submitted an application in December 2025, though semaglutide on its own is already an approved drug.

What the research found

CagriSema has been studied for weight loss and type 2 diabetes as a combination of cagrilintide and semaglutide. In the Phase 3 REDEFINE 1 trial (adults with obesity, no diabetes), once-weekly CagriSema was associated with about 20.4% average weight reduction at 68 weeks versus about 3.0% on placebo; in REDEFINE 2 (obesity with type 2 diabetes), about 13.7% versus 3.4%, with 73.5% reaching an HbA1c of 6.5% or lower versus 15.9% on placebo. In a head-to-head trial against tirzepatide (REDEFINE 4), Novo Nordisk reported in February 2026 that CagriSema did not meet its primary non-inferiority endpoint; those topline results are not yet peer-reviewed. Gastrointestinal effects were the most common side effects, mostly mild to moderate. The research attributes these weight and blood-sugar changes largely to reduced appetite and food intake (greater satiety via the gut-hormone pathway these agents act on), an appetite and energy-intake mechanism measured across the trials.

Status and regulatory position

Investigational combination (not FDA approved); Novo Nordisk submitted an NDA in December 2025 based on REDEFINE 1, with an FDA decision expected in 2026; components individually relevant (semaglutide approved separately). WADA: not specifically named; as an investigational combination it could fall under S0 (non-approved substances) for tested athletes — verify with your anti-doping organization. Not DEA-scheduled.

Safety

The CagriSema combination is investigational and not FDA-approved; Novo Nordisk submitted an application in December 2025 and an FDA decision is expected in 2026. Its semaglutide component is an approved GLP-1 receptor agonist, and that class carries a boxed warning about thyroid C-cell tumors and is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN2. In the Phase 3 trials, gastrointestinal effects were the most commonly reported and were mostly mild to moderate. The CagriSema combination is not specifically named on the WADA Prohibited List, but as an investigational combination it could fall under the S0 (non-approved substances) category for tested athletes — anyone in regulated sport should verify with their anti-doping organization. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

Disclosures

⚠️ For research and educational purposes only. CagriSema is an investigational combination product not approved by the FDA. Information in this entry is informational, not medical advice. Always confirm any dose figures with the in-app calculator and consult appropriate professional guidance before any decisions.

⚠️ This is a two-component blend. CagriSema combines cagrilintide and semaglutide, each, in one once-weekly subcutaneous injection. Because it is a fixed combination, dosing and any decay/half-life modeling involve two molecules with different pharmacokinetics — they should be considered as overlapping components, not a single agent.

Quick reference

Components	Cagrilintide (long-acting amylin analogue) + semaglutide (GLP-1 receptor agonist)
Frequency	Once weekly, subcutaneous
Half-life — cagrilintide	~159–195 hours (~7–8 days), supporting once-weekly dosing (J Med Chem, "Development of Cagrilintide," DOI 10.1021/acs.jmedchem.1c00565)
Half-life — semaglutide	~165 hours (~7 days) per the semaglutide FDA label (already verified in the semaglutide library entry)
Route	Subcutaneous
Regulatory status	Investigational combination; not FDA-approved. NDA submitted December 18, 2025 (based on REDEFINE 1); FDA decision expected 2026[³]

In depth

CagriSema is an investigational, once-weekly subcutaneous combination of cagrilintide (a long-acting amylin analogue) and semaglutide (a GLP-1 receptor agonist), each dosed, developed by Novo Nordisk. The rationale is to pair two complementary satiety mechanisms — amylin and GLP-1 — in a single weekly injection. The combination product is not yet FDA-approved — Novo Nordisk submitted a New Drug Application on December 18, 2025, based on the REDEFINE 1 trial, with an FDA decision expected during 2026 — although the semaglutide component is independently approved as a standalone GLP-1 drug.[³]

REDEFINE 1 (obesity, no diabetes). According to PubMed, the Phase 3a REDEFINE 1 trial (Garvey et al., NEJM 2025; NCT05567796, n=3417) randomized adults with BMI ≥30, or ≥27 with at least one obesity-related complication and without diabetes, in a 21:3:3:7 ratio to cagrilintide-semaglutide, semaglutide alone, cagrilintide alone, or placebo, over 68 weeks.[¹] The estimated mean percent change in body weight from baseline to week 68 was −20.4% with CagriSema versus −3.0% with placebo (estimated difference −17.3 percentage points; 95% CI −18.1 to −16.6; P<0.001).[¹] Gastrointestinal adverse events affected 79.6% of the CagriSema group versus 39.9% of placebo, and were mainly transient and mild-to-moderate.[¹]

REDEFINE 2 (obesity + type 2 diabetes). According to PubMed, REDEFINE 2 (Davies et al., NEJM 2025; NCT05394519, n=1206) randomized adults with BMI ≥27, HbA1c 7–10%, and type 2 diabetes 3:1 to once-weekly CagriSema ( each) or placebo over 68 weeks.[²] The estimated mean body-weight change from baseline to week 68 was −13.7% with CagriSema versus −3.4% with placebo (estimated difference −10.4 percentage points; 95% CI −11.2 to −9.5; P<0.001).[²] An HbA1c of ≤6.5% was reached by 73.5% of the CagriSema group versus 15.9% of placebo; gastrointestinal adverse events were reported by 72.5% versus 34.4%, mostly transient and mild-to-moderate.[²]

REDEFINE 5 (East Asia). According to PubMed, REDEFINE 5 (Yamauchi et al., Lancet Diabetes & Endocrinology 2026; NCT05813925, n=331) compared co-administered cagrilintide and semaglutide against semaglutide alone in adults in Japan and Taiwan with overweight or obesity, with or without type 2 diabetes.[⁴] Using the trial-product estimand, mean body-weight change at week 68 was −18.4% with CagriSema versus −11.9% with semaglutide alone (estimated difference −6.5 percentage points; 95% CI −8.4 to −4.6; p<0.0001).[⁴]

REIMAGINE program (type 2 diabetes). Three further Phase 3 trials tested the combination in type 2 diabetes. In REIMAGINE 1 (Aroda et al., Lancet Diabetes & Endocrinology 2026; NCT06323174, n=189), in adults inadequately controlled on diet and exercise, HbA1c fell by 1.8 percentage points with CagriSema 2.4/2.4 versus 0.1 with placebo at week 40 (estimated difference −1.7 pp; 95% CI −2.0 to −1.3; p<0.0001), with body-weight change of −13.8% versus −1.4%.[⁵] In REIMAGINE 2 (Buse et al., Lancet Diabetes & Endocrinology 2026; NCT06065540, n=2713), HbA1c fell by 1.91 percentage points with CagriSema versus 1.75 with semaglutide at week 68 (estimated difference −0.16 pp; 95% CI −0.27 to −0.05; p=0.0035), meeting superiority against the active comparator.[⁶] In REIMAGINE 3 (Rosenstock et al., Lancet 2026; NCT06323161, n=274), added to basal insulin, HbA1c fell by 2.33 percentage points versus 0.66 with placebo at week 40 (estimated difference −1.68 pp; 95% CI −1.95 to −1.41; p<0.0001), with body-weight change of roughly −10% to −12% and no severe hypoglycemia reported.[⁷]

REDEFINE 4 (head-to-head vs tirzepatide) — primary endpoint not met. In the REDEFINE 4 trial (NCT06131437, n≈800, 84 weeks), CagriSema 2.4/2.4 was compared directly against tirzepatide in adults with obesity. Novo Nordisk announced topline results on February 23, 2026: participants on CagriSema had roughly 23% body-weight reduction at 84 weeks, but the trial did not meet its primary endpoint of non-inferiority versus tirzepatide.[⁸] No peer-reviewed REDEFINE 4 publication is indexed in PubMed as of the 2026-07-17 check, so these figures are topline company results pending full publication.[⁸] A separate cardiovascular outcomes trial, REDEFINE 3 (NCT05669755, n≈7101, adults with established cardiovascular disease), is active but not recruiting with primary completion scheduled for September 2027, and has not reported results.[⁸]

Reported side effects

Commonly reported

Nausea
Vomiting
Diarrhea
Constipation
Abdominal pain
Gastrointestinal effects overall affected ~72–80% of CagriSema participants in the Phase 3 trials, mainly transient and mild-to-moderate[¹][²]

Serious

Acute pancreatitis symptoms (class concern across incretins)
Gallbladder symptoms
Hypoglycemia — relevant especially in the T2D setting (reported in REDEFINE 2; exact rates not transcribed in this draft)
Severe persistent vomiting or dehydration
Thyroid C-cell tumor risk — class boxed warning associated with the semaglutide/GLP-1 component

Contraindications and warnings

Personal or family history of medullary thyroid carcinoma (MTC) or MEN2 — class contraindication tied to the GLP-1 (semaglutide) component

History of pancreatitis

Severe gastrointestinal disease

Concurrent use of other GLP-1 / amylin / incretin agonists

Pregnancy and lactation: the combination is investigational — no adequate data

Key terms

GLP-1 receptor agonist: A compound that switches on the GLP-1 receptor, the same target a natural gut hormone uses to signal fullness and help regulate blood sugar. Semaglutide is the GLP-1 component of CagriSema.
Amylin: A hormone released with insulin that contributes to feeling full and slows stomach emptying. Cagrilintide, the other half of CagriSema, is a long-acting amylin analogue.
Combination (fixed-dose): A single product that delivers two active compounds together — here, cagrilintide and semaglutide, each, once weekly.
Subcutaneous: Given as an injection into the fatty layer just under the skin, which is how CagriSema is administered.
Investigational: Still being studied and not yet approved by regulators for general use (this applies to the CagriSema combination as a product).

Sources

Related entries

Amycretin — same mechanism class
Dulaglutide — same mechanism class
Exenatide — same mechanism class
Liraglutide — same mechanism class
Mazdutide — same mechanism class
Orforglipron — same mechanism class