Pramlintide in the treatment of type 1 and type 2 diabetes mellitus.
BACKGROUND
Amylin is a 37-amino acid peptide neurohormone that is cosecreted with insulin from the pancreatic beta cells in response to meals. It lowers serum glucose by decreasing glucagon release, slowing gastric emptying, and decreasing food intake. Pramlintide, a synthetic amylin analogue, is approved by the US Food and Drug Administration for use with mealtime insulin in patients with type 1 diabetes and patients with type 2 diabetes who are using mealtime insulin only or the combination of insulin and metformin and/or a sulfonylurea.


OBJECTIVE
This article reviews the available literature on pramlintide with respect to its mechanism of action, pharmacokinetics and pharmacodynamics, clinical efficacy in type 1 and type 2 diabetes, safety and tolerability, dosing, contraindications, and drug interactions.


METHODS
MEDLINE (1966-April 2005), Iowa Drug Information Service (1966-April 2005), and International Pharmaceutical Abstracts (1970-April 2005) were searched for clinical trials and therapeutic reviews published in the English language. The search terms were pramlintide and amylin. The bibliographies of identified articles were reviewed for additional references. All relevant studies were included in the review.


RESULTS
Six studies, ranging in duration from 4 to 52 weeks, examined the effect of administering pramlintide with premeal insulin in patients with type 1 diabetes. In these trials, pramlintide 120 to 270 microg/d reduced glycosylated hemoglobin (HbA(1c)) by 0.1 % to 0.67%, 1-hour postprandial glucose (PPG) by 4.4 to 7 mmol/L, and 2-hour PPG by 3.6 to 4.8 mmol/L. Five studies, also ranging from 4 to 52 weeks' duration, examined the effect of administering premeal pramlintide in patients with type 2 diabetes. In these trials, pramlintide 90 to 450 microg/d reduced HbA(1c) by 0.3% to 0.62%, 1-hour PPG by 4.8 mmol/L, and 2-hour PPG by 3.4 mmol/L. The principal adverse events reported in clinical trials were nausea and hypoglycemia. The incidence of hypoglycemia in the first 4 weeks of therapy was 2 to 4 times greater with pramlintide compared with placebo; thus, the manufacturer recommends reducing the dose of premeal insulin by 50% when starting pramlintide. Close monitoring of blood glucose levels is recommended when initiating pramlintide therapy.


CONCLUSIONS
Use of pramlintide in addition to insulin in patients with type 1 and type 2 diabetes was associated with modest reductions in HbA(1c). The primary adverse effects of pramlintide therapy were nausea and hypoglycemia.
Ryan
Gina J
GJ
Clinical and Administrative Sciences, Southern School of Pharmacy, Mercer University, Atlanta, GA 30341, USA. ryan_gj@mercer.edu
Jobe
Lynetta J
LJ
Martin
Rhonda
R
D000682:Amyloid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005934:Glucagon / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage; D058228:Islet Amyloid Polypeptide; D019518:Postprandial Period
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005934:Glucagon; C105254:pramlintide