TROGLITAZONE IN COMBINATION WITH SULFONYLUREA RESTORES GLYCEMIC CONTROL IN PATIENTS WITH TYPE-2 DIABETES

OBJECTIVE - To determine if the combination of troglitazone (a peroxis ome proliferator-activated receptor-gamma activator) and sulfonylurea will provide efficacy not attainable by either medication alone. RESEA RCH DESIGN AND METHODS - There were 552 patients inadequately controll ed on maximum doses of sulfonylurea who participated in a 52-week rand omized active-controlled multicenter study. Patients were randomized t o micronized glyburide 12 mg q.d. (G12); troglitazone monotherapy 200, 400, or 600 mg q.d. (T200, T400, T600); or combined troglitazone and glyburide q.d. (T200/G12, T400/G12, T600/G12). Efficacy measures inclu ded HbA(1c), fasting serum glucose (FSG), insulin, and C-peptide. Effe cts on lipids and safety were also assessed. RESULTS - Patients on T60 0/G12 had significantly lower mean (+/- SEM) FSG (9.3 +/- 0.4 mmol/l; 167.4 +/- 6.6 mg/dl) compared with control subjects (13.7 +/- 0.4 mmol /l; 246.5 +/- 6.8 mg/dl; P < 0.0001) and significantly lower mean HbA( 1c) (7.79 +/- 0.2 vs. 10.58 +/- 0.18%, P < 0.0001). Significant dose-r elated decreases were also seen with T200/G12 and T400/G12. Among pati ents on T600/G12, 60% achieved HbA(1c) less than or equal to 8%, 42% a chieved HbA(1c) less than or equal to 7%, and 40% achieved FSG less th an or equal to 7.8 mmol/l (140 mg/dl). Easting insulin and C-peptide d ecreased with all treatments. Overall, triglycerides and free fatty ac ids decreased, whereas HDL cholesterol increased. LDL cholesterol incr eased slightly, with no change in apolipoprotein B. Adverse events wer e similar across treatments. Hypoglycemia occurred in 3% of T600/G12 p atients compared with <1% on G12 or troglitazone monotherapy. CONCLUSI ONS - Patients with type 2 diabetes inadequately controlled on sulfony lurea can be effectively managed with a combination of troglitazone an d sulfonylurea that is safe, well tolerated, and represents a new appr oach to achieving the glycemic targets recommended by the American Dia betes Association.