The overall impact of glucose lowering on vascular complications and major clinical outcomes, including mortality, in type 2 diabetes is still an open issue. While intensive glucose control has undoubted benefit for microvascular end points, the relationship between glucose-lowering approaches and reduced incidence and/or progression of macrovascular complications is less clear. This review article will discuss the effect of glucose lowering per se as well as the effects of specific glucose-lowering therapies on vascular outcomes in type 2 diabetes. The role of lifestyle changes on cardiovascular outcomes will be also addressed. Recent analyses from large cardiovascular outcome studies (ACCORD, ADVANCE, and VADT) provide new information on factors that modulate the impact of intensive glucose lowering on outcomes, helping to identify the specific clinical characteristics of the patients receiving the intervention that would show a better response. While several studies on cardiovascular outcomes with diabetes drugs are available, they do not clearly highlight a benefit from using a specific medication or will require additional evidence, as for the sodium-glucose cotransporter 2 blockers.
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