Advantages of α-Glucosidase Inhibition as Monotherapy in Elderly Type 2 Diabetic Patients

• Published in: The journal of clinical endocrinology and metabolism 1998-05, Vol.83 (5), p.1515-1522
• Main Authors: Johnston, Peter S, Lebovitz, Harold E, Coniff, Robert F, Simonson, Donald C, Raskin, Philip, Munera, Catherine L
• Format: Article
• Language: English
• Subjects: 1-Deoxynojirimycin - analogs & derivatives; Aged; Biological and medical sciences; Blood Glucose - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Double-Blind Method; Enzyme Inhibitors - therapeutic use; Fasting; Female; Food; General and cellular metabolism. Vitamins; Glucosamine - adverse effects; Glucosamine - analogs & derivatives; Glucosamine - therapeutic use; Glyburide - adverse effects; Glyburide - therapeutic use; Glycated Hemoglobin A - metabolism; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents - therapeutic use; Imino Pyranoses; Insulin - blood; Kinetics; Male; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jcem.83.5.4824

The objective of this study was to determine the safety, efficacy, and tolerability of the α-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 outpatient 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.α -glucosidase inhibitors are a useful and relatively safe therapeutic option in the elderly patient with type 2 diabetes.