Efficacy and Safety of a Glargine-based Hospital Discharge Algorithm in Coronary Artery Bypass Graft (CABG) Patients

Hospital discharge represents a critical time for ensuring a safe transition to the
outpatient setting and reducing the need for emergency department visits and
re-hospitalization. Poor coordination of patient care and education on insulin administration
at the time of patient discharge to home may be associated with medical errors that may
increase risk of hypoglycemia, hyperglycemia and hospital readmission. No prospective studies
have examined the impact of a discharge treatment regimen after cardiac surgery. Therefore,
this study aims to determine the efficacy and safety of an HbA1c based treatment algorithm in
controlling blood glucose (BG) after discharge. The total duration of the study is 3 months.

This study will include diabetic and non-diabetic subjects who participated in the American
Diabetes Association (ADA) trial entitled "Intensive Insulin Therapy in Patients Undergoing
Coronary Artery Bypass Surgery." The ADA study is a two-arm randomized multicenter,
open-label controlled trial aimed to determine if intensive insulin control with a BG target
of 100-140mg/dl will reduce perioperative complications compared to a conventional BG control
with a target of 141-180 mg/dl in hyperglycemic subjects who undergo coronary artery bypass
graft surgery (CABG).

Treatment recommendations at discharge:

- Patients with admission HbA1c < 7%:

- Patients without a history of diabetes not requiring subcutaneous (SC) insulin in
the hospital will be discharged on no antidiabetic therapy.

- Patients without a history of diabetes requiring SC insulin therapy in the hospital
will be discharged on metformin monotherapy. A patient without a history of
diabetes who requires SC insulin is likely a newly diagnosed diabetic. The HbA1c
value will be important to confirm the diagnosis. If the HbA1c is >6.5%, he/she
will be diagnosed with diabetes. We do not anticipate that a patient without a
history of diabetes and with an HbA1c <6.5% will require insulin treatment or oral
agents long-term. Those patients will be discharged on no anti diabetic therapy
with repeated testing after discharge to rule out diabetes.

- Patients with a history of diabetes will be discharged on their same outpatient
antidiabetic regimen (diet, oral antidiabetic agents and/or insulin).

- Assure there are no contraindications to oral agents (i.e.Thiazolidinediones (TZDs)
and heart failure; metformin and renal failure or heart failure).

- Patients with Admission HbA1c between 7% and 9%:

- Treatment naïve patients not on any pharmacologic treatment prior to admission will
be discharged on metformin monotherapy or a combination of metformin and a single
dose of basal (glargine) insulin at 50% of total daily hospital dose.

- Patients treated with oral antidiabetic agents or glucagon-like peptide-1 (GLP1)
analogs prior to admission will be discharged on pre-admission oral antidiabetic
therapy plus a single dose of glargine insulin at 50% of the total daily hospital
dose.

- Patients treated with combination of oral antidiabetic agents and basal insulin
(NPH insulin also known as Neutral Protamine Hagedorn insulin, glargine, detemir)
prior to admission will be discharged on pre-admission oral antidiabetic therapy
plus a single dose of glargine insulin or with basal bolus insulin regimen at 50%
of total daily hospital dose.

- Patients not to be treated with oral agents will be discharged on glargine
monotherapy or basal bolus at 100% of inpatient total daily dose.

- Admission HbA1c ≥ 9% prior to admission:

- Discharge on basal bolus regimen at same inpatient total daily insulin dose.

- Basal insulin (glargine) once daily, at the same time of the day.

- Rapid-acting insulin (glulisine) before meals.

- Alternative treatment: If no contraindications to oral agents (i.e.,
Thiazolidinediones (TZDs) and heart failure; metformin and renal failure) restart
oral agents in combination to glargine once daily at 80% of total daily hospital
dose.

Inclusion Criteria:

1. Males or females between the ages of 18 and 80 years undergoing primary coronary
artery bypass graft surgery (CABG).

2. Post surgical hyperglycemia (Blood glucose >140 mg/dl)

3. Patients with and without a history of type 2 diabetes

Exclusion Criteria:

1. Patients with severely impaired renal function (serum creatinine ≥3.0 mg/dl or a
glomerular filtration rate < 30 ml/min) or clinically significant hepatic failure.

2. Subjects with acute hyperglycemic crises such as diabetic ketoacidosis (DKA) and
hyperosmolar hyperglycemic states.

3. Moribund patients and those at imminent risk of death (brain death or cardiac
standstill).

4. Patients or next-to-kin with mental conditions rendering the subject or family member
unable to understand the nature, scope, and possible consequences of the study.

5. Female subjects who are pregnant or breast-feeding at time of enrollment into the
study.