Monotherapy with sulfonylurea may result in the exhaustion of pancreatic beta-cell function, fat accumulation, and
dyslipidemia. We examined the possibility of
dose reduction by administering sulfonylurea together with
troglitazone, and investigated changes in insulin secretion and fat deposition. Seventy-eight patients with
type 2 diabetes adequately controlled with
glibenclamide were randomly allocated to a
troglitazone (400 mg/d)-added group (n = 40) or a control group without placebo (n = 38) and monitored for 24 weeks. The daily dose of
glibenclamide was adjusted to maintain stable HbA(1c) levels. Fat accumulation to the liver and thigh muscle were measured in mean Hounsfield units determined on computed tomography (CT) scan. Visceral fat accumulation (V), subcutaneous fat accumulation (S), and the V/S ratio were also determined by CT scan. The daily dose of
glibenclamide and serum fasting
insulin level in the
troglitazone-added group significantly decreased (from 4.05 +/- 2.50 mg/d to 1.84 +/- 1.65 mg/d and from 8.47 +/- 4.62 microU/mL to 6.49 +/- 3.28 microU/mL, respectively) during the observation period compared with the control group (P < .01 and P < .01, respectively). Serum
triglyceride and homeostasis model
insulin resistance index (HOMA-R) in the
troglitazone-added group decreased significantly in comparison to the control group (P < .05 and P < .01, respectively). The mean Hounsfield units of liver significantly decreased in the control group compared with the
troglitazone-added group (P < .05). Visceral fat area and the V/S ratio significantly increased in the control group compared with the
troglitazone-added group (P < .01 and P < .01, respectively).
Glibenclamide monotherapy resulted in fat accumulation accompanied by
dyslipidemia. An alternate conclusion is that
troglitazone reversed
type 2 diabetes (not sulfonylurea)-associated fat accumulation. The addition of
troglitazone decreased daily doses of
glibenclamide, preserved fasting insulin secretion, improved fat accumulation in liver, and prevented
dyslipidemia.