MULTICENTER, PLACEBO-CONTROLLED TRIAL COMPARING ACARBOSE (BAY G-5421)WITH PLACEBO, TOLBUTAMIDE, AND TOLBUTAMIDE-PLUS-ACARBOSE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

BACKGROUND: Acarbose delays release of glucose from complex carbohydra tes and disaccharides by inhibiting intestinal alpha-glucosidases, the reby attenuating postprandial increments in blood glucose and insulin. This multicenter, double-blind, placebo-controlled study compared the efficacy and safety of diet alone, acarbose, tolbutamide, and acarbos e-plus-tolbutamide in non-insulin-dependent diabetes mellitus (NIDDM) patients. PATIENTS AND METHODS: A total Of 290 patients with NIDDM and fasting plasma glucose levels of at least 140 mg/dL were randomized t o receive treatment TID with acarbose 200 mg, tolbutamide 250 to 1,000 mg, a combination of both drugs, or placebo. A 6-week run-in period w as followed by double-blind treatment for 24 weeks, then a 6-week foll ow-up period. RESULTS: Ail active treatments were superior (P <0.05) t o placebo in reducing postprandial hyperglycemia and HbA(1c) levels. T he ranking in order of efficacy was: acarbose-plus-tolbutamide, tolbut amide, acarbose, and placebo. The postprandial reductions in glucose w ere approximately 85 mg/dL for acarbose-plus-tolbutamide, 71 mg/dL for tolbutamide, 56 mg/dL for acarbose, and 13 mg/dL for placebo. Tolbuta mide was associated with increases in body weight and postprandial ins ulin levels when taken alone, but these were ameliorated when tolbutam ide was taken in combination with acarbose. Acarbose alone or in combi nation with tolbutamide caused significantly more gastrointestinal adv erse events (mainly flatulence and soft stools or diarrhea) than tolbu tamide or placebo, but these were generally well tolerated. Clinically significant elevations in hepatic transaminase levels occurred in 3 p atients in the acarbose group and 2 in the acarbose-plus-tolbutamide g roup. Transaminase levels returned to normal when therapy was disconti nued. CONCLUSIONS: Acarbose was effective and well tolerated in the tr eatment of NIDDM. Control of glycemia was significantly better with ac arbose compared with diet alone. Acarbose-plus-tolbutamide was superio r to tolbutamide alone.