EFFECTS OF THE CARBOHYDRASE INHIBITOR MIGLITOL IN SULFONYLUREA-TREATED NIDDM PATIENTS

OBJECTIVE- To examine the effects of the carbohydrase inhibitor miglit ol (BAY m 1099) on the metabolic profiles of non-insulin-dependent dia betes mellitus (NIDDM) patients suboptimally controlled on maximal dai ly doses of sulfonylurea (SFU) agents. RESEARCH DESIGN AND METHODS- Mu lticenter, double-blind, randomized, placebo-controlled 14-week clinic al trial with six-week, single-blind placebo lead-in and run-out perio ds. NIDDM volunteers (192) with fasting plasma glucose (FPG) 140-250 m g/dl and hemoglobin A(1c) (HbA(1c)) 6.5-12.0% after at least 4 weeks o f treatment with SFU at maximal dose were stratified by baseline HbA(1 c) (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 mig litol 3 times a day (n = 68). Efficacy was assessed by HbA(1c), FPG, i nsulin, and lipid concentrations, and by plasma glucose and serum insu lin responses to a standard meal. RESULTS- In the 50 and 100 mg miglit ol treatment groups, the mean changes from baseline in HbA(1c) (with p lacebo 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 miglito l dose compared with placebo (P = 0.0001 for each), with associated re ductions in integrated serum insulin response (P < 0.05). No significa nt drug-associated changes in FPG, insulin, or cholesterol levels were noted, but fasting triglyceride levels were lowered significantly wit h the 50 mg miglitol dose. Miglitol's side effects were limited to fla tulence, loose stools, and abdominal discomfort, which were dose-relat ed, rapidly resolved on drug discontinuation, and led to withdrawal fr om the study of 5 and 15% of patients taking 50 and 100 mg miglitol, r espectively. CONCLUSIONS- Miglitol may be indicated as effective adjuv ant therapy in NIDDM patients with suboptimal metabolic control despit e 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 migl itol 3 times a day because of comparable efficacy and substantially re duced side effects.