Effects of Metformin in Heart Failure Patients

Because of the state of insulin resistance in heart failure (HF), metformin, with its ability
to sensitize tissues to insulin, seems to be an ideal agent for managing type 2 diabetes
mellitus (DM) in HF. It reduces the concentration of glucose in blood by enhancing insulin
sensitivity, inducing greater peripheral uptake of glucose, and decreasing hepatic glucose
output. However, according to the package insert, it is contraindicated in all patients with
HF requiring pharmacologic treatment because of increased risk of lactic acidosis. The FDA
has now de-escalated this contraindication to a warning as the evidence is lacking regarding
an increased risk of lactic acidosis in patients with type 2 DM and HF who take metformin.

Hypothesis: In patients, who have diabetes type 2, are treated with metformin, and are
admitted for HF, metformin leads to reduced insulin requirements, as measured in units of
insulin, with no negative impact on patient safety.

Primary Objective: To test the hypothesis that continuing a patient's home metformin for
diabetes management while admitted to UK hospital will result in decreased utilization of
insulin as denoted by total units given.

Secondary Objectives: To test the hypothesis that administering metformin in HF patients
admitted to UK Hospital:

1. Results in similar glycemic control (targeting a blood glucose < 200mg/dL) when compared
with placebo along on the basis of basic metabolic panel glucose values. Both groups may
receive conventional inpatient hyperglycemia management with insulin products

2. Reduces drug and laboratory costs

3. Reduces hospital length of stay

4. Does not result in hypoglycemia (blood glucose < 60 mg/dL)

5. Reduced discharge medication errors related to diabetic medications

6. No observed increase in metabolic acidosis due to elevated lactate levels

7. Does not impact heart failure status (as indicated by trending NT-pro BNP levels)

Both the diagnosis and clinical management of patients with heart failure and type 2 diabetes
mellitus will be guaranteed by the application of standard guidelines internationally
recognized. All patients admitted to the Medicine / Cardiology Advanced Heart Failure at UK
Hospital will be evaluated for inclusion and exclusion criteria. Based on our power analysis
we plan to enroll 100 subjects total. Subjects will be enrolled from January 1, 2016 -
December 31, 2018 until 120 patients are enrolled, estimated study time frame is two years.

Inclusion Criteria:

1. Patients > / = 18 years of age

2. Admitted to the Medicine / Cardiology Advanced Heart Failure at UK Hospital

3. Carry a diagnosis of heart failure with or without preserved ejection fraction

4. Carry a diagnosis of type 2 diabetes mellitus

Exclusion Criteria:

1. Patients <18 years of age

2. Prisoners

3. Terminal state

4. Known adverse reaction or hypersensitivity to metformin administration

5. Pregnancy

6. Pathological conditions in which metformin administration is clinically
contraindicated (Patients with acute or chronic metabolic acidosis, serum creatinine >
1.4 mg/dL in females, serum creatinine > 1.5 mg/dL in males)

7. Patients with acute cardiovascular collapse, acute myocardial infarction, septicemia

8. Patients carrying a diagnosis of type 1 diabetes mellitus

9. Patients admitted with diabetic ketoacidosis or hyperosmotic hyperosmolar state.

10. Patients who experience diabetic ketoacidosis or hyperosmotic hyperosmolar state at
any point during their hospital admission.

11. Patients admitted with a subcutaneous insulin pump

12. Patients who, at the discretion of the Medicine / Cardiology Advanced Heart Failure
service, required an endocrinology consult during their hospitalization where the
endocrine consult service is opposed to utilizing metformin in a particular patient