The metabolic effects of troglitazone in patients with diabetes and end-stage renal disease.
Thiazolidinediones (TZD) are effective agents for the treatment of hyperglycemia, and appear ideal in diabetic patients with progressive or end-stage renal disease because of its predominant hepatic clearance. Troglitazone, the first available TZD for clinical use, was withdrawn due to safety concerns; however, studies completed with this agent can provide a better understanding of the class effect of TZDs. This study was an open-label, controlled clinical trial examining the safety and efficacy of troglitazone in type 2 diabetic patients with end-stage renal disease (ESRD). Twelve subjects were randomized to parallel study groups and treated for 6 mo with or without troglita-zone at a maximum dose of 600 mg/d in addition to continuing their previous diabetes medications (insulin or sulfonylurea). The results showed no significant differences in glycemic control with or without troglit-azone treatment for 6 mo. However, there was a significant reduction in insulin dosage with troglitazone treatment (22.9 +/- 7.3 units/d) than without troglita-zone treatment (54 +/- 12.9 units/d) (p < 0.05), as well as the change in the insulin dosage from baseline between the two groups (troglitazone, -8.4 units vs control, +4.3 units, p < 0.05). Weight changes and aspartate amino-transferase levels greater than 1.5 times the upper limit of normal were not observed in participants of either treatment group. This study demonstrates that troglit-azone was safe and effective for the treatment of hyper-glycemia in patients requiring dialysis, and strongly supports the clinical use of currently available TZDs in diabetic patients with renal failure.
Mohideen
Pharis
P
Department of Medicine of the John A. Burns School of Medicine, University of Hawaii-Manoa, Honolulu, USA.
Bornemann
Michael
M
Sugihara
Jared
J
Genadio
Viola
V
Sugihara
Valerie
V
Arakaki
Richard
R
D001786:Blood Glucose / Q000187:drug effects; D002839:Chromans / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006441:Hemoglobin A / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage; D007676:Kidney Failure, Chronic / Q000150:complications*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D045162:Thiazolidinediones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D006441:Hemoglobin A; D000077288:Troglitazone