The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study

The aim of this study is to compare a GLP-1 plus basal insulin and metformin treatment
regimen to a basal-bolus plus metformin treatment regimen in patients with very uncontrolled
(HbA1c>10%) type 2 diabetes. The investigators will compare the two regimens with respect to
efficacy in improving glycemic control, rate of hypoglycemia, change in weight, effect on
patient quality of life, treatment burden, physician time, as well as healthcare related
cost. The investigators hypothesize that at 26 weeks from randomization the two treatment
regimens will have similar percentage of patients reaching A1c levels <7.0%, while more
patients on the GLP-1 plus basal insulin strategy will achieve the composite end point of A1c
levels <7.0% without severe hypoglycemia or significant weight gain.

Inclusion Criteria:

1. Clinical diagnosis of type 2 diabetes with confirmed HbA1c level >10% at time of
enrollment, regardless of prior or current treatment regimens, or time since diagnosis.

Exclusion Criteria:

1. Age <18 as the feasibility and safety of this treatment regimen should be first
established in the adult population; if successful, a subsequent pediatric study will
be proposed;

2. Type 1 diabetes as purposefully withholding meal-time insulin is contraindicated;

3. Clinical state requiring inpatient admission/treatment;

4. Contraindication or strong cautions to any of the study medications:

1. Creatinine above 1.4 mg/dl for women and 1.5 mg/dl for men (per metformin label)

2. History of lactic acidosis (per metformin label)

3. Advanced hepatic or cardiac disease (per metformin label)

4. Age >80 years (per metformin label)

5. Chronic alcohol use (>14 drinks/week)

6. History of pancreatitis (per liraglutide label)

7. Personal or family history of medullary thyroid cancer or MEN syndrome (per
liraglutide label)

8. Pregnancy and lactation (per liraglutide label)

5. Any serious or unstable medical condition as it would interfere with treatment
assignment as well as outcome measurement;

6. Any scheduled elective procedures/surgeries;

7. Active infections, including osteomyelitis;

8. Not willing to participate, unable to keep projected appointments, unwillingness to
receive injectable treatment; unwillingness to perform 7-point glucose profiles over 2
consecutive days the weeks prior to Randomization (visit 1)and the week prior to visit
6

9. Non English speaking.