Introduzione Circa 350 milioni di persone nel mondo sono affette da diabete mellito di tipo 2 (DM2), patologia correlata ad un elevato rischio di mortalità, principalmente per cause cardiovascolari [1]. Un nuovo target terapeutico per il trattamento di tale patologia è rappresentato dalle incretine, ormoni prodotti a livello intestinale in seguito all'assun-zione di cibo e responsabili di circa il 60% della secrezione di insulina. L'effetto in-cretinico è dovuto principalmente a due ormoni: il

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... LP-1 (glucagon-like peptide 1) e il GIP (glucose insulinotropic polipeptide, chiamato inizialmente anche gastric inhibitory polipeptide) [2]. Il GLP-1 è un peptide di 30/31 aminoacidi prodotto dalle cellule L dell'ileo e colon, mentre il GIP è un peptide di 42 aminoacidi prodotto dalle cellule K del duodeno e digiuno prossimale. Una volta rilasciati, tali ormoni stimolano il pancre-as a produrre più insulina, per poi essere rapidamente (1-2 minuti) inattivati dall'en-zima dipeptidil peptidasi 4 (DPP-4) [3]. La DPP-4 è un aminopeptidasi di membrana ampiamente espressa in molti tessuti, come fegato, polmone, rene, intestino, linfociti Key words Incretin mimetics Incretin enhancers Type 2 diabetes Place in therapy Adverse drug reactions Abstract Incretin mimetics (GLP-1 analogues) and enhancers [dipeptidyl peptidase-4 (DPP-4) inhibitors] are two new classes of therapeutic agents for the treatment of type 2 diabetes. They are innovative drugs because of their new mechanism of action: the potentiation of incretin hormones signalling (e.g. GLP-1). Although this is the first time that drugs influence the effects of incretin hormones, they represent only a potential therapeutic innovation because pre-marketing studies did not show evidences of their major benefits over other antidiabetic drugs. In clinical studies these drugs were well-tolerated. However, due to their recent marketing approval there is not a complete knowledge on their tolerability, in particular about rare events. The most common adverse reactions (ADRs) with incretin mimetics were nausea, vomiting and diarrhoea, which generally diminish over time. Moreover, these two new categories are less associated to several specific ADRs of known treatments of type 2 diabetes (e.g. metformin and sulphonylurea derivatives), such as weight gain and hypoglycaemias. Although ADRs of incretin-based therapy are generally of mild to moderate severity, recent studies have described more severe reactions, such as hypersensitivity reactions, acute pancreatitis, renal failure, infection, and pancreatic and medullar thyroid cancer. In February 2008, the Italian Regulatory Agency of Medicines (AIFA) started an Anti-diabetes Drugs Register, which concluded in August 2010. The aims of the Register were to define the place of these new drugs in therapy and to verify their prescribing appropriateness, effectiveness and safety. The results showed a different prescriptive approach by medical doctors, with a prevalent use in Southern Italy. Only 65% of 1116 ADRs in the Register were sent by reporters to the National Network of Pharmacovigilance. This fact represents a great limitation of the Register. Currently, new molecules are in development or in process of approval. However, further studies are required to establish the role of GLP-1 analogues and DPP-4 inhibitors in diabetes treatment, in particular as an alternative to insulin or in association with insulin therapy.