Description
Pramlintide acetate is an injectable human amylin analog that has been launched for the treatment of both type 1 and type 2 diabetes, in conjunction with insulin. While it is also a 37-amino acid peptide, it differs from its parent predecessor by the substitution of Ala-25, Ser-28, and Ser-29 with prolines. Not only do these modifications improve the solubility of the peptide, they also eliminate the aggregation observed with amylin, resulting in a stable synthetic analog with retention of biological activity that is suitable for pharmaceutical use. As an indication of potency, Pramlintide acetate inhibits the binding of radioiodinated rat amylin to rat nucleus accumbens membranes with a Ki value of 23 pM. Its mechanism of action mimics amylin; as a neurohormone that is cosecreted with insulin from the pancreatic β cells in response to meals, it is involved in glucose homeostasis. Both peptides lower postprandial glucose levels by inhibiting glucagon and by restraining the vagus-mediated rate of gastric emptying, thereby, slowing intestinal carbohydrate absorption. Furthermore, amylin, orPramlintide acetate, has the added benefit of inducing postprandial satiety resulting in weight loss in the patients with type 2 diabetes. Since Pramlintide acetate slows gastric emptying, it is contraindicated in patients with gastroparesis and in patients taking drugs that alter gastrointestinal motility (anticholinergic agents, such as, atropine) or slow down the intestinal absorption of nutrients (such as α-glucosidase inhibitors). Pramlintide acetate is also contraindicated in patients with hypoglycemic tendencies; due to co-administration with insulin, severe insulin-induced hypoglycemia is a risk. The most commonly reported adverse events include nausea, vomiting, anorexia, headache, abdominal pain, fatigue, dizziness, coughing, and pharyngitis.
Clinical Use
Pramlintide acetate is a synthetic analogue of amylin (a 37-peptide) with proline substitutions at
residues 25, 28, and 29. These substitutions change its physical properties such that it is
commercially available for SC injection. When pramlintide is used in combination with insulin, it
slows gastric emptying, lowers blood glucose levels after meals, and affords a feeling of fullness
that leads to decreased caloric intake and the potential for weight loss. Pramlintide has been
approved for use in adults with type I or type II diabetes as an adjunct along with insulin. The
dose is quite different for type I (15–60 μg SC before meals) and type II diabetes (60–120 μg).
The drug should be refrigerated before opening and may be kept at room temperature for up to
28 days after opening.
