Is There Evidence That Oral Hypoglycemic Agents Reduce Cardiovascular Morbidity/Mortality? Yes

Athough type 2 diabetes is a heterogeneous condition encompassing multiple metabolic and vascular alterations, it can be easily described as a disease characterized by chronic hyperglycemia and increased cardiovascular (CV) risk. Hyperglycemia is the diagnostic criterion for diabetes, the target for antidiabetic therapy, and, together with A1C, the marker of glycemic control. Progressive worsening of glycemic control has been described in type 2 diabetic patients irrespective of initial form of treatment, leading the U.K. Prospective Diabetes Study (UKPDS) investigators to describe such changes as the “natural history” of the disease (1). Still, maintaining good glycemic control is crucial, since it is associated with marked reduction in the risk of developing retinopathy, nephropathy, and neuropathy in both type 1 (2) and type 2 diabetic patients (1). But it is CV disease that worsens long-term prognosis in type 2 diabetes (3), to the point that diabetes has been proposed as a CV risk equivalent owed to the observation that 10-year risk for major coronary events approximates the risk in CHD in patients without diabetes with previous CV events (4), increased case fatality rate after myocardial infarction, and worse overall prognosis after CHD (5). In diabetic patients, even after correction for known CV risk factors, the incidence of myocardial infarction or stroke is two- to threefold higher than in the nondiabetic population, with a twofold increase in risk of death (6), suggesting that some feature of diabetes must confer excessive propensity toward CV disease. Can this feature be hyperglycemia? No better issue can be chosen for debate. From an epidemiological point of view, there is evidence that the risk of CV mortality increases with the increase of plasma glucose concentrations (7) and A1C values (8). Moreover, multiple atherogenic mechanisms have been identified that can be activated by hyperglycemia (9). In spite of evident …