Troglitazone has no effect on red cell mass or other erythropoietic parameters.
OBJECTIVE
Troglitazone is a new anti-diabetic agent for the treatment of type 2 diabetes. In placebo-controlled trials troglitazone improves glycaemic control, reduces hyperinsulinaemia and has beneficial effects on blood lipids. However, minor, reversible reductions in erythrocyte count, haemoglobin and haematocrit with no associated clinical symptoms have been observed in some troglitazone-treated patients. The primary objective of the present study was to determine if these changes could be explained by a decrease in red cell mass or change in plasma volume.


METHODS
Twenty-four healthy males were randomized in a double-blind manner to troglitazone (200 or 600 mg per day) or placebo for 6 weeks. Blood samples for the measurement of red cell mass and plasma volume were obtained in the 2 weeks prior to treatment and after 6 weeks of treatment. Reticulocyte and erythrocyte counts, haemoglobin and haematocrit were also measured.


RESULTS
At the end of the treatment period there were no statistically significant changes in red cell mass. Similarly there were no changes in reticulocyte count, erythropoietin or soluble transferrin receptors. These data indicate that troglitazone does not affect erythropoiesis. In addition, troglitazone was not associated with increased red blood cell destruction or haemolysis. There was a trend towards increased plasma volume in the troglitazone groups: increases of 2.5 ml x kg(-1) (5.7% increase) in the troglitazone 200 mg group and 3.4 ml x kg(-1) (7.8% increase) in the troglitazone 600 mg group were observed compared with placebo.


CONCLUSIONS
These data suggest that dilutional effects related to a modest increase in plasma volume may explain the haematological changes seen in other clinical trials with high doses of troglitazone, although this study has shown that the changes in plasma volume are not statistically significant.
Young
M M
MM
International Product Safety and Pharmacovigilance, Glaxo Wellcome Research & Development Ltd., Greenford, Middlesex, UK.
Squassante
L
L
Wemer
J
J
van Marle
S P
SP
Dogterom
P
P
Jonkman
J H
JH
D000328:Adult; D002839:Chromans / Q000494:pharmacology*; D004311:Double-Blind Method; D004906:Erythrocyte Count / Q000187:drug effects; D004909:Erythrocyte Indices / Q000187:drug effects; D004911:Erythrocyte Volume / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects*; D006400:Hematocrit; D006454:Hemoglobins / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D012156:Reticulocytes / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D006454:Hemoglobins; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone