Clinical trial NCT01966978: The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study
Official title: The Effect of Simple Insulin Detemir Titration, Metformin Plus Liraglutide Compared to Simple Insulin Detemir Titration Plus Insulin Aspart and Metformin for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study: A 26 Week, Randomized, Open Label, Parallel-group, Intention to Treat Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Diabetes
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
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2013-10-22
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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%).

Detailed 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.

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.

Primary outcomes:
measure: Mean Change From Randomization in A1c at Week 26
timeFrame: Baseline and Week 26
Secondary outcomes:
measure: Composite End-point
timeFrame: Week 0 (Randomization) , Week 26
measure: Percentage of Participants Reaching Target A1c of <7% at Week 26
timeFrame: Week 26
measure: Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome
timeFrame: week 13
measure: Mean Change From Randomization in Body Weight
timeFrame: Week 0 (Randomization) , Week 26
measure: Hypoglycemic Episodes
timeFrame: Week 0 (Randomization) , Week 2, week 4, week 13, Week 26
measure: Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
timeFrame: Week 0 (Randomization) , Week 26
measure: Change in Short Form-36 (SF-36) Questionnaire Score
timeFrame: Week 0 (Randomization) , Week 26
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Ildiko Lingvay
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patel S, Abreu M, Tumyan A, Adams-Huet B, Li X, Lingvay I. Effect of medication adherence on clinical outcomes in type 2 diabetes: analysis of the SIMPLE study. BMJ Open Diabetes Res Care. 2019 Nov 18;7(1):e000761. doi: 10.1136/bmjdrc-2019-000761. eCollection 2019.