title: Pharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes.
abstract: Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin). Drug-drug pharmacokinetic interaction studies do not show any significant changes in peak concentrations (Cmax) and total exposure (area under the curve of plasma concentrations [AUC]) of either drug when they were administered together orally compared with corresponding values when each of them was absorbed alone. Two fixed-dose combinations (FDCs) are already available (dapagliflozin-saxagliptin, empagliflozin-linagliptin) and others are in development (ertugliflozin-sitagliptin). Preliminary results show bioequivalence of the two medications administered as FDC tablets when compared with coadministration of the individual tablets. Dual therapy is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. SGLT2I and DPP-4I could be used as initial combination or in a stepwise approach. The additional glucose-lowering effect appears to be more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Combining the two pharmacological options is safe and does not induce hypoglycaemia.
authors.affiliation: Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, CHU Sart Tilman (B35), 4000, Liège 1, Belgium. andre.scheen@chu.ulg.ac.be.|Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium. andre.scheen@chu.ulg.ac.be.
authors.forename: André J
authors.initials: AJ
authors.lastname: Scheen
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068896:Canagliflozin / Q000493:pharmacokinetics / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D004151:Dipeptides / Q000493:pharmacokinetics / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005960:Glucosides / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D000069476:Linagliptin / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin; C529054:dapagliflozin; D000069476:Linagliptin; C502994:saxagliptin; C570240:empagliflozin; D000218:Adamantane; D000068900:Sitagliptin Phosphate