title: DPP-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials.
abstract: Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA(1c) reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin-SU or pioglitazone-SU combination. Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA(1c) and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-to-head trial demonstrated the non-inferiority of saxagliptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials.
authors.affiliation: Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Sart Tilman (B35), University of Liège, Liège, Belgium. andre.scheen@chu.ulg.ac.be
authors.forename: A J
authors.initials: AJ
authors.lastname: Scheen
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069476:Linagliptin; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D009570:Nitriles / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011687:Purines / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use; D014498:Uracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077597:Vildagliptin; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D000218:Adamantane; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D008687:Metformin; D009570:Nitriles; D010880:Piperidines; D011687:Purines; D011719:Pyrazines; D011759:Pyrrolidines; D011799:Quinazolines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; D014498:Uracil; D000077597:Vildagliptin; C517652:hemoglobin A1c protein, human; C502994:saxagliptin; C520853:alogliptin