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 glucosedependent 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 m 2 ) 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.

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

“…The efficacy and safety of linagliptin in comparison with other antidiabetic drugs in T2DM patients with renal and cardiovascular risk factors have been recently reviewed as well as an outlook on the perspective for linagliptin in this patient population in the future [76].…”

“…Therefore, it can be used in all stages of CKD without dose adjustments [76]. The influence of various degrees of CKD on the exposure of linagliptin was assessed in subjects with and without T2DM [41].…”

Managing diabetes in hospitalized patients with chronic kidney disease

“…48 However, except for linagliptin, dose reduction is recommended in patients with CKD stage 3 and higher. [49][50][51][52] GLP-1 receptor agonists. Drugs of this class are potent agents for the reduction of glucose in the outpatient setting but are relatively contraindicated if the GFR is less than 30 mL/min, and they are currently not used in the hospital.…”

Management of patients with type 2 diabetes and mild/moderate renal impairment: profile of linagliptin

“…Dose adjustments of linagliptin or the determination of the eGFR for calculating drug accumulation are therefore not necessary in patients with CKD. 24 , 25 …”

“…The renal function therefore does not have to be monitored solely for the sake of putative dose calculations for the antidiabetic therapy. 25 , 43 , 49 Table 1 illustrates the indications and contraindications for antidiabetic medications in relation to the kidney function. Furthermore, the renal function remained stable with the linagliptin therapy.…”