Effect of troglitazone in insulin-treated patients with type II diabetes mellitus. Troglitazone and Exogenous Insulin Study Group

N Engl J Med. 1998 Mar 26;338(13):861-6. doi: 10.1056/NEJM199803263381302.

Abstract

Background: Troglitazone is a new oral antidiabetic drug that increases the sensitivity of peripheral tissues to insulin. It may therefore increase the efficacy of exogenous insulin in patients with insulin-resistant diabetes mellitus.

Methods: We studied the effect of troglitazone or placebo in 350 patients with poorly controlled non-insulin-dependent (type 2) diabetes mellitus (glycosylated hemoglobin values, 8 to 12 percent; normal, 4.3 to 6.1 percent) despite therapy with at least 30 U of insulin daily. The patients were randomly assigned to receive 200 mg of troglitazone (116 patients), 600 mg of troglitazone (116 patients), or placebo (118 patients) daily for 26 weeks. Insulin doses were not increased and were reduced only to prevent hypoglycemia. Glycosylated hemoglobin, serum glucose while fasting, serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured 5 times during an 8-week base-line period and 10 times during the 26-week treatment period. Daily insulin doses were recorded during both periods.

Results: Ninety percent of the patients completed the study. The adjusted mean glycosylated hemoglobin values decreased by 0.8 and 1.4 percentage points, respectively, in the group given 200 mg of troglitazone and the group given 600 mg of troglitazone, and fasting serum glucose concentrations decreased by 35 and 49 mg per deciliter (1.9 and 2.7 mmol per liter), respectively, despite decreases in the insulin dose of 11 percent and 29 percent (P<0.001 for all comparisons with the placebo group). Serum total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations increased slightly and serum triglyceride concentrations decreased slightly in the troglitazone-treated patients.

Conclusions: When given in conjunction with insulin, troglitazone improves glycemic control in patients with type 2 diabetes mellitus.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Blood Glucose / analysis
  • Cholesterol / blood
  • Chromans / adverse effects
  • Chromans / pharmacology
  • Chromans / therapeutic use*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Male
  • Middle Aged
  • Thiazoles / adverse effects
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*
  • Thiazolidinediones*
  • Triglycerides / blood
  • Troglitazone

Substances

  • Blood Glucose
  • Chromans
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Thiazoles
  • Thiazolidinediones
  • Triglycerides
  • Cholesterol
  • Troglitazone