The human amylin analog, pramlintide, corrects postprandial hyperglucagonemia in patients with type 1 diabetes.
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.
Fineman
M S
MS
Clinical Science, Amylin Pharmaceuticals Inc., 9373 Towne Centre Drive, San Diego, CA 92121, USA.
Koda
J E
JE
Shen
L Z
LZ
Strobel
S A
SA
Maggs
D G
DG
Weyer
C
C
Kolterman
O G
OG
D000293:Adolescent; D000328:Adult; D000682:Amyloid / Q000008:administration & dosage / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D005502:Food; D005934:Glucagon / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010919:Placebos
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D010919:Placebos; D005934:Glucagon; C105254:pramlintide