Pramlintide

Pramlintide is a synthetic amylin analogue given by subcutaneous injection before major meals as an add-on to mealtime insulin in type 1 and type 2 diabetes. It lowers HbA1c by about 0.3 to 0.6% and body weight by 1 to 2 kg, mainly by reducing post-meal glucose rise. It carries a boxed warning for severe insulin-induced hypoglycaemia and is not marketed in many countries.

Classification. Amylin analogue. Pen injectors of 60 and 120 micrograms a dose in the markets where it is available.

Mechanism. Mimics amylin, co-secreted with insulin by beta cells. It slows gastric emptying, suppresses post-meal glucagon release and increases satiety through central action.

Pharmacodynamics. Reduces the post-meal glucose rise and lessens weight gain from insulin. It does not stimulate insulin release, so hypoglycaemia arises from insulin.

Pharmacokinetics. Subcutaneous bioavailability about 30 to 40%; peak about 20 minutes; duration about 3 hours. Metabolised and cleared mainly by the kidney to an active metabolite. Half-life about 48 minutes.

Type 1 diabetes, adults, with mealtime insulin.

• Start 15 micrograms subcutaneously immediately before each major meal (at least 250 kcal or 30 g carbohydrate).
• Increase by 15 micrograms every 3 days if there is no significant nausea, to 30 micrograms, then 45 micrograms, then a maximum of 60 micrograms before each major meal.
• If nausea persists at a dose, return to the previous tolerated dose.
• Reduce rapid-acting or short-acting mealtime insulin by 50% when starting; later adjust insulin to glucose readings.

Type 2 diabetes, adults, on mealtime insulin with or without metformin or a sulphonylurea.

• Start 60 micrograms subcutaneously immediately before each major meal.
• After 3 to 7 days, increase to 120 micrograms before each major meal if there is no significant nausea for 3 to 7 days.
• Maximum 120 micrograms a dose. Reduce mealtime insulin by 50% when starting.

Missed doses. Omit the dose if the meal is skipped or contains under 250 kcal or under 30 g carbohydrate.

Adjustments.

• Kidney: no change in mild to moderate impairment (creatinine clearance 20 to 80 mL/min); not studied in dialysis.
• Liver: no change.
• Older adults: no change; start low.
• Weight: no weight-based dosing.
• Children: not licensed.

Boxed-warning-level risk. Severe hypoglycaemia, mostly within 3 hours of injection, especially in type 1 diabetes and when insulin is not reduced at the start. Patients need to be selected carefully, and mealtime insulin cut by half on starting.

Contraindications. Gastroparesis; hypoglycaemia unawareness; hypersensitivity; use of drugs that stimulate gut motility.

Common adverse effects. Nausea (about 30 to 50% early), vomiting, anorexia, abdominal pain, headache, fatigue; fade over 2 to 4 weeks.

Major interactions.

• Insulin: hypoglycaemia; reduce the mealtime dose by 50% on starting.
• Anticholinergics and other drugs that slow gastric motility: avoid.
• Oral medicines needing rapid absorption (analgesics, antibiotics): take at least 1 hour before, or 2 hours after, pramlintide.
• Alpha-glucosidase inhibitors: avoid in combination.

Special groups.

• Pregnancy: avoid; no human data.
• Breastfeeding: avoid.
• Children: not licensed.
• Older adults: hypoglycaemia and nausea limit use.
• Kidney and liver impairment: no change in mild to moderate kidney impairment; not studied in dialysis; no liver adjustment.
• East Africa: not available; insulin optimisation is the practical route.

Administration. Inject subcutaneously into the abdomen or thigh immediately before major meals, in a different site from the insulin injection (at least 5 cm apart). Never mix with insulin in the same syringe. Store unopened pens in a fridge (2 to 8 degrees Celsius); an opened pen keeps at room temperature up to 30 degrees Celsius for 30 days.

Baseline. HbA1c, eGFR, hypoglycaemia history, gastric emptying symptoms, capillary glucose pattern.

Monitoring.

• Capillary glucose before and 2 hours after meals and at bedtime during titration.
• HbA1c at 3 and 6 months, then every 6 months.
• Weight and nausea at each visit.

Stopping thresholds. Stop with recurrent severe hypoglycaemia, persistent severe nausea, development of gastroparesis, or HbA1c reduction under 0.3% at 6 months.

Referral and escalation. Admit severe hypoglycaemia (treat with intravenous glucose 10%, or glucagon 1 mg intramuscularly if no intravenous access). Refer to a diabetes specialist for recurrent hypoglycaemia.