Anemia due to coadministration of renin-angiotensin-system inhibitors and PPARγ agonists in uncomplicated diabetic patients.

Therapy with either angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) or thiazolidinediones (TZD) is associated with dose-dependent decrements in hematocrit and hemoglobin levels. We aimed to investigate the impact of the coadministration of TZD and ACEI/ARB on hematocrit and hemoglobin values in uncomplicated patients with type 2 diabetes mellitus and normal serum creatinine.Data from patients with type 2 diabetes currently followed, were reviewed and patients treated with ACEI/ARB and/or TZD were identified. For the purpose of this study the following 4 groups of 30 stable non-anemic diabetic patients each matched for age, gender, and BMI were formed. Group ACEI/ARB included patients on ACEI/ARB without TZD, group TZD included patients on TZD and antihypertensive agents other than ACEI/ARB, group ACEI/ARB/TZD consisted of patients on combined therapy with ACEI/ARB and TZD and the control group C included patients never exposed to ACEI/ARB or TZD. Clinical and laboratory data were collected prior to initiation of treatment and after 6 months.Neither hematocrit nor hemoglobin showed any significant change from baseline at the end of the study in group C. In both group ACEI/ARB and group TZD a small, but statistically significant reduction in hematocrit (~ 1% point) and hemoglobin levels (~ 0.3 g/dl) was seen. A greater statistically and clinically important reduction in hematocrit (~ 3% points) and hemoglobin (~ 1 g/dl) levels was observed in group ACEI/ARB/TZD. Furthermore, incident anemia at the end reached 7% in group TZD and 23% in group ACEI/ARB/TZD.Coadministration of RAS inhibitors and PPAR-γ agonists should be considered in the differential diagnosis of hematocrit lowering and anemia in uncomplicated type 2 diabetic patients with normal serum creatinine. Further studies are required to clarify the mechanism(s), the cardiovascular consequences and the cost utility of anemia workup in such patients.