Tuttle KR et al. (2005) The effect of ruboxistaurin on nephropathy in type 2 diabetes. Diabetes Care 28: 2686–2690

Approximately 40% of patients with diabetes develop nephropathy, which often leads to end-stage renal disease. Current treatment strategies—use of antihypertensives, glycemic control, and limiting dietary protein—are inadequate in many patients. A recent randomized, controlled, double-blind pilot study shows that ruboxistaurin might be beneficial in diabetic nephropathy.

From June 2002 to May 2003, 123 patients with type 2 diabetes and persistent albuminuria (albumin : creatinine ratio [ACR] 200–2,000 mg/g) were randomized to either ruboxistaurin (32 mg/day) or placebo, for 1 year. Patients continued antihypertensive treatment (renin–angiotensin system inhibition) throughout. Follow-up visits at months 1, 3, 6 and 12 recorded urinary ACR, blood pressure, and adverse events. The primary endpoint was a reduction in urinary ACR; estimated glomerular filtration rate (eGFR) was also calculated.

Baseline urinary ACR values and eGFR were similar in the two groups. Patients receiving ruboxistaurin experienced a significant ACR decrease after 1 year (−24 ± 9%; P = 0.020), and eGFR did not decrease significantly. By contrast, ACR did not decrease significantly in placebo patients (−9 ± 11%; P = 0.430), and eGFR showed a significant decline (P = 0.009). ACR reduction and eGFR changes did not show significant differences between treatment groups, but the study was not adequately powered to determine such differences.

Despite various study limitations, the authors conclude that ruboxistaurin shows promising beneficial effects on albuminuria and renal function in diabetic nephropathy, and state that this treatment might be beneficial when given in combination with standard therapies. This pilot study indicates the need for a larger, sufficiently powered trial of ruboxistaurin, with longer follow-up.