Canagliflozin-Mealtime Insulin Rescue

The Canagliflozin Mealtime Insulin Rescue study will enroll up to 40 subjects at the Atlanta
VA Medical Center. Subjects will be screened and enter a 2-week run-in period during which
they will switch to or continue on a diabetes treatment regimen of basal insulin before
supper and aspart insulin before meals. Run-in will be useful in evaluating compliance to
treatment and self-monitoring. After run-in, subjects will collect one week of baseline
glycemic data with regular pre-meal and fasting glycemic levels using both finger stick
testing and continuous glucose monitoring.

Subjects will be randomized at Visit 3 to 100 mg of canagliflozin or placebo. If well
tolerated, this dose will be increased to 300 mg of canagliflozin or placebo at Visit 4.

Diabetes management will be assured through regular contact with the study team (weekly calls
and clinic visits at Weeks 4, 8, 16 and 24). Management will be facilitated by diabetes
management software. Self-monitoring and continuous glucose monitoring will be repeated at
the end of study participation.

Inclusion Criteria:

- use of basal-bolus insulin

- onset of diabetes after age 30

- BMI less than 35

- eGFR at least 60 ml/mn

- Hb A1c 7.0-10.0%

- willingness to perform home glucose monitoring

- willingness to transmit glucose and medication information weekly

Exclusion Criteria:

- Type 1 diabetes

- Known peripheral artery disease

- Liver enzymes equal or more than 1.5 times the upper limit of normal

- Chronic heart failure NYHA class III or IV

- Current haemodialysis or peritoneal dialysis

- End stage liver disease, defined as acute or chronic liver disease and recent history
of one of the following: ascites, encephalopathy, variceal bleeding, bilirubin equal
or greater than 2.0 mg/dL, albumin equal or less than 3.5 g/ dL, prothrombin time
greater or equal to 4 seconds, INR greater than or equal to 1.7 or prior liver
transplant

- Known or suspected hypersensitivity to trial products or related products

- Female of child-bearing potential who is pregnant, breast-feeding or intends to become
pregnant or is not using adequate contraceptive methods as required by law or local
practice.

- Expected simultaneous participation in any other clinical trial of an investigational
medicinal product.

- Receipt of any investigational medicinal product within 30 days before randomization

- Current or past (within the last 5 years) malignant neoplasms (except basal cell and
squamous cell skin carcinoma)

- Any condition that in the investigator's opinion would make the subject unable to
adhere to the trial visit schedule and procedures

- Known history of non-compliance to treatment.