Amylin Analogues

Amylin analogues are injectable peptides that replace the action of amylin, a hormone co-secreted with insulin from beta cells. Pramlintide is the licensed agent in type 1 and type 2 diabetes treated with mealtime insulin, and newer long acting amylin analogues (cagrilintide) are being developed for obesity, often in combination with semaglutide.

Mechanism. Amylin receptor agonism suppresses postprandial glucagon secretion, slows gastric emptying and promotes satiety through the area postrema. The combined effect lowers postprandial glucose and body weight.

Pharmacokinetics. Pramlintide is injected subcutaneously before meals, with a half-life of about 48 minutes and effect lasting 3 hours. Cagrilintide is a long acting weekly analogue.

Pramlintide. Limited availability and withdrawn from some markets. Not mixed in a syringe with insulin because of pH.

Cagrilintide. Weekly injection, investigational alone or with semaglutide for weight management. Regulatory status varies, so confirm local availability.

Versus GLP-1 receptor agonists. Different receptor target; short acting pramlintide requires injection with each meal and has less cardiovascular and weight evidence.

• Type 1 diabetes: start pramlintide 15 micrograms before meals, increase by 15 micrograms every 3 days if nausea is absent, to 30 to 60 micrograms. Reduce mealtime insulin by 50% when starting to avoid severe hypoglycaemia.
• Type 2 diabetes on mealtime insulin: start 60 micrograms before major meals (at least 250 kcal or 30 g carbohydrate), increase to 120 micrograms after 3 to 7 days if tolerated.
• Skipped meal: omit the dose.
• Selection: postprandial excursions despite optimal insulin, with weight gain. Used rarely.

Special groups. Pregnancy: avoid. Breastfeeding: avoid. Children: not licensed. Older adults: use with caution. Kidney impairment: no adjustment unless severe. Liver impairment: caution.

Adverse effects. Nausea, anorexia, vomiting, headache, and severe hypoglycaemia within 3 hours, particularly in type 1 diabetes.

Contraindications. Gastroparesis, hypoglycaemia unawareness, and a history of recurrent severe hypoglycaemia.

Interactions. Slows gastric emptying and alters absorption of oral drugs that need a rapid onset: give those at least 1 hour before or 2 hours after the injection. Anticholinergics and other drugs slowing gastric motility compound this.

Monitoring. Glucose before and 2 hours after meals during titration, weight, and nausea.

Referral and escalation. Recurrent severe hypoglycaemia, persistent vomiting, or planned use in type 1 diabetes, which is a specialist decision.