title: The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.
abstract: With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy.
authors.affiliation: Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138 Naples, Italy.
authors.forename: Liberata
authors.initials: L
authors.lastname: Sportiello
authors.affiliation: Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138 Naples, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Rafaniello
authors.affiliation: Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138 Naples, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Scavone
authors.affiliation: St Georges Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, UK.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Vitale
authors.affiliation: Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138 Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.affiliation: Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Second University of Naples, via de Crecchio 7, 80138 Naples, Italy. Electronic address: annalisa.capuano@unina2.it.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Capuano
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D060735:Pharmacovigilance; D012307:Risk Factors
chemical_list: D054795:Incretins; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: Cardiovascular profile; DPP-4 inhibitors; Diabetes; Incretin-based therapy; New Pharmacovigilance legislation; Safety