The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study
Condition: Diabetes Mellitus, Type 2; Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Metformin; Detemir; Liraglutide; Insulin Aspart
Intervention description: Metformin will be started at 500 mg daily (or continued at current dose)and weekly titrated to 2000 mg or maximum tolerated dose (at least 1000 mg/day); Insulin detemir will be started in both groups at 0.3 units/kg or conversion 1:1 from dose of basal insulin prior to randomization. The titration will be primarily patient-driven, based on our study protocol table. Additional physician driven titration will be allowed in both groups if patient fails to intensify basal insulin dose as directed.; Initial dose of 0.6 mg/day with weekly increments of 0.6 mg until dose of 1.8 mg/day or maximal tolerated dose (at least 1.2 mg/day)is reached; Insulin aspart will be initiated at a dose of 0.3 units/kg/day divided among the number of meals taken daily and titrated based on physician clinical judgment with the goal of pre-prandial BG 70-130 mg/dL and post-prandial BG <180
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Metformin; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Liraglutide; Insulin Detemir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 157.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus, Type 2; Insulin; Insulin, Long-Acting; Insulin, Short Acting; Detemir; Liraglutide; GLP-1; Glucagon Like Peptide; Metformin; Uncontrolled Diabetes; Elevated A1c; Incretins

Summary:

      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%).
    

Eligibility criteria:

        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.