Pramlintide for the treatment of insulin-requiring diabetes mellitus: rationale and review of clinical data.
Despite a number of incremental, beneficial improvements in diabetes mellitus therapy over the past few decades, the fundamental challenge of replicating the physiological entry into, and uptake of glucose from, the circulation remains unresolved. Pramlintide is an analogue of the beta-cell hormone amylin that simulates its important glucoregulatory actions. In humans, pramlintide slows gastric emptying and suppresses glucagon secretion during the prandial/postprandial period to slow and reduce the entry of glucose into the circulation. These actions, in conjunction with the glucose cellular uptake function of insulin, help normalise fluctuations in circulating glucose levels to a greater degree than is possible with insulin treatment alone. In clinical studies, pramlintide treatment as an adjunct to insulin decreased glycosylated haemoglobin levels (0.39-0.62%) with a concomitant weight loss (0.5-1.4kg) and no significant increase in severe hypoglycaemia. Pramlintide treatment as a potential adjunct to insulin therapy is in late-stage development for patients with type 1 diabetes and insulin-using patients with type 2 diabetes.
Kruger
Davida F
DF
Endocrinology and Metabolism, Henry Ford Health System, 2799 West Grand Boulevard, K-16, Detroit, MI 48202, USA. dkruger1@HFHS.org
Gloster
Maurice A
MA
D000682:Amyloid / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism
D000682:Amyloid; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C105254:pramlintide