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

Abstract

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_1c) 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 < 1 kg. Dipeptidyl peptidase–4 inhibitors may be used as monotherapy in patients with CKD and HbA_1c 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_1c levels < 9%, but studies are needed to evaluate these combinations in patients with renal insufficiency. Long–term 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.

Keywords:

• DPP-4 inhibitors
• type 2 diabetes mellitus
• chronic kidney disease
• renal insufficiency
• safety