The combination metformin/glyburide exerts its hypoglycemic effect mainly by increasing insulin secretion: a controlled, randomized, double-blind, crossover study.
The aim of the present study was to describe the mechanism by which the combination glyburide/metformin exerts its additive hypoglycemic effects. This is a double-blind, randomized and crossover clinical trial. Patients (n = 20) were included in a run-in period of 8 weeks in which an isocaloric diet was prescribed. If they did not achieve the treatment goals (n = 15), they received glyburide, metformin or combined treatment for 10 weeks each using three possible sequences. The dosage was adjusted to reach fasting plasma glucose (FPG) < 7.7 mmol/l. Treatment periods were separated by a 6-12 week washout period. At the beginning and the end of every treatment, insulin sensitivity and insulin secretion were measured by means of a minimal model and an oral glucose tolerance test. All treatment periods were completed by 12 cases. The glycemic goal was reached in 1 case during metformin, in 5 during glyburide and in 10 during the combination. The greatest reduction in HbA1c was achieved during the combination (HbA1c 11 +/- 1.6 vs 9.8 +/- 1.9 vs 9.0 +/- 2.1% for metformin, glyburide and the combination, p < 0.001). Increased insulin secretion was the explanation for the additive effects of the combination (percentual change in acute insulin response during the minimal model = 5.8 vs 51.5 vs 88.2% for metformin, glyburide and the combination, p < 0.05). No change in insulin sensitivity resulted from the treatments. In conclusion, the additive hypoglycemic effects of the combination glyburide/metformin was caused by increased insulin secretion.
Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, Mexico City.
A
A
Gulias-Herrero
C A
CA
Aguilar-Salinas
F J
FJ
Gómez-Pérez
J A
JA
Rull
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome
D001786:Blood Glucose; D004338:Drug Combinations; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; C417231:Glucovance