Amylin analogues

General information

Amylin is a peptide hormone produced in the beta-cells of the islets of Langerhans and co-secreted with insulin. It has glucoregulatory effects that may complement the actions of insulin.

Pramlintide is an amyloid analogue [ ]. It is administered subcutaneously, but it precipitates above pH 5.5 and therefore cannot be co-administered with insulin. It received FDA approval in 2005 for both type 1 and type 2 diabetes. It reduces postprandial glucose excursions, probably by reducing stomach emptying, not by stimulating the release of glucagon-like peptide (GLP-1) [ ]. It can only be given by injection.

The most common adverse effect of pramlintide is nausea. Hypoglycemia can occur if the dose of insulin is not reduced when pramlintide is added. In no studies was there evidence of cardiac, hepatic, or renal toxicity or hypersensitivity reactions.

Pramlintide has been studied in a double-blind, placebo-controlled, multicenter study in 480 patients with type 1 diabetes for 1 year, followed by an 1-year open extension [ ]. Glucose control improved with pramlintide. Hypoglycemia was less frequent with pramlintide, but nausea and anorexia doubled in frequency and constituted the most common reason for withdrawal.

In a comparable study, 656 patients with type 2 diabetes took preprandial pramlintide 60 micrograms tds, 90 micrograms bd, or 120 micrograms bd [ ]. Only 120 micrograms bd gave a sustained reduction in HbA _1c . In the first 4 weeks there was an increase in the risk of hypoglycemia, but not thereafter. Mild to moderate nausea and headache were the most frequent adverse effects; nausea abated during treatment.

Drug studies