Double-masked, placebo-controlled, dose-ranging study of troglitazone 10 to 200 mg once daily in non—insulin-dependent diabetes mellitus

Troglitazone in combination with sulphonylurea improves glycaemic control in Type 2 diabetic patients inadequately controlled by sulphonylurea therapy alone

“…Other effects of troglitazone, which demonstrate the distinction between insulin action enhancer and insulin stimulating agent, are also seen in this study. An enhanced insulin action could be responsible for reductions in insulin (13% with troglitazone 200 mg compared with sulphonylurea alone), which were of a similar magnitude to those recorded in monotherapy studies against placebo (9–10% greater with troglitazone compared with placebo; 5% with troglitazone 100 mg (not significant))[3, 4].…”

“…Although this study was not designed to demonstrate a synergistic effect, troglitazone, in combination with a sulphonylurea, exerted glucose‐lowering effects of a similar magnitude to those observed when troglitazone is used alone[4]. As in previous studies, the 200 mg dose of troglitazone was more effective in improving glycaemic control than the 100‐mg dose[3, 4, 13]. Other effects of troglitazone, which demonstrate the distinction between insulin action enhancer and insulin stimulating agent, are also seen in this study.…”

“…In monotherapy studies, varied effects of troglitazone on blood lipids have been observed. In two studies with higher doses of troglitazone (up to 800 mg) significant reductions in triglyceride levels and increases in HDL‐cholesterol have been observed[3, 15], however, in a third study with lower doses of troglitazone (up to 200 mg) no such changes were seen[4]. Sulphonylureas have been shown to have no direct effects on lipid metabolism and inconsistent changes in triglyceride and HDL‐cholesterol levels have been reported[12].…”

“…Indeed, a pilot study showed that adding troglitazone 600 mg once daily to glibenclamide significantly reduced postprandial and 24‐h serum glucose levels[13]. In addition, and in line with troglitazone monotherapy studies, significant reductions in serum insulin and proinsulin were observed in the troglitazone combination group compared with the glibenclamide only group[3, 4].…”

“…Troglitazone is a peroxisome proliferator‐activated receptor‐γ (PPARγ) agonist with insulin action enhancing properties. Placebo‐controlled studies have shown that, as monotherapy at doses of 200–600 mg daily, troglitazone improves glycaemic control, reduces hyperinsulinaemia and has beneficial effects on the lipid parameters in patients with Type 2 DM not controlled by diet alone[3, 4]. Two recent studies have shown that troglitazone is also effective in combination with insulin[5] or metformin[6].…”