Cilostazol effectively attenuates deterioration of albuminuria in patients with type 2 diabetes: a randomized, placebo-controlled trial

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Cilostazol is an antiplatelet, antithrombotic agent with anti-inflammatory properties. To date, no clinical study has specifically evaluated the efficacy of cilostazol in patients with diabetic nephropathy (DN). We hypothesized that cilostazol might delay renal deterioration in DN patients at high risk of progression. Between April 2008 and April 2010, we screened 156 consecutive patients aged 35–80 years who were first diagnosed with type 2 diabetes after the age of 30 years. Of these, 90 patients with DN, as defined by morning spot urine microalbuminuria (MAU) >20 mg/L or an albumin-to-creatinine ratio (ACR) >30 μg/mg on at least two consecutive occasions within the prior 3 months, were enrolled into a 52-week randomized, single-blinded, placebo-controlled trial of oral cilostazol 100 mg twice daily or placebo (45 subjects in each group). Morning spot urine samples were collected to determine MAU and ACR. Fasting plasma levels of metabolic, endothelial variables, and inflammatory markers were examined. Following 52 weeks of treatment, urinary MAU and ACR were significantly reduced in the cilostazol group compared with the placebo group (P = 0.024 and P = 0.02, respectively). In regression analyses, changes in monocyte chemotactic protein-1, E-selectin, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were significantly associated with changes in MAU and ACR. Net changes of E-selectin (P < 0.001) and sVCAM-1 (P < 0.05) were independent predictors of change in MAU and ACR, respectively. Our results suggest that cilostazol may effectively attenuate deterioration of albuminuria in patients with type 2 diabetes. This effect is likely mediated by an improvement of adhesion molecules.

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This work was supported by research grants from the National Science Council (NSC 101-2314-B-016-032) and the Tri-Service General Hospital (TSGH-C97-S04 and TSGH-C102-118) in Taiwan. We declare that all authors listed have actively participated in the study and met the requirements of the authorship. YJH wrote the manuscript, supervised the project, and reviewed/edited the manuscript. FHK, CHL, CHH, and CTH analyzed the data and reviewed/edited the manuscript. FCH and YSS contributed to the discussion and statistical analyses. All authors have read and approved the final version of the manuscript. We are grateful to all participants in this study and Miss Wang for her assistance with laboratory measurement.

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Correspondence to Yi-Jen Hung.

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Tang, W., Lin, F., Lee, C. et al. Cilostazol effectively attenuates deterioration of albuminuria in patients with type 2 diabetes: a randomized, placebo-controlled trial. Endocrine 45, 293–301 (2014) doi:10.1007/s12020-013-0002-3

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  • Adhesion molecules and diabetic nephropathy
  • Cilostazol
  • Microalbuminuria