Male sex is a major cardiovascular risk factor in the general population, with men showing higher age-adjusted prevalence of cardiovascular disease than women. Diabetes, another major cardiovascular risk factor, affects cardiovascular risk differentially between men and women. Data from prospective observational studies showed that women with diabetes had greater relative risk of cardiovascular events than men with diabetes, leading to a smaller difference between diabetic men and women than between non-diabetic men and women in terms of cardiovascular disease. This excess relative risk concerns cardiovascular death, coronary heart disease, stroke and heart failure. It is greatest in the youngest age group and decreases gradually with age. Although many mechanisms have been proposed to explain the greater cardiovascular burden in women with diabetes, little is known about the impact of diverse anti-hyperglycemic drugs on cardiovascular events according to sex. Hence, cardiovascular outcomes trials provide a unique opportunity to study the impact of novel anti-hyperglycemic drugs on cardiovascular outcomes in men and women with type-2 diabetes. Here, we present an overview of the epidemiological data concerning sex-related differences in cardiovascular disease in people with diabetes, with a focus on the effects of novel anti-hyperglycemic drugs on cardiovascular outcomes in men and women. In addition, we summarize proposed mechanisms to explain these differences, with relevant references for the interested reader.