[Therapy with glitazones--a risk for cardiovascular disease?].
BACKGROUND
Thiazolidinediones significantly reduce fasting plasma glucose and HbA (1c). These effects are due to improved insulin sensitivity by activating the nuclear PPAR-gamma (peroxisomal proliferator-activated receptors-gamma) and affection of different intracellular functions. The objective of this review was to analyse recently published studies and meta-analyses about thiazolidinediones, which suggested a significant cardiovascular risk associated with rosiglitazone therapy. Therefore clinicians have been left uncertain as to whether rosiglitazone should still be considered for the treatment of type-2-diabetes.


CONCLUSIONS
An important side-effect of thiazolidinediones is fluid retention and edema. Therefore, heart failure NYHA I-IV is a contraindication for treatment with Thiazolidinediones. Pioglitazone shows favourable changes in lipid parameters like decrease of serum-triglycerides and increase of HDL-cholesterol, while Rosiglitazone temporarily increases LDL-cholesterol. In patients with type-2-diabetes mellitus and a high cardiovascular risk the PROactive study did not show a significant effect on the primary endpoint but significantly reduced the predefined secondary combined endpoint of total mortality, nonfatal myocardial infarction and stroke. Conversely, recently published meta-analyses suggested an increased cardiovascular risk and myocardial infarction rate associated with rosiglitazone therapy.


CONCLUSIONS
Treatment with Rosiglitazone should be reconsidered because of a potential cardiovascular risk. In high risk patients without heart failure pioglitazone may be favoured for treatment of type 2 diabetes mellitus.
Klinik III für Innere Medizin, Universitätsklinikum Köln, Köln.
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Rottlaender
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Michels
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Erdmann
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Hoppe
D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D000075202:Contraindications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007333:Insulin Resistance; D000077205:Pioglitazone; D018570:Risk Assessment; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use
D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones