Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients.
The objective of this study was to determine the safety, efficacy, and tolerability of the alpha-glucosidase inhibitor miglitol vs. the sulfonylurea glyburide in the treatment of elderly patients with type 2 diabetes mellitus, inadequately controlled by diet alone. This was a double-blind, randomized, placebo-controlled, 1-yr trial of miglitol 25 mg TID and 50 mg TID compared with placebo and a titrated dose of glyburide in a parallel group comparison study conducted in 30 out-patient sites across the United States. Four hundred eleven (411) diet-treated patients age 60 yr or greater were randomized to receive either placebo TID (n = 101), miglitol 25 mg TID (n = 104), miglitol 50 mg TID (n = 102), or a once-daily dose of glyburide titrated based on fasting plasma glucose (FPG) (n = 104), for a period of 56 weeks. Efficacy was assessed by glycated hemoglobin (HbA1c), fasting and post-meal glucose, insulin, and lipid levels, and by 24-h urinary excretion of glucose and albumin. Safety and tolerability were assessed by tabulation of adverse events, periodic laboratory determinations, and home blood glucose monitoring. HbA1c treatment effects (placebo-subtracted change in HbA1c from baseline) at the 1-yr endpoint were -0.49%, -0.40%, and -0.92% in the miglitol 25 mg TID, miglitol 50 mg TID, and glyburide groups, respectively (P < 0.05- 0.01 vs. placebo). Postprandial insulin levels were significantly greater than placebo and miglitol in the glyburide group (P < 0.01). Hypoglycemia, weight gain, and both routine and serious cardiovascular events were more frequent in the glyburide group (P < 0.05-0.01 vs. placebo or miglitol groups). Diarrhea (or soft stools) and flatulence were more common in both miglitol groups than in the other two groups in a dose-dependent manner, but resulted in relatively few study dropouts. Treatment with miglitol offers the elderly type 2 diabetic patient significant reductions in daylong glycemia as measured by HbA1c. The greater HbA1c reductions seen with once-a-day glyburide occurred at a cost of significant increases in weight, insulin levels, and the incidences of clinical and subclinical hypoglycemia, which did not occur in the miglitol groups. alpha-glucosidase inhibitors are a useful and relatively safe therapeutic option in the elderly patient with type 2 diabetes.
Johnston
P S
PS
Bayer Pharmaceuticals, West Haven, Connecticut 06516, USA.
Lebovitz
H E
HE
Coniff
R F
RF
Simonson
D C
DC
Raskin
P
P
Munera
C L
CL
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005215:Fasting; D005260:Female; D005502:Food; D005944:Glucosamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005905:Glyburide / Q000009:adverse effects / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050112:Imino Pyranoses; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male
D017485:1-Deoxynojirimycin; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D005944:Glucosamine; D005905:Glyburide; D006442:Glycated Hemoglobin; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D050112:Imino Pyranoses; D007328:Insulin; C045621:miglitol