Peripheral edema, mild weight gain, and anemia are often observed in type II diabetic patients treated with thiazolidinediones (TZDs). Small decreases in hemoglobin (Hb) and hematocrit (Hct) appear to be a class effect of TZDs and are generally attributed to fluid retention, although experimental data are lacking. We analyzed 50 patients with type II diabetes mellitus undergoing either placebo or pioglitazone (PIO, 45 mg/day) for 16 weeks. Before and after therapy, we measured Hb/Hct and used ³H₂O and bioimpedance to quantitate total body water (TBW), extracellular water, and fat‐free mass. The majority (89%) of the increment in body weight was accounted for by increased body fat. Hb and Hct fell significantly in the PIO group (−0.9±0.2 g/dl, −2.4±0.5%, both P<0.0001), without change in TBW. A decline in white blood cell (−0.8±0.1 × 10³/mm³, P<0.0001) and platelet (−15±6 × 10³/mm³, P<0.02) counts was seen after PIO. In conclusion, the small decreases in Hb/Hct observed after 16 weeks of PIO treatment cannot be explained by an increase in TBW. Other causes, such a mild marrow suppressive effect, should be explored.

Clinical Pharmacology & Therapeutics (2007) 82, 275–281; doi:10.1038/sj.clpt.6100146; published online 14 March 2007