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

The University of Texas System (UT)

Status and phase: Completed; Phase 4

Conditions: Diabetes; Diabetes Mellitus, Type 2

Treatments: Drug: Liraglutide; Drug: Metformin; Drug: Insulin Aspart; Drug: Detemir

Study type: Interventional

Funder types: Other

Identifiers

NCT01966978

STU 072013-030

Details and patient eligibility

About

The aim of this clinical trial is to assess and compare the effect of insulin detemir in combination with liraglutide and metformin versus insulin detemir in combination with insulin aspart and metformin in subjects with very uncontrolled Type 2 Diabetes (A1c > 10%).

Full description

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.

Enrollment: 157 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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157 participants in 2 patient groups

Control: Metformin, Insulin Detemir, Insulin Aspart

Active Comparator group

Description:

Metformin titrated to max tolerated dose (at least 1000 mg/day); Insulin detemir titrated based on the study protocol; Insulin Aspart titrated by the physician

Treatment:

Drug: Detemir

Drug: Insulin Aspart

Drug: Metformin

Metformin, insulin determir, Liraglutide

Active Comparator group

Description:

Metformin titrated to max tolerated dose (at least 1000mg/day); Insulin detemir titrated based on the study protocol"; Liraglutide titrated to max tolerated dose (at least 1.2 mg/day)

Treatment:

Drug: Detemir

Drug: Liraglutide

Drug: Metformin