Introduction: Type 2 Diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constrain in the management of this disease. We evaluated the use, the adherence and the dsaftey of antidiabetic drugs in patients with T2DM. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug adherence was measured in agreement to the European Society for Patient Adherence, Compliance and Persistence Medication Adherence Reporting Guideline. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 12,170 medical records of 7 general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Enrolled patients were stratified as high (35%), medium (41%) and low (24%) adherence. Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (P = 0.023). During the study we recorded 26 ADRs that was correlated with sex (women) and insulin treatment. Conclusion: this real-life study shows that patients with T2DM have high adherence probably related dto a low number of ADRs