CANVAS - CANagliflozin cardioVascular Assessment Study

The study will evaluate canagliflozin compared to placebo on CV events including CV death,
heart attack, and stroke in patients with T2DM, whose diabetes is not well controlled at the
beginning of the study and who have a history of CV events or have a high risk for CV events.
The study includes 3 substudies which will compare the effectiveness of lowering blood
glucose and assess the safety of canagliflozin relative to placebo in patients receiving
specific commonly-used diabetes agents. 4,330 participants will be randomly assigned to
treatment with 1 of 2 doses of canagliflozin (100 or 300 mg) or placebo, in a 1:1:1 ratio.
This study was originally designed to last for up to 9 years. As per FDA post-marketing
requirements for canagliflozin, the study's last subject last visit will now occur when
enough MACE events (ie, CV death, nonfatal myocardial infarction, nonfatal stroke) are
accumulated between the CANVAS (this study) and CANVAS-R studies. The completion target was
reached in February 2017.

Inclusion Criteria:

- Patients must have a diagnosis of type 2 diabetes mellitus and greater than or equal
to (>=) 30 yrs old with history of cardiovascular (CV) event, or >= 50 yrs old with
high risk of CV events

- Patients must have inadequate diabetes control (as defined by glycosylated hemoglobin
greater than or equal to 7.0% to less than or equal to 10.5% at screening) and be
either (1) not currently on diabetes drug therapy or (2) on therapy with any approved
class of diabetes drugs

Exclusion Criteria:

- A history of diabetic ketoacidosis, type 1 diabetes mellitus, pancreas or beta-cell
transplantation, or diabetes secondary to pancreatitis or pancreatectomy

- History of one or more severe hypoglycemic (ie, very low blood sugar) episode within 6
months before screening