Reference vials: Cagrilintide, Semaglutide

Combination evidence

CagriSema (cagrilintide + semaglutide)

Also called CagriSema, cagrilintide-semaglutide

CagriSema is Novo Nordisk's once-weekly combination of cagrilintide, a long-acting amylin analogue, with semaglutide, a GLP-1 receptor agonist. Unlike most combinations on Amiravo, it has been given to humans in randomised phase 1b, phase 2 and phase 3 trials (REDEFINE and REIMAGINE programmes) ¹ ³ ^6. Cagrilintide itself is not FDA-approved ^12.

Tested together in human trials

Components

Cagrilintide
Investigational
Human amounts: see dosing page
Dosing reference
Semaglutide
FDA-approved
Human amounts: see dosing page
Dosing reference

What has been studied

Phase 1b (NCT03600480): 96 otherwise healthy adults with BMI 27.0-39.9 were randomised to cagrilintide or placebo, each with semaglutide; gastrointestinal disorders made up 37% of 566 adverse events, cagrilintide exposure did not affect semaglutide exposure or elimination, and at week 20 weight reductions were larger with cagrilintide 1.2 and 2.4 mg than with placebo (15.7% and 17.1% vs 9.8%), all with semaglutide ^1.
Phase 2 in type 2 diabetes (NCT04982575, 32 weeks, n=92): HbA1c change was -2.2 percentage points with CagriSema, -1.8 with semaglutide and -0.9 with cagrilintide (CagriSema vs semaglutide not significant, p=0.075); body-weight change was -15.6%, -5.1% and -8.1% ^2.
REDEFINE 1 (NCT05567796, phase 3a, 68 weeks, 3,417 adults without diabetes): estimated mean body-weight change was -20.4% with cagrilintide-semaglutide versus -3.0% with placebo; gastrointestinal adverse events affected 79.6% versus 39.9% ^3.
REDEFINE 2 (NCT05394519, phase 3a, 68 weeks, 1,206 adults with type 2 diabetes): body-weight change was -13.7% versus -3.4% with placebo; gastrointestinal adverse events were reported by 72.5% versus 34.4% ^4.
REDEFINE 5 (NCT05813925, Japan and Taiwan, 68 weeks, n=331): body-weight change was -18.4% with cagrilintide-semaglutide versus -11.9% with semaglutide alone; gastrointestinal disorders occurred in 53% versus 51% ^5.
REIMAGINE 1, 2 and 3 (type 2 diabetes; diet and exercise, metformin with or without SGLT2 inhibitor, and basal insulin respectively) reported larger HbA1c reductions than placebo; in REIMAGINE 2 the HbA1c difference versus semaglutide 2.4 mg was -0.16 percentage points (p=0.0035) ⁷ ⁶ ^8.
REDEFINE 3 (NCT05669755) is a cardiovascular outcomes trial that randomised 7,076 adults with established cardiovascular disease and BMI of at least 25; its design and baseline data were published in 2026 and outcome results were not identified ^9.

Doses given in the trials

What investigators administered in each cited trial, recorded as facts about those studies.

Phase 1b (NCT03600480): participants received once-weekly subcutaneous cagrilintide 0.16, 0.30, 0.60, 1.2, 2.4 or 4.5 mg or placebo (3:1 within six sequential cohorts), each combined with once-weekly subcutaneous semaglutide 2.4 mg; doses were co-escalated at 4-week intervals over 16 weeks, held at target for 4 weeks, followed by 5 weeks of follow-up ^1.
Phase 2 (NCT04982575): adults with type 2 diabetes on metformin with or without an SGLT2 inhibitor were randomised 1:1:1 to once-weekly subcutaneous CagriSema, semaglutide or cagrilintide, all escalated to 2.4 mg, for 32 weeks ^2.
REDEFINE 1 (NCT05567796): participants were randomised 21:3:3:7 to cagrilintide 2.4 mg plus semaglutide 2.4 mg, semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone, or placebo, once weekly, plus lifestyle intervention, for 68 weeks ^3.
REDEFINE 2 (NCT05394519): adults with type 2 diabetes were randomised 3:1 to once-weekly cagrilintide-semaglutide (2.4 mg each) or placebo, with lifestyle intervention, for 68 weeks ^4.
REDEFINE 5 (NCT05813925): participants were randomised 1:1 to once-weekly subcutaneous fixed-dose cagrilintide-semaglutide or semaglutide, both escalated to 2.4 mg, plus lifestyle intervention, for 68 weeks ^5.
REIMAGINE 1 (NCT06323174): adults with type 2 diabetes on diet and exercise were randomised 2:1:2:1 to once-weekly cagrilintide 2.4 mg plus semaglutide 2.4 mg, matching placebo, cagrilintide 1.0 mg plus semaglutide 1.0 mg, or matching placebo, for 40 weeks ^7.
REIMAGINE 2 (NCT06065540): participants were randomised 8:8:2:8:8:1:1 to once-weekly cagrilintide-semaglutide 2.4 mg each, semaglutide 2.4 mg, cagrilintide 2.4 mg, cagrilintide-semaglutide 1.0 mg each, semaglutide 1.0 mg, or corresponding placebo, for 68 weeks ^6.
REIMAGINE 3 (NCT06323161): adults on basal insulin were randomised 2:2:1:1 to once-weekly cagrilintide-semaglutide 2.4 mg each, 1.0 mg each, or dose-matched placebo, for 40 weeks ^8.

Why the pairing is discussed

Mechanistic reasoning drawn from studies of each component. Theoretical unless a study above tested the pair.

Mechanistic background (component-level, the reason the pair was developed): native amylin is a pancreatic hormone that induces satiety, and cagrilintide is a long-acting amylin analogue that reduced body weight as monotherapy in a phase 2 trial in people with overweight or obesity ^10.
Mechanistic background: semaglutide is a GLP-1 receptor agonist; its label describes glucose-dependent insulin secretion, lower glucagon secretion, a minor delay in early postprandial gastric emptying, and GLP-1 receptors in brain areas involved in appetite regulation ^11.
Theoretical framing in trial reports: REIMAGINE 2 investigators describe the two agents as having complementary effects on glycaemic control and body weight ^6; in the phase 2 diabetes trial, CagriSema produced larger weight change than either component, while the HbA1c difference versus semaglutide was not significant ^2.

Concerns and unknowns

Gastrointestinal adverse events (nausea, vomiting, diarrhoea, constipation, abdominal pain) were the most common class in CagriSema trials, affecting 79.6% versus 39.9% with placebo in REDEFINE 1 ^3; cagrilintide alone also increased gastrointestinal events versus placebo in its phase 2 trial (41%-63% vs 32%) ^10.
The Wegovy label warns of acute pancreatitis, acute gallbladder disease, hypoglycaemia with insulin or insulin secretagogues, diabetic retinopathy complications, heart-rate increase and pulmonary aspiration during anaesthesia, and states that concomitant use with other semaglutide-containing products or any other GLP-1 receptor agonist is not recommended ^11.
Cagrilintide has no Drugs@FDA application record (openFDA query, 23 Oct 2026) ^12; semaglutide is FDA-approved (Ozempic, Wegovy, Rybelsus). Whether CagriSema has been approved or filed in any jurisdiction was not verified from a regulator source.
Trial results apply to the trial products and populations; compounded or research-grade cagrilintide and semaglutide sold separately are not the products tested.
Neither cagrilintide nor semaglutide is named on WADA's 2026 list; section S0 covers drugs under clinical development with no current governmental approval, which would apply to cagrilintide unless it is approved somewhere ^13.

Status of each component

Compound	Regulatory status	Evidence	Half-life
Cagrilintide	Investigational	A	159 to 195 hours (phase 1b, co-administered with s
Semaglutide	FDA-approved	A	Approximately 1 week; present in the circulation f

Frequently asked questions

What is CagriSema?

A once-weekly combination of cagrilintide (amylin analogue) and semaglutide (GLP-1 receptor agonist) developed by Novo Nordisk and tested in phase 3 trials ¹ ^3.

What did the phase 3 obesity trial find?

In REDEFINE 1, estimated mean body-weight change at 68 weeks was -20.4% with cagrilintide-semaglutide versus -3.0% with placebo ^3.

Is CagriSema FDA-approved?

No Drugs@FDA record for cagrilintide was found as of 23 October 2026 ^12. Semaglutide alone is approved.

What were the main side effects in trials?

Mostly gastrointestinal events, reported as mainly transient and mild to moderate, and more frequent than with placebo ³ ^4.

Does combining it with other GLP-1 drugs make sense?

The Wegovy label states that concomitant use with any other GLP-1 receptor agonist is not recommended ^11.

Is CagriSema better than semaglutide alone?

In REDEFINE 5, weight change was larger with the combination (-18.4% vs -11.9%) ^5; in REIMAGINE 2 the HbA1c difference versus semaglutide was -0.16 percentage points ^6.

References

All combinations Compare the components side by side