Effect of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor, on glucose, insulin, C-peptide and GIP responses to an oral sucrose load in patients with post-prandial hypoglycaemic symptoms.
Sixteen patients suffering from symptoms suggestive of idiopathic reactive hypoglycaemia and reproducible during an oral glucose tolerance test when plasma glucose was less than or equal to 2.8 mM, were included in an acute, double-blind and cross-over study to test the efficacy of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor versus placebo. Patients were randomized to ingest 100 mg Miglitol or placebo together with a sucrose solution (45 g/m2 body surface), one week apart. During four hours, plasma glucose levels were continuously monitored and plasma insulin and gastric inhibitory polypeptide (GIP) levels were measured at 30-minute intervals; serum C-peptide concentration was determined at 0, 30, 60 minutes and then every hour. The post-load rise in plasma glucose was significantly blunted by Miglitol, as shown by the reduced plasma glucose peak, the diminished early (0-120 min) area under the glycaemic curve and the decreased rate of plasma glucose rise. Thereafter, plasma glucose nadir was significantly raised and rate of plasma glucose fall was slowed by Miglitol with a concomitant improvement in the hypoglycaemic index. Insulin secretion was dampened as indicated by parallel reduction of plasma insulin and serum C-peptide peaks; morever, early area under the insulin curve and total (0-240 min) area under the C-peptide curve were significantly reduced. Decrease of plasma GIP peak and total area under the GIP curve were also significant. During sucrose tolerance test with Miglitol, hypoglycaemic symptoms were significantly alleviated but intestinal side-effects were common. Blunting the insulin response to glucose directly by delaying glucose absorption and indirectly through reducing GIP secretion, may be a valuable therapeutic approach in reactive hypoglycemia; nevertheless, long-term study with Miglitol are needed, due to the poor intestinal tolerance of this drug in the present acute study.
Renard
E
E
Clinique des Maladies métaboliques et endocriniennes, Hôpital Lapeyronie, Montpellier, France.
Parer-Richard
C
C
Richard
J L
JL
Jureidini
S
S
Orsetti
A
A
Mirouze
J
J
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000284:Administration, Oral; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005951:Glucose Tolerance Test; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007003:Hypoglycemia / Q000097:blood*; D050112:Imino Pyranoses; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013395:Sucrose / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D002096:C-Peptide; D065089:Glycoside Hydrolase Inhibitors; D050112:Imino Pyranoses; D007328:Insulin; C045621:miglitol; D017485:1-Deoxynojirimycin; D013395:Sucrose; D005749:Gastric Inhibitory Polypeptide; D005944:Glucosamine