Cagrilintide

PEPTIDES+ MEMBERS ONLY

INDICATIONS FOR USE

Cagrilintide is used off-label and experimentally for weight management in individuals with overweight or obesity. It is typically prescribed in combination with GLP-1 receptor agonists (e.g., semaglutide) to enhance appetite suppression and promote sustained weight loss. Cagrilintide may also support metabolic health, glycemic control, and long-term weight maintenance in patients undergoing anti-obesity pharmacotherapy.

ROUTE OF ADMINISTRATION

  • Subcutaneous Injection

COMMON INITIAL DOSING REGIMENS

  • Dosing typically begins at 0.1 mg subcutaneously once weekly and may be titrated upward by 0.1–0.2 mg weekly to a target dose of 1.2–2.4 mg weekly based on tolerance and clinical response. In combination regimens with semaglutide, slower titration may be used to minimize gastrointestinal side effects.

MECHANISM OF ACTION

  • Cagrilintide is an amylin receptor agonist that mimics the activity of human amylin, a hormone co-secreted with insulin by pancreatic beta cells. Amylin slows gastric emptying, reduces glucagon secretion, and promotes satiety by acting on the brain’s appetite-regulating centers, particularly the area postrema and nucleus tractus solitarius. Cagrilintide has a long half-life and extended duration of action, enabling once-weekly dosing. When combined with GLP-1 receptor agonists, it can synergistically enhance weight loss by acting on complementary pathways involved in appetite regulation and energy intake.

COMMON SIDE EFFECTS

  • Gastrointestinal: Nausea, vomiting, constipation, or early satiety, especially during dose titration.

  • General: Fatigue, dizziness, or mild headache.

  • Metabolic: Hypoglycemia is rare when used alone but may occur if combined with insulin or sulfonylureas.

  • Injection Site: Redness, swelling, or discomfort.

  • Rare: Delayed gastric emptying may complicate the absorption of other oral medications.

CONTRAINDICATIONS

  • Absolute: Known hypersensitivity to cagrilintide or related compounds. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2), due to theoretical risks associated with long-acting amylin receptor agonists.

  • Relative: Use with caution in patients with severe gastrointestinal disorders (e.g., gastroparesis) or those at risk for hypoglycemia when used in combination with other glucose-lowering agents.

COMPARISON WITH OTHER AGENTS

  • Semaglutide: A GLP-1 receptor agonist that slows gastric emptying and suppresses appetite. When used in combination with cagrilintide, greater total weight loss may occur due to synergistic appetite suppression.

  • Tirzepatide: A dual GLP-1/GIP receptor agonist that also impacts appetite and insulin sensitivity. Cagrilintide may offer an additive effect when used with GLP-1-only agents but has not been well studied in combination with tirzepatide.

  • 5-Amino 1MQ: Works through metabolic modulation rather than appetite suppression. Cagrilintide targets central satiety pathways.

EXPERIMENTAL TREATMENT DISCLAIMER:

  • Cagrilintide is not currently approved by the FDA for weight loss or any other indication in the United States. Its use is considered experimental. While clinical trials have demonstrated promising weight loss outcomes, long-term safety and efficacy data in large populations are limited. The patient acknowledges the investigational nature of this treatment and agrees to proceed with full understanding of the associated risks and unknowns.

MORE INFORMATION

  • FDA Safety Data Sheet not available (experimental peptide).

  • Frias JP. 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 [PubMed Link]

  • D'Ascanio AM. Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. Cardiol Rev. 2024 [PubMed Link]

  • Lau DC. 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 [PubMed Link]

  • Enebo LB. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021 [PubMed Link]

  • Garvey WT. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2025 [PubMed Link]

  • Kruse T. Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem. 2021 [PubMed Link]

  • Davies MJ. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med. 2025 [PubMed Link]

  • Dutta D. Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide (Cagrisema) as Anti-Obesity Medications: A Systematic Review and Meta-Analysis. Indian J Endocrinol Metab. 2024 [PubMed Link]

  • Becerril S. Cagrilintide plus semaglutide for obesity management. Lancet. 2021 [PubMed Link]

  • Ryan DH. Drugs for Treating Obesity. Handb Exp Pharmacol. 2022 [PubMed Link]

  • Bailey CJ. An update on peptide-based therapies for type 2 diabetes and obesity. Peptides. 2023 [PubMed Link]

  • Gogineni P. Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? Expert Opin Pharmacother. 2024 [PubMed Link]

  • Sidrak WR. Approved and Emerging Hormone-Based Anti-Obesity Medications: A Review Article. Indian J Endocrinol Metab. 2024 [PubMed Link]

  • Abdalla Ahmed MA. Advancements in the management of obesity: a review of current evidence and emerging therapies. Expert Rev Endocrinol Metab. 2024 [PubMed Link]