Effect of sitagliptin on proteinuria in patients with type 2 diabetes A renoprotective effect of sitagliptin

Diabetic nephropathy, the leading cause of chronic renal failure, is related to diabetes poor control. Some antihyperglycemic drugs like dipeptidyl peptidase‑4 inhibitors have shown to prevent diabetic nephropathy. This study endeavors to assess the effect of sitagliptin on proteinuria in Iranian type 2 diabetics.

A total of 90 type 2 diabetic patients aged between 30 and 80 years with glycated hemoglobin (HbA1C) <8.5 and normotensive under treatment of angiotensin‑converting enzyme inhibitors or angiotensin receptor blockers were randomly assigned into two groups. One group received 50 mg sitagliptin per day and the other group received placebo. The two groups were evaluated for albumin–creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) at baseline and 3 months later.

Eighty‑four patients, 38 (45%) males and 46 (55%) females, were enrolled in this study. The mean age was 58.47 ± 7.33. The two groups did not differ in baseline characteristics. After 3 months, in the sitagliptin group, HbA1C (7.89 ± 0.39 to 7.37 ± 0.61, P < 0.001), fasting blood sugar (FBS) (136.86 ± 22.51 to 130.53, P = 0.04), systolic blood pressure (BP) (124.39 ± 9.70 mmHg to 119.32 ± 9 mmHg), diastolic BP (76.44 ± 6.53 to 73.13 ± 5.34 mmHg, P < 0.001), and ACR (314.40 ± 414.64 to 293.49 ± 400.71, P < 0.001) were significantly decreased and eGFR was significantly increased (73.35 ± 10.73 to 76.86 ± 10.59, P < 0.001) at 3 months compared to the placebo group. ACR reduction was higher in macroalbuminuric (Ma) patients compared to microalbuminuric (Mi) patients in the sitagliptin group (−30.25 ± 35.57 vs. −11.12 ± 14.01, P = 0.02). No significant difference was observed between the Ma and Mi subgroups regarding changes in eGFR. Univariate analysis showed that changes in ACR correlated with FBS (r = 0.68, P < 0.0001), insulin (r = 0.44, P = 0.03), and homeostatic model assessment for insulin resistance (r = 0.69, P < 0.0001) and did not correlate with eGFR and BP.

In conclusion, sitagliptin is a well‑tolerated drug that improves glycemic control, lowers BP, and reduces urinary albumin excretion, especially in Ma type 2 diabetic patients.