Aim: The aim of this study was to show ali the currently available information about the cardiovascular safety of antidiabetic agents that are administered orally and subcutaneously, with the exception of insulin preparations. Large clinical trials have been launched in the past few years due to new FDA guidelines on the necessity of checking the cardiovascular profile of newly approved drugs used in the treatment of type 2 diabetes. Cardiovascular risk in diabetic patients increased several times compared to the rest of the population and it is important to take such an outcome into account when choosing antidiabetic therapy. Chronic complications of diabetes type 2 are a major problem in treatment and a major cause of morbidity and mortality. They have an effect on the quality of life and the cost of the overall treatment. The most important macrovascular complications of type 2 diabetes are coronary heart disease, cerebrovascular disease and peripheral vascular disease. Myocardial infarction and stroke are the leading causes of death in diabetes type 1 and 2. Materials and methods: The work reviewed the available literature on the topic and lists current knowledge and assessment of the impact of antidiabetic drugs on the cardiovascular system, with particular emphasis on macrovascular complications of diabetes and long-term monitoring of the incidence of major cardiovascular events during the use of these medications. Articles in relevant scientific journals, various congress reports, chapters of textbooks on the subject of endocrine diseases and relevant guidelines of the Croatian, European and international associations for the treatment of diabetes type 2 diabetes will serve as material for the preparation of this work. Results: This paper presents the available data on the results of the completed large clinical cardiovascular outcomes study of antidiabetic agents that are administered orally and subcutaneously, and available data on clinical trials that are currently underway. Clinical implications of these results and the possible impact on the relevant guidelines for the choice of antidiabetic therapy in patients with type 2 diabetes with existing cardiovascular disease or at high cardiovascular risk are listed in the discussion after each study. Ali the important groups of antidiabetic agents and their effects on the cardiovascular system (metformin, sulfonylurea, glinides, thiazolidinediones, DPP-4 inhibitors, GLP-1 agonists, aglucosidase inhibitors, SGLT2 inhibitors, etc.) are described, while assessing cardiovascular safety during their long-term application. Conclusion: Based on studied clinical results of cardiovascular outcomes and cardiovascular risk assessment it was concluded that some groups of antidiabetic agents have a beneficial effect on the cardiovascular system, but also have some clear clinical limitations due to possible increased cardiovascular risk. Also, cases where the assessment of cardiovascular risk is still not fully understood are highlighted. Properly designed studies according to guidelines of regulatory agencies will lead to new knowledge and strong evidence for the cardiovascular safety of new and existing antidiabetics and further investigate their possible beneficial effects on the cardiovascular system in order to better treat type 2 diabetes.