title: Effects of Dipeptidyl Peptidase 4 Inhibitors and Sodium-Glucose Linked coTransporter-2 Inhibitors on cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis.
abstract: BACKGROUND
  Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4-Is and SGLT2-Is on CV events and mortality by meta-analysis.
  
  
  METHODS
  Randomized trials enrolling more than 200 patients, comparing DPP-4-Is or SGLT2-Is versus placebo or active treatments in patients with DM, and reporting at least one event among all-cause and CV mortality, stroke, myocardial infarction (MI) and new onset of heart failure (HF), were included.
  
  
  RESULTS
  157 randomized trials (114 on DPP4-Is and 43 on SGLT2-Is) enrolling 140,470 patients (107,100 in DPP4-I and 33,370 in SGLT2-I studies) were included in the analysis. Compared to control, treatment with DPP4-Is did not affect all-cause (RR: 1.010; 95% CI: 0.935-1.091) and CV (RR: 0.975; CI: 0.887-1.073) mortality as well as risk of MI (RR: 0.915; CI: 0.835-1.002), stroke (RR: 0.933; CI: 0.820-1.062) and HF (RR: 1.083; CI: 0.973-1.205). Treatment with SGLT2-Is significantly reduced the risk of all-cause death by 28% (RR: 0.718; CI: 0.613-0.840), CV death by 33% (RR: 0.668; CI: 0.544-0.821), MI by 20% (RR: 0.803; CI: 0.668-0.965) and HF by 35% (RR: 0.652; CI: 0.517-0.823) without effect on stroke (RR: 1.158; CI: 0.912-1.469).
  
  
  CONCLUSIONS
  DPP4-Is show a safe CV profile as they do not affect mortality and CV events, including HF, in patients with type 2 DM. SGLT2-Is are associated with improved CV outcome and survival in DM patients.
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Savarese
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: D'Amore
authors.affiliation: Department of Systems Medicine, University Tor Vergata, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Federici
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: De Martino
authors.affiliation: Villa dei Fiori, Acerra, Napoli, Italy; Mount Sinai Medical School, New York, United States.
authors.forename: Santo
authors.initials: S
authors.lastname: Dellegrottaglie
authors.affiliation: Istituto Diagnostico Varelli, Naples, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Marciano
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrazzano
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Losco
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lund
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.affiliation: Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy; Cardiovascular and Cell Sciences Research Institute, St George's University of London, London, United Kingdom.
authors.forename: Giuseppe M C
authors.initials: GM
authors.lastname: Rosano
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. Electronic address: fpperron@unina.it.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone-Filardi
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
keywords: Cardiovascular; Dipeptidyl Peptidase 4 Inhibitors; Outcomes; Sodium-Glucose Linked coTransporter-2 Inhibitors; Type 2 diabetes mellitus