Endocrine Abstracts

Accumulating facts show that incretin-modulating therapy could be beneficial in both glycemic control and nephroprotection in type 2 diabetes (DM2). Clinical evidence for nephroprotective potential of DPP-4 inhibitors is limited and predictive determinants are unknown. The study conducted with DM2 patients aimed to assess renal effects of vildagliptin addition and identify their clinical and laboratory predictors. The study enrolled 44 insulin-treated male and female type 2 diabetic patients, aged 49–70 years with satisfactory glycemic and blood pressure (BP) control, without overt chronic kidney disease, severe micro- and macrovascular diabetic complications, and non-diabetic renal impairment. Patients were randomized either to continue insulin therapy (control, n=21), or to receive vildagliptin (50 mg/daily) added-on insulin therapy (Vgroup, n=23). At baseline and after 6 months of treatment we assessed eGFR using serum creatinine (eGFRcr), cystatin C (eGFRcys), and both (eGFRcr-cys), and creatinine-adjusted urinary markers (albuminuria (UACR), and collagen type IV (uColIV). Groups were comparable on the basis of sex and age. A2 category of CKD was detected in 47.6% of control patients and in 52.2% – in Vgroup, P=0.76. At baseline there were no significant differences in assessed parameters. In the control group none of them changed significantly after 6 months of the treatment. Patients from Vgroup demonstrated significant decrease in HbA1c, insulin requirement along with the frequency of hypoglycemic episodes. Significant reduction in diastolic BP, serum cystatin C and excretion of uColIV was documented in Vgroup as well as the increase of eGFRcys and eGFRcr-cys. Correlation analysis showed that neither changes of serum cystatin C, eGFRcys and eGFRcr-cys nor changes of uColIV in Vgroup were significantly related to the dynamics of HbA1c (r=−0.31, 0.21, 0.19, and 0.13, respectively, P>0.05 each). We found inverse association between the changes of systolic BP and eGFRcr-cys (β=−0.47, R²=0.22, R²=0.02) suggesting that hemodynamic mechanisms at least partially contribute to vildagliptin renal action. Stepwise regression analysis showed that lower levels of baseline eGFRcys were independent predictors of both eGFRcys and eGFRcr-cys increase (β=−0.61, R²=0.37, and β=−0.45, R²=0.20, respectively, P<0.05 each). Reduction of uColIV excretion was more pronounced in older patients (β=−0.74) with lower levels of diastolic BP (β=0.57), R²=0.46, P=0.002. In conclusion, vildagliptin administration was associated with reduction of uColIV excretion along with the increase of eGFRcreat-cys and eGFRcys, independent of glycemic control. Older age and lower baseline values of diastolic BP were predictive of better uColIV-response in patients receiving vildagliptin.