The development of dipeptidyl peptidase-IV (DPP-4) inhibitors, such as alogliptin, has led to the improvement in glycemic control in type 2 diabetes (T2D) by preventing the degradation of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. However, the renoprotective effects of alogliptin have not been addressed yet. This 12-week study in Japanese patients with T2D was performed to address the renoprotective effects of alogliptin. In addition, urinary angiotensinogen (AGT), a marker of intrarenal renin-angiotensin system (RAS) activity, was examined to demonstrate the clinical usage as a prognostic marker.
Forty-three patients with T2D (18 women, age: 66.1+/-11.2) were recruited in Miyazaki University and its affiliated hospitals, and alogliptin (25 mg/day) was added on the top of the traditional hypoglycemic agents. The urinary concentrations of albumin (Alb) and AGT were measured using commercially available ELISA kits before and after the alogliptin treatment, and normalized by the urinary concentration of creatinine (Cr) (UAlbCR and UAGTCR, respectively).
The alogliptin treatment tended to decrease UAlbCR (99.6 +/- 26.8 vs. 114.6 +/- 36.0, mg/g Cr). However, this change was not statistically significant (p = 0.1976). Then, we defined good responders to the alogliptin treatment in terms of %change in UAlbCR less than -25% after the 12-week treatment, and a logistic analysis of UAGTCR before the treatment showed the area under the curve (AUC) as 0.644. When we set the cutoff value of UAGTCR as 20.8 μg/g Cr, the maximum specificity (17/27 = 63.0%) and sensitivity (10/16 = 62.5%) were obtained (Youden index = 0.255). Based on this cutoff value of UAGTCR before the treatment, we divided all patients into 2 groups as higher (group H, N = 20) and lower (group L) values of UAGTCR at the baseline. %Change in UAlbCR was significantly lower in the group H compared with the group L (-14.6% +/- 8.6% vs. +22.8% +/- 16.8%, p = 0.0327). These data indicate that the T2D patients with the higher UAGTCR before the treatment would show more decrease in UAlbCR by the alogliptin treatment.
In conclusion, urinary AGT could be a prognostic marker of renoprotective effects of alogliptin in T2D patients.