OBJECTIVES: Type-2 diabetes is the most common metabolic disease in Italy and in developed countries. It is the sixth leading chronic disease by diffusion with a crude prevalence of 4.9%. It is estimated that about 3,000,000 Italians suffer from this pathology. In the last decade, the new class of incretin-based therapies entered the arena, but their place in therapy remains difficult to determine because of limited long-term clinical data on both effectiveness and safety, and the high cost of therapy. Both injectable glucagon-like peptide1(GLP-1) receptor agonists (incretin-mimetics) and orally-administered inhibitors of dypeptidylpeptidase-4(DPP-4) produce a significant improvement in glycemic control especially when combined with metformin, similar to other second-line therapies, but additional advantages with respect to weight gain and overall hypoglycemia. In 2008 AIFA established a Monitoring Registry through which collecting and monitoring the safety and the efficacy profiles of new antidiabetic drugs. METHODS: Data collected from the Monitoring Registry from 2008 to 2011 were analyzed. An estimation of population enrolled, NHS-expenditures and median cost for patients were calculated for the antidiabetic drugs which entered in the Registry. RESULTS: AIFA Antidiabetic Monitoring Registry enrolled 135,954 patients for the period of observation. 79,211 patients (58%) were treated with DPP-4 (saxagliptin, vildagliptin and sitagliptin associated or not with metformin) and 56,743 patients (42%) with GLP-1 analogous (liraglutide and exenatide) with an economic NHS burden on Registry respectively equal to €34,675,414 (55%) and €28,649,091 (45%). The daily mean cost per patient related to the drugs included in the Registry was around €3. CONCLUSIONS: The safety and efficacy profiles of drugs monitored in the Italian real-world clinical practice are similar to those recorded during phase 2-3 registration clinical trials. Data collected through Registry allows performing a cost-effectiveness analysis and a cost-impact for NHS comparing both the monitored drugs among them and the other therapeutic treatments