Rosiglitazone in the treatment of type 2 diabetes mellitus: a critical review

Clin Ther. 2000 Oct;22(10):1151-68; discussion 1149-50. doi: 10.1016/s0149-2918(00)83060-x.


Objective: This article reviews the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosing of rosiglitazone, the second thiazolidinedione approved for the treatment of type 2 diabetes mellitus.

Methods: Background information for this article was obtained from searches of MEDLINE , Iowa Drug Information Service, and International Pharmaceutical Abstracts, as well as from data on file with the manufacturer of rosiglitazone.

Results: Rosiglitazone is indicated for use alone or in combination with metformin or sulfonylureas for the maintenance of glycemic control in patients with type 2 diabetes mellitus. Rather than stimulation of insulin secretion, rosiglitazone's primary mechanism of action is sensitization of tissues to insulin through activation of the peroxisome proliferator-activated receptor gamma and increasing expression of the glucose transporter-4 receptor. Rosiglitazone is administered orally, is absorbed almost completely, and is 99.8% bound to plasma proteins. The majority of a dose is metabolized by the cytochrome P-450 2C8 isozyme, with the inactive metabolites excreted primarily in the urine. Four to 8 mg/d of rosiglitazone given alone or in combination with metformin, sulfonylureas, or insulin has produced reductions in baseline fasting plasma glucose and glycosylated hemoglobin in studies of up to 1 year's duration. Common adverse effects (occurring in > or = 5.0% of patients) include upper respiratory tract infection, injury, and headache. Edema, weight gain, and increased low-density lipoprotein cholesterol concentrations have also been observed. It is recommended that rosiglitazone be avoided in patients with alanine aminotransferase levels >2.5 times normal. No clinically relevant drug interactions have been documented with rosiglitazone to date. The initial starting daily dose of rosiglitazone is 4 mg in single or divided doses, without regard to meals, to a maximum of 8 mg.

Conclusions: No direct comparative trials of the efficacy and safety of rosiglitazone versus those of the other available thiazolidinedione, pioglitazone, have yet been performed. The role of rosiglitazone as a single agent and in combination with other antidiabetic agents remains to be clarified as additional comparative and long-term data become available.

Publication types

  • Review

MeSH terms

  • Aged
  • Area Under Curve
  • Biological Availability
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Interactions
  • Drug Therapy, Combination
  • Humans
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / blood
  • Hypoglycemic Agents* / pharmacokinetics
  • Hypoglycemic Agents* / therapeutic use
  • Insulin / therapeutic use
  • Metformin / therapeutic use
  • Middle Aged
  • Rosiglitazone
  • Thiazoles* / adverse effects
  • Thiazoles* / blood
  • Thiazoles* / pharmacokinetics
  • Thiazoles* / therapeutic use
  • Thiazolidinediones*


  • Hypoglycemic Agents
  • Insulin
  • Thiazoles
  • Thiazolidinediones
  • Rosiglitazone
  • Metformin