Glucagon-like peptide-1 (GLP-1): a trial of treatment in non-insulin-dependent diabetes mellitus.
Glucagon-like peptide-1 (7-36) amide (GLP-1) is released from the gut into the circulation after meals and is the most potent physiological insulinotropic hormone in man. In contrast to presently available therapeutic agents for non-insulin-dependent diabetes mellitus (NIDDM), GLP-1 has the advantages of both suppressing glucagon secretion and delaying gastric emptying. We report the first chronic study of subcutaneous (s/c) GLP-1 treatment in NIDDM. Five patients with poorly controlled NIDDM were entered into a six-week, double-blind crossover trial. Each received three weeks treatment with s/c GLP-1 40 nmol or saline, given three times a day immediately before meals. A standardized test meal was given at the beginning and end of each treatment period. GLP-1 reduced plasma glucose area under the curve (AUC) following the standard test meal by 25% (AUC, 0-180 mins, GLP-1 start of treatment 482.2 +/- 38.2 vs. saline start of treatment 635.7 +/- 45.4 mmol min L-1, F = 16.4, P < 0.02). The beneficial effect of GLP-1 on plasma glucose concentration was fully maintained for the three-week treatment period. Plasma glucagon levels were significantly lower for 60 min postprandially after GLP-1 treatment. In this group of patients there was no significant increase in postprandial insulin levels with GLP-1. We have demonstrated a significant improvement in postprandial glycaemic control with s/c GLP-1 treatment that was fully maintained over a three-week treatment period. GLP-1 improves glycaemic control even in the absence of an insulinotropic effect and is a potential treatment for NIDDM.
Todd
J F
JF
Department of Metabolic Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Wilding
J P
JP
Edwards
C M
CM
Khan
F A
FA
Ghatei
M A
MA
Bloom
S R
SR
D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*
D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon