Safety and efficacy of linagliptin in type 2 diabetes patients with common renal and cardiovascular risk factors

Abstract

Dipeptidyl-peptidase-IV (DPP-4) inhibitors have become an important orally active drug class for the treatment of type 2 diabetes as second-line therapy after metformin failure or as monotherapy or combination therapy with other drugs when metformin is not tolerated or contraindicated. DPP-4 inhibitors act mainly by increasing endogenous incretin hormone concentrations. They stimulate insulin secretion and inhibit glucagon secretion in a glucose-dependent manner with a significantly lower risk for hypoglycaemia than sulfonylureas. Furthermore, DPP-4 inhibitors are weight neutral. Linagliptin is a DPP-4 inhibitor that is eliminated by a hepatobiliary route, whereas the other DPP-4 inhibitors available today show a renal elimination. Therefore, it can be used in normal kidney function as well as in all stages of chronic kidney disease to stage 5 (glomerular filtration rate <15 ml/min/1.73 m2) without dose adjustments. Linagliptin was noninferior to metformin and sulfonylureas in clinical studies. In recent studies, it showed a superior safety profile over sulfonylurea treatment regarding hypoglycaemia and weight gain. More patients reached an HbA1c <7% without hypoglycaemia and weight gain with linagliptin compared with glimepiride. The safety profile with respect to a composite cardiovascular endpoint and stroke was also favourable for linagliptin, most likely due to a higher incidence of hypoglycaemia associated with glimepiride therapy and titration. This review gives an overview on the efficacy and safety of linagliptin in comparison with other antidiabetic drugs in type 2 diabetes patients with renal and cardiovascular risk factors as well as an outlook on the perspective for linagliptin in this patient population in the future.