title: Novel antidiabetic drugs and cardiovascular risk: Primum non nocere.
abstract: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes.
  
  
  
  The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs. Endpoints of CV mortality, myocardial infarction (MI), stroke and hospitalization for heart failure (HF) were included in the most recent clinical studies on novel antihyperglycemics. These are: the incretin mimetics glucagon-like peptide 1 (GLP-1) receptor agonists (GLP1-RA), the incretin enhancers dipeptidylpeptidase-4 (DPP-4) inhibitors (DPP4-I or gliptins), and the sodium-glucose cotransporter (SGLT2) inhibitors (SGLT2-I or gliflozins). The studies ELIXA and EXAMINE, testing lixisenatide and alogliptin, respectively, revealed non-inferiority versus placebo in terms of CV safety. The SAVOR-TIMI 53 results confirmed overall CV safety of saxagliptin, but raised a warning related to the increase in the risk of hospitalization for HF in the saxagliptin group. Recently, TECOS revealed a particularly favorable CV profile for sitagliptin while EMPA-REG showed a significant CV risk reduction in empagliflozin treated subjects. Ongoing studies will provide additional data on CV safety for other GLP1-RAs, DPP4-I and SGLT2-I.
  
  
  
  Results of safety outcome studies focused on CV events, including HF and mortality for CV causes, are not homogeneous. A critical analysis of these studies may help cardiologists and diabetes specialists to adapt their therapeutic choices to individual patients.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma and Division of Endocrinology, Azienda Ospedaliera Universitaria of Parma, Parma, Italy.
authors.forename: R C
authors.initials: RC
authors.lastname: Bonadonna
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Borghi
authors.affiliation: Department of Medicine and Ageing Sciences and Inter-Departmental Center CeSI-MeT, University d'Annunzio, Chieti, Italy. Electronic address: consoli@unich.it.
authors.forename: A
authors.initials: A
authors.lastname: Consoli
authors.affiliation: Cardiology, Dept. of Clinical and Molecular Medicine, University of Rome Sapienza, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Volpe
mesh_terms: D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005960:Glucosides / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D061214:Patient Safety; D018579:Patient Selection; D018570:Risk Assessment; D012307:Risk Factors; D000068900:Sitagliptin Phosphate / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D007004:Hypoglycemic Agents; D054795:Incretins; C570240:empagliflozin; D000068900:Sitagliptin Phosphate
keywords: Antihyperglycemic drugs; Cardiovascular risk; Diabetes