Use of Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease

Choices of antidiabetic agents for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) are limited. Available data suggest that the use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be safe in patients at various stages of renal insufficiency. However, except for linagliptin, dosage adjustment is necessary. The efficacy of DPP-4 inhibitors in patients with renal insufficiency is generally similar to that of the general population with T2DM, with reductions in mean glycated hemoglobin (HbA(lc)) levels of 0.7% to 1.0% compared with baseline, and 0.4% to 0.7% compared with placebo. The frequency of moderate hypoglycemia is 21% to 80% higher with DPP-4 inhibitors compared with placebo, but the frequency of severe hypoglycemia is similar to that with placebo. The use of DPP-4 inhibitors in patients with renal insufficiency is associated with a slight weight loss of < I kg. Dipeptidyl peptidase-4 inhibitors may be used as monotherapy in patients with CKD and HbA(lc) levels < 8.5% as an alternative to insulin, glipizide, or pioglitazone. They can also be used as add-on therapy to glipizide and/or pioglitazone in patients with HbA(lc) levels < 9%, but studies are needed to evaluate these combinations in patients with renal insufficiency. Longterm and large-scale clinical trials are underway to better determine the safety and efficacy of DPP-4 inhibitors in patients with T2DM with and without CKD.