title: The Place of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Therapeutics: A "Me Too" or "the Special One" Antidiabetic Class?
abstract: Incretin-based therapies, the most recent therapeutic options for type 2 diabetes mellitus (T2DM) management, can modify various elements of the disease, including hypersecretion of glucagon, abnormal gastric emptying, postprandial hyperglycaemia, and, possibly, pancreatic β cell dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) increase glucagon-like peptide-1 (GLP-1) availability and correct the "incretin defect" seen in T2DM patients. Clinical studies have shown good glycaemic control with minimal risk of hypoglycaemia or any other adverse effects, despite the reports of pancreatitis, whose association remains to be proved. Recent studies have been focusing on the putative ability of DPP-4 inhibitors to preserve pancreas function, in particular due to the inhibition of apoptotic pathways and stimulation of β cell proliferation. In addition, other cytoprotective effects on other organs/tissues that are involved in serious T2DM complications, including the heart, kidney, and retina, have been increasingly reported. This review outlines the therapeutic potential of DPP-4 inhibitors for the treatment of T2DM, focusing on their main features, clinical applications, and risks, and discusses the major challenges for the future, in particular the possibility of becoming the preferred therapy for T2DM due to their ability to modify the natural history of the disease and ameliorate nephropathy, retinopathy, and cardiovascular complications.
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, Coimbra University, 3000-548 Coimbra, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Godinho
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, Coimbra University, 3000-548 Coimbra, Portugal ; ESAV, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal.
authors.forename: Cristina
authors.identifier: 0000-0002-9913-875X
authors.initials: C
authors.lastname: Mega
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, Coimbra University, 3000-548 Coimbra, Portugal ; ESAV, Polytechnic Institute of Viseu, 3504-510 Viseu, Portugal.
authors.forename: Edite
authors.identifier: 0000-0002-6346-8319
authors.initials: E
authors.lastname: Teixeira-de-Lemos
authors.affiliation: Center for Neuroscience and Cell Biology-Institute for Biomedical Imaging and Life Sciences (CNC.IBILI) Research Unit, University of Coimbra, 3000-548 Coimbra, Portugal ; The Portuguese Diabetes Association (APDP), 1250-189 Lisbon, Portugal.
authors.forename: Eugénia
authors.initials: E
authors.lastname: Carvalho
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, Coimbra University, 3000-548 Coimbra, Portugal.
authors.forename: Frederico
authors.initials: F
authors.lastname: Teixeira
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, Coimbra University, 3000-548 Coimbra, Portugal ; Center for Neuroscience and Cell Biology-Institute for Biomedical Imaging and Life Sciences (CNC.IBILI) Research Unit, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Rosa
authors.identifier: 0000-0001-7828-2296
authors.initials: R
authors.lastname: Fernandes
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, Coimbra University, 3000-548 Coimbra, Portugal ; Center for Neuroscience and Cell Biology-Institute for Biomedical Imaging and Life Sciences (CNC.IBILI) Research Unit, University of Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Flávio
authors.identifier: 0000-0003-3401-9554
authors.initials: F
authors.lastname: Reis
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors