The thiazolidinediones or "glitazones" a treatment option for type 2 diabetes mellitus.
The glitazones offer a promising alternative to patients not currently able to achieve target gylcemic control with current therapy. Glitazones have a synergistic effect when combined with sulfonlyureas and metformin and may have a favorable effect on the dyslipidemia experienced by patients with type 2 diabetes. The main concern with these agents is safety due to the hepatocellular injury experienced by several patients taking troglitazone. Although elevations in serum alanine amino transferase (ALT) concentrations more than three times normal occurred in 1.9% of patients on troglitazone in clinical trials, liver toxicity was not truly associated with this drug until post-marketing use by more than 600,000 people in the US. The onset of elevated ALT is typically delayed. In the clinical trials only one patient experienced an elevation in the first month, the majority occurred between the third and seventh month. The glitazones should be avoided in patients with liver disease or a history of alcohol abuse. The mechanism of action for troglitazone-induced liver disease is unknown; consequently, identifying a particular subset of people as being at an increased risk for developing liver failure is difficult. Therefore, monitoring liver function is of critical importance. The newer agents rosiglitazone and pioglitazone may provide a safer alternative, however this question will remain unanswered until clinicians have access to substantially more post marketing surveillance data. The two recent cases of hepatocellular injury associated with rosiglitazone therapy further supports a cautious approach to utilization of these agents.
Brown
M N
MN
University of Rhode Island, USA. Brownapc@aol.com
D002839:Chromans / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy*; D004357:Drug Synergism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D000077205:Pioglitazone; D000077154:Rosiglitazone; D013844:Thiazoles / Q000008:administration & dosage*; D045162:Thiazolidinediones; D016896:Treatment Outcome; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077288:Troglitazone; D000077205:Pioglitazone