The human amylin analog, pramlintide, corrects postprandial hyperglucagonemia in patients with type 1 diabetes

Metabolism. 2002 May;51(5):636-41. doi: 10.1053/meta.2002.32022.


Mealtime amylin replacement with the human amylin analog pramlintide as an adjunct to insulin therapy improves postprandial glycemia and long-term glycemic control in type 1 diabetes. Preclinical animal studies indicate that these complementary effects may result from at least 2 independent mechanisms: a slowing of nutrient delivery to the small intestine and a suppression of nutrient-stimulated glucagon secretion. The former effect of pramlintide has previously been demonstrated in patients with type 1 diabetes. The present studies characterize the effect of pramlintide on postprandial glucagon secretion in this patient population. Plasma glucagon and glucose concentrations were measured before and after a standardized liquid meal in 2 separate randomized, double-blind, placebo-controlled studies of pramlintide administration to patients with type 1 diabetes. In a 2-day crossover study, 18 patients received a 5-hour intravenous infusion of pramlintide (25 microg/h or 50 microg/h) or placebo in addition to subcutaneous (SC) insulin injections. In a 14-day parallel-group study, 84 patients received SC injections of 30, 100, or 300 microg of pramlintide or placebo 3 times daily in addition to SC injections of insulin. In both studies plasma glucagon concentrations increased in response to the meal in the placebo-plus-insulin group but not in any of the pramlintide-treated groups (all pramlintide treatment arms v placebo, P <.05). We conclude that mealtime amylin replacement with pramlintide prevents the abnormal meal-related rise in glucagonemia in insulin-treated patients with type 1 diabetes, an effect that likely contributes to its ability to improve postprandial glucose homeostasis and long-term glycemic control.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Amyloid / administration & dosage
  • Amyloid / therapeutic use*
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Double-Blind Method
  • Fasting
  • Female
  • Food*
  • Glucagon / blood*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Islet Amyloid Polypeptide
  • Kinetics
  • Male
  • Middle Aged
  • Placebos


  • Amyloid
  • Blood Glucose
  • Hypoglycemic Agents
  • Islet Amyloid Polypeptide
  • Placebos
  • Glucagon
  • pramlintide