Pramlintide in the treatment of diabetes mellitus

Abstract

Pramlintide, the first member of a new class of drugs for the treatment of insulin-using patients with type 2 or type 1 diabetes mellitus, is an analog of the peptide hormone amylin. Amylin is co-secreted with insulin from pancreatic beta cells and acts centrally to slow gastric emptying, suppress postprandial glucagon secretion, and decrease food intake. These actions complement those of insulin to regulate blood glucose concentrations. Amylin is relatively deficient in patients with type 2 diabetes, depending on the severity of beta-cell secretory failure, and is essentially absent in patients with type 1 diabetes. Through mechanisms similar to those of amylin, pramlintide improves overall glycemic control, reduces postprandial glucose levels, and reduces bodyweight in patients with diabetes using mealtime insulin. Reductions in postprandial glucose and bodyweight are important, since postprandial hyperglycemia is associated with an increased risk of microvascular and macrovascular complications, and increased weight is an independent risk factor for cardiovascular disease. Pramlintide is generally well tolerated, with the most frequent treatment-emergent adverse event being mild to moderate nausea, which decreases over time. Pramlintide treatment is also associated with improvements in markers of oxidative stress and cardiovascular risk and improved patient-reported treatment satisfaction. These factors make pramlintide an attractive option for the treatment of postprandial hyperglycemia in patients with diabetes using mealtime insulin.