Effects of the carbohydrase inhibitor miglitol in sulfonylurea-treated NIDDM patients.
OBJECTIVE
To examine the effects of the carbohydrase inhibitor miglitol (BAY m 1099) on the metabolic profiles of non-insulin-dependent diabetes mellitus (NIDDM) patients suboptimally controlled on maximal daily doses of sulfonylurea (SFU) agents.


METHODS
Multicenter, double-blind, randomized, placebo-controlled 14-week clinical trial with six-week, single-blind placebo lead-in and run-out periods. NIDDM volunteers (192) with fasting plasma glucose (FPG) 140-250 mg/dl and hemoglobin A1c (HbA1c) 6.5-12.0% after at least 4 weeks of treatment with SFU at maximal dose were stratified by baseline HbA1c (above and below 9.0%) and then randomly assigned within strata to placebo (n = 63), 50 mg miglitol 3 times a day (n = 61), or 100 mg miglitol 3 times a day (n = 68). Efficacy was assessed by HbA1c, FPG, insulin, and lipid concentrations, and by plasma glucose and serum insulin responses to a standard meal.


RESULTS
In the 50 and 100 mg miglitol treatment groups, the mean changes from baseline in HbA1c (with placebo values subtracted) were 0.82 and 0.74%, respectively, and were highly significant (P = 0.0001 in each case). Mean peak plasma glucose levels after a standard test meal were comparably lowered by 57 mg/dl with the 50 mg miglitol dose, and by 64 mg/dl with the 100 mg miglitol dose compared with placebo (P = 0.0001 for each), with associated reductions in integrated serum insulin response (P < 0.05). No significant drug-associated changes in FPG, insulin, or cholesterol levels were noted, but fasting triglyceride levels were lowered significantly with the 50 mg miglitol dose. Miglitol's side effects were limited to flatulence, loose stools, and abdominal discomfort, which were dose-related, rapidly resolved on drug discontinuation, and led to withdrawal from the study of 5 and 15% of patients taking 50 and 100 mg miglitol, respectively.


CONCLUSIONS
Miglitol may be indicated as effective adjuvant therapy in NIDDM patients with suboptimal metabolic control despite conventional treatment with diet and maximal daily doses of SFU. The dose of 50 mg miglitol 3 times a day may be preferable to 100 mg miglitol 3 times a day because of comparable efficacy and substantially reduced side effects.
Johnston
P S
PS
Miles Inc. Pharmaceutical Division, West Haven, Connecticut 06516.
Coniff
R F
RF
Hoogwerf
B J
BJ
Santiago
J V
JV
Pi-Sunyer
F X
FX
Krol
A
A
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005944:Glucosamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D050112:Imino Pyranoses; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D017485:1-Deoxynojirimycin; D015415:Biomarkers; D001786:Blood Glucose; D005944:Glucosamine; D006442:Glycated Hemoglobin; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D050112:Imino Pyranoses; D007328:Insulin; D008055:Lipids; C045621:miglitol