Combination evidence
Cagrilintide + Tirzepatide
Also called Cagri + Tirz, Cagrilintide/Tirzepatide stack
This pairing combines investigational cagrilintide (an amylin analogue) with FDA-approved tirzepatide (a GIP and GLP-1 receptor agonist). No trial giving the two together was found; tirzepatide has appeared in CagriSema trials only as a head-to-head comparator 1. The pairing is therefore theoretical.
Not studied together in humans
Components
What has been studied
- No human study co-administering cagrilintide and tirzepatide was found. Searched: PubMed (cagrilintide AND tirzepatide; amylin AND tirzepatide AND combination) and ClinicalTrials.gov (cagrilintide AND tirzepatide), October 2026.
- The registered trials that include both drugs compare them rather than combine them: CagriSema 2.4 mg/2.4 mg versus tirzepatide 15 mg in obesity (NCT06131437, 809 participants, completed) 1, and CagriSema versus tirzepatide in type 2 diabetes (NCT06221969 and REIMAGINE 5, NCT06534411, both completed) 2 3. No results were posted on the registry records reviewed.
Why the pairing is discussed
Mechanistic reasoning drawn from studies of each component. Theoretical unless a study above tested the pair.
- Theoretical: cagrilintide acts on amylin receptors and reduced body weight as monotherapy in a phase 2 trial 4; tirzepatide's label describes GIP and GLP-1 receptor agonism with reduced food intake and delayed gastric emptying 5. The amylin-plus-incretin rationale comes from the cagrilintide-semaglutide programme 6; it has not been tested with tirzepatide.
Concerns and unknowns
- Both agents increase gastrointestinal adverse events on their own (cagrilintide 41%-63% vs 32% with placebo in phase 2 4); additive gastrointestinal effects would be expected but are unmeasured.
- The Zepbound label warns of severe gastrointestinal adverse reactions, acute kidney injury from volume depletion, acute gallbladder disease, acute pancreatitis and pulmonary aspiration during anaesthesia; it states coadministration with other tirzepatide-containing products or any GLP-1 receptor agonist is not recommended and does not address amylin analogues 5.
- In a SURMOUNT-1 substudy, about 25% of weight lost with tirzepatide was lean mass 7; how an added amylin analogue changes body composition is unknown.
- Cagrilintide has no Drugs@FDA application record (openFDA query, 23 Oct 2026) 8; semaglutide is FDA-approved (Ozempic, Wegovy, Rybelsus). Whether CagriSema has been approved or filed in any jurisdiction was not verified from a regulator source.
- Tirzepatide is not named on WADA's 2026 list; cagrilintide is not named but falls within section S0 wording for drugs under clinical development without governmental approval 9.
Status of each component
| Compound | Regulatory status | Evidence | Half-life |
|---|---|---|---|
| Cagrilintide | Investigational | A | 159 to 195 hours (phase 1b, co-administered with s |
| Tirzepatide | FDA-approved | A | Approximately 5 days (Mounjaro label); approximate |
Frequently asked questions
Has cagrilintide been combined with tirzepatide in a trial?
No. Registered trials compare CagriSema with tirzepatide rather than combining cagrilintide with tirzepatide 1 2 3.
Why is the pairing discussed?
Cagrilintide works on amylin receptors and tirzepatide on GIP and GLP-1 receptors 4 5; an amylin-plus-GLP-1 combination was tested as CagriSema 6, but not this pair.
What would the main overlap be?
Is cagrilintide approved?
References
- CagriSema 2.4 mg/2.4 mg once weekly compared with tirzepatide 15 mg once weekly in participants with obesity (NCT06131437) ClinicalTrials.gov. 2026
- CagriSema 2.4 mg/2.4 mg versus tirzepatide 15 mg in type 2 diabetes on metformin with or without an SGLT2 inhibitor (NCT06221969) ClinicalTrials.gov. 2026
- CagriSema 1.0 mg/1.0 mg versus tirzepatide 5 mg in type 2 diabetes (REIMAGINE 5, NCT06534411) ClinicalTrials.gov. 2026
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial Lancet. 2021
- ZEPBOUND (tirzepatide) injection: prescribing information (Eli Lilly), DailyMed FDA label (DailyMed). 2026
- 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
- Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight Diabetes Obes Metab. 2025
- Drugs@FDA application data queried through openFDA for cagrilintide (no matching application record returned, 23 Oct 2026) openFDA / Drugs@FDA. 2026
- International Standard: Prohibited List 2026 World Anti-Doping Agency. 2026