Cagrilintide

a long synthetic amylin/CGRP analogue

Key Benefits

Appetite Suppression & Weight Loss

Cagrilintide is a dual amylin‑ and calcitonin‑receptor agonist that slows gastric emptying, reduces food intake via homeostatic and hedonic brain centers, and leads to ~9–11% weight loss at 2.4 mg/week, rising to ~17% when combined with semaglutide

Synergistic Metabolic Effects

In combination (CagriSema), weight loss reached ~17–22% in trials, with better glycemic control (HbA1c reductions ~2.2%) versus monotherapy — showing additive mechanisms of amylin + GLP‑1

Improved Glycemic Control

For T2D patients, cagrilintide + semaglutide cut HbA1c by ~2.2%, fasting glucose by ~3.3 mmol/L, significantly outperforming either alone

Potential Cardiometabolic Benefits

Preclinical models suggest enhanced cardiovascular outcomes (e.g., blood pressure, lipid metabolism), liver protection, and possible benefits for liver/alcohol‑related disease

Biologic Description

Cagrilintide is a long‑acting amylin analogue engineered to resist proteolytic degradation and extend half‑life. It's a dual amylin and calcitonin receptor agonist (DACRA). Modeled on human amylin, it slows gastric emptying and signals satiety via brainstem/hypothalamus.

It has been tested both as monotherapy and in combination with semaglutide (GLP‑1 RA). Monotherapy delivers significant weight reduction; combination (CagriSema) achieves up to ~22.7% weight loss over 68 weeks with enhanced glycemic control.

Dosage Guidelines

Weekly subcutaneous dosing with gradual titration is the standard protocol. Combination trials follow this protocol over 16 weeks before adding semaglutide → maintenance at 2.4 mg/week. Higher 4.5 mg dose explored in Phase 2 weight-loss trial :

100-250mcg

Weekly

1-4 Weeks

300-500mcg

Weekly

5-8 Weeks

600-1000mcg

Weekly

9-12 Weeks

1100-1700mcg

Weekly

13-16 Weeks

1800-2400mcg

Weekly

17+ Weeks

Side Effects

Generally well tolerated; most common side effects are gastrointestinal and injection-site-related:

Nausea (up to ~47%)
Vomiting (~8%), indigestion, constipation, loose stools (~7%)
Headache (~7%)
Injection-site reactions (~43%)
Fatigue (~20%)
Allergic reactions (~10%)

Serious adverse events <10%, discontinuation ~6–10%. One gallstone case noted. Side effects typically mild to moderate and diminish over time.

References:

Kruse, T., Hansen, J. L., Dahl, K., Schäffer, L., Sensfuss, U., Poulsen, C., Schlein, M., Hansen, A. M. K., Jeppesen, C. B., Dornonville de la Cour, C., Clausen, T. R., Johansson, E., Fulle, S., Skyggebjerg, R. B., & Raun, K. (2021). Development of cagrilintide, a long‑acting amylin analogue. Journal of Medicinal Chemistry, 64(15), 11183–11194. https://doi.org/10.1021/acs.jmedchem.1c00565
ClinicalTrials.
Frias, J. P., Deenadayalan, S., Erichsen, L., Knop, F. K., & Lingvay, I. (2023). 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, randomized, double‑blind, active‑controlled, phase 2 trial. The Lancet, 402(10403), 720–730. https://doi.org/10.1016/S0140‑6736(23)01163‑7
Garvey, W. T., Blüher, M., Osorto Contreras, C. K., Davies, M. J., & Lehmann, E. W. (2025). Coadministered cagrilintide and semaglutide in adults with overweight or obesity. New England Journal of Medicine. Advance online publication. https://doi.org/10.1056/NEJMoa2502081
Davies, M. J., Bajaj, H. S., Broholm, C., Eliasen, A., & Garvey, W. T. (2025). Cagrilintide–semaglutide in adults with overweight or obesity and type 2 diabetes. New England Journal of Medicine. Advance online publication.
Garvey, W. T., Blüher, M., et al. (2025). Greater weight loss with combined cagrilintide‑semaglutide vs semaglutide alone: results from REDEFINE‑1 and REDEFINE‑2. Journal Scan, American College of Cardiology.
Cho, S., & Andersen, F. (2022). Does receptor balance matter? Comparing the efficacies of the dual amylin and calcitonin receptor agonists cagrilintide and KBP‑336 on metabolic parameters in preclinical models. Biomedicine & Pharmacotherapy, 162, 114273.
Nature Communications. (2025). Structural and dynamic features of cagrilintide binding to calcitonin‑family receptors. Nature Communications.

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