title: Novel therapeutic targets of metformin: metabolic syndrome and cardiovascular disease.
abstract: BACKGROUND
  Metformin is a widely used drug in the treatment of type 2 diabetes mellitus (T2DM). However, it is becoming an attractive drug to manage patients with pre-diabetes and to possibly prevent cardiac remodeling and fibrosis and heart failure.
  
  
  METHODS
  In this review, we highlight the novel therapeutic targets of metformin with a special emphasis on cardiovascular disease. We discuss its key mechanisms of action and new signaling pathways that could partially account for its effect. Furthermore, metformin's role in the management of patients with metabolic syndrome is debated, emphasizing its potential to prevent diabetic heart disease. On the other hand, intense research is ongoing to clarify if metformin will be a future drug to target ischemia-reperfusion injury in the setting of myocardial ischemia.
  
  
  CONCLUSIONS
  In the following years, one should look carefully at basic science results to successfully design and conduct clinical trials, emphasizing patients without full-blown T2DM, but who otherwise might have increased insulin resistance. Topics such as the prevention of cardiac fibrosis and heart failure with preserved ejection fraction, the attenuation of ischemia-reperfusion injury on an acute coronary syndrome and the post-myocardial infarction left ventricle remodeling surely deserve a special interest and should be faced as potential therapeutic targets for metformin.
authors.affiliation: Gaia Hospital Centre, Department of Cardiology , Vila Nova de Gaia 4400-129 , Portugal +00351227865100 ; ricardoladeiraslopes@gmail.com.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ladeiras-Lopes
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fontes-Carvalho
authors.forename: Nuno
authors.initials: N
authors.lastname: Bettencourt
authors.forename: Francisco
authors.initials: F
authors.lastname: Sampaio
authors.forename: Vasco
authors.initials: V
authors.lastname: Gama
authors.forename: Adelino
authors.initials: A
authors.lastname: Leite-Moreira
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy*; D008687:Metformin / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D011236:Prediabetic State / Q000150:complications / Q000188:drug therapy
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: cardiovascular disease; heart failure; ischemic heart disease; metabolic syndrome; metformin