BACKGROUND AND OBJECTIVES:Diabetes mellitus is a complex, progressive disease that can lead to complications if it is not strictly controlled. The literature suggests that only 50 % of Italian patients with type 2 diabetes mellitus (T2DM) achieve guideline-recommended levels of glycaemic control, suggesting that treatment regimens need to be improved. The present study aimed to evaluate the effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors in terms of glycaemic control, body weight and lipid profile in a series of patients with T2DM attending a diabetes outpatient facility. METHODS:This was an observational retrospective study performed on a series of patients with T2DM attending our three outpatient clinics. The study included 360 patients with T2DM of both sexes, aged between 30 and 85 years, with a body mass index (BMI) of 22-45 kg/m(2) who were uncontrolled [glycated haemoglobin (HbA(1c)) 7.1-10 %] despite dietary restrictions or treatment with pharmacological therapy. Patients included in the analysis received therapy with a DPP-4 inhibitor (sitagliptin, n = 244; vildagliptin, n = 97; saxagliptin, n = 19). RESULTS:Vildagliptin reduced HbA(1c) by 1.2 % compared with sitagliptin and saxagliptin (-0.9 %) from a baseline of 8 % (similar in all groups). The greatest decrease in fasting plasma glucose was seen with vildagliptin (-37 mg/dL) compared with sitagliptin and saxagliptin (-20 and -29 mg/dL, respectively). A greater reduction in total cholesterol was achieved with vildagliptin (-24 mg/dL) than with sitagliptin (-11 mg/dL) and saxagliptin (-3.6 mg/dL). Effectiveness was maintained in all age groups, provided disease duration was short (~5 to 6 years). Adverse effects were mild and transient and did not require treatment discontinuation. CONCLUSIONS:DPP-4 inhibitors are a viable option in patients with T2DM not adequately controlled by existing therapy. They demonstrate comparable efficacy to other antidiabetic medicines with regard to HbA(1c) reduction. The positive changes in the lipid profile make DPP-4 inhibitors a particularly interesting class of drugs; however, further studies are needed to confirm their true impact on cardiovascular risk in a real-world setting.