Effects of Alogliptin in Chronic Kidney Disease Patients with Type 2 Diabetes

Abstract

Objective Diabetes is a major risk factor for chronic kidney disease (CKD). In this study, we examined the effects of alogliptin on blood glucose control and the renal function in type 2 diabetes CKD patients. Methods We recruited 36 CKD patients with type 2 diabetes. The patients were followed up for six months after adding alogliptin. Blood biochemical, urine test and office BP values were obtained six months before and after the start of treatment. Results The mean HbA1c value was not decreased; however, the 1,5-AG values tended to improve (p= 0.1023). The mean eGFR was unchanged. There were no significant changes in the patients with an eGFR of 60 mL/min/1.73 m 2 or more (25 patients) or in the patients with an eGFR less than 60 mL/min/1.73 m 2 (11 patients). A total of 15 patients were identified to have rapidly declining diabetic nephropathy, with an annual reduction in eGFR of 5 mL/min/1.73 m 2 or more. The slope of the regression line for eGFR (-1.296 before starting treatment with alogliptin) was positive, increasing up to 0.08786. The eGFR values appeared to stop decreasing and positively reversed. The urinary albumin-to-creatinine ratio exhibited a downward trend. The effect on the renal function was independent of the levels of blood sugar, blood pressure and lipids. Conclusion We examined the ability of alogliptin to maintain the renal function in patients with CKD complicated by type 2 diabetes. Our study suggests that alogliptin can be safely administered in patients with CKD. However, although we expected alogliptin to demonstrate renal protective effects, were unable to detect statistically significant differences. One reason for this finding is that there are few registered cases.

The use of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes & chronic kidney disease

“…The four DPP-4 inhibitors currently approved for the treatment of T2DM in the United States include sitagliptin, saxagliptin, linagliptin, and alogliptin 33-49. These agents are effective at lowering HbA1C in patients age 60 and older with a long duration of T2DM (more than 10 years) and with moderate-to-severe kidney insufficiency, including ESRD and dialysis, while displaying a low propensity for hypoglycemia and weight neutrality 50,51…”

Renal safety of newer medications

“…Data on alogliptin use in renal impairment are not robust due to small numbers; however, plasma concentrations of the medication increase at various stages of renal impairment hence the need to down titrate the dosing based on renal function (see Table ). A small study by Sakai et al . assessed the effects of alogliptin in 36 patients with CKD (defined as eGFR <60 ml/min/1.73 m 2 or microalbuminuria >30 mg/gCr) at six months and, despite not noticing any improvement in HbA 1c , found no change in GFR, with a possible improvement in urinary ACR (not statistically significant).…”

Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes

“…A small, 6-month, open-label study in T2DM patients with CKD reported safe use of alogliptin but no detectable favourable effects on renal function [70]. In patients with CKD caused by immunological abnormalities and treated with steroids, alogliptin improved steroid-induced hyperglycaemia by decrease of glucagon levels through an increase in plasma GLP-1 levels [71].…”