Combination therapy for the improvement of long-term macrovascular and microvascular outcomes in type 2 diabetes: Rationale and evidence for early initiation

Diabetes is a leading cause of macrovascular and microvascular complications that can increase the risk of mortality if not properly managed. Proper glucose control can reduce the incidence of these complications, in particular those of the microvasculature. Over the last ~ 10 years, the cardiovascular safety of glucose-lowering drugs has come to the forefront of diabetes management and clinical trial design. While early combination therapy improves glycemic control, its impact on long-term outcomes, is not as clearly understood. The objective of this review is to examine the evidence of early combination therapy for the treatment of type 2 diabetes mellitus as it relates to studies of long-term microvascular and macrovascular outcomes.