Over the past decades, the incidence of type 2 diabetes mellitus (T2DM) has been rapidly rising worldwide, driven primarily by an increasing incidence of obesity and sedentary lifestyles. Patients with T2DM can develop severe microvascular complications, related to persistently elevated glucose concentrations, including blindness, renal failure, or nerve damage, and have a higher incidence of atherosclerotic vascular disease with complications such as myocardial infarction (MI), stroke, and amputations due to vascular insufficiency. Improved glucose control reduces the incidence of microvascular complications in patients with both type 1 diabetes mellitus (T1DM) and T2DM. The impact of improved glycemic control on macrovascular events is less well established.
The primary objectives of the study are to assess the effect of canagliflozin plus standard of care relative to placebo plus standard of care on CV risk and assess the safety and tolerability of canagliflozin plus standard of care relative to placebo plus standard of care in subjects with T2DM, with inadequate glycemic control, who have a history or high risk of CV disease.