Troglitazone prevents the rise in visceral adiposity and improves fatty liver associated with sulfonylurea therapy--a randomized controlled trial.
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.
Katoh
S
S
Jikei University School of Medicine, Tokyo, Japan.
Hata
S
S
Matsushima
M
M
Ikemoto
S
S
Inoue
Y
Y
Yokoyama
J
J
Tajima
N
N
D000273:Adipose Tissue / Q000187:drug effects / Q000254:growth & development; D000368:Aged; D002839:Chromans / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000097:blood / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity; D010865:Pilot Projects; D013453:Sulfonylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone