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

Phase 4

Completed

• Conditions: Diabetes; Diabetes Mellitus, Type 2
• Interventions: Drug: Metformin; Drug: Detemir; Drug: Insulin Aspart; Drug: Liraglutide

• Registration Number: NCT01966978
• Lead Sponsor: University of Texas Southwestern Medical Center

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.

Study Timeline

• Study First Submitted: 2013-10-17
• Study First Submitted QC: 2013-10-21
• Study First Posted: 2013-10-22
• Study Start: 2014-11
• Primary Completion: 2017-12
• Study Completion: 2017-12
• Results First Submitted: 2019-08-12
• Status Verified: 2019-10
• Results First Submitted QC: 2019-10-01
• Last Update Submitted: 2019-10-01
• Results First Posted: 2019-10-22
• Last Update Posted: 2019-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 157

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control: Metformin, Insulin Detemir, Insulin Aspart	Metformin	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
Control: Metformin, Insulin Detemir, Insulin Aspart	Insulin Aspart	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
Control: Metformin, Insulin Detemir, Insulin Aspart	Detemir	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
Metformin, insulin determir, Liraglutide	Metformin	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)
Metformin, insulin determir, Liraglutide	Detemir	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)
Metformin, insulin determir, Liraglutide	Liraglutide	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)

Primary Outcome Measures

Name	Time	Method
Mean Change From Randomization in A1c at Week 26	Baseline and Week 26	Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy

Secondary Outcome Measures

Name	Time	Method
Mean Change From Randomization in Body Weight	Week 0 (Randomization) , Week 26	Change in body weight from randomization to end of study.
Composite End-point	Week 0 (Randomization) , Week 26	Percentage of participants with glycosylated Hemoglobin A1c (A1c)\<8% AND no documented severe hypoglycemia (\<56 mg/dL) during the study AND no significant weight gain (\>3% from baseline)
Percentage of Participants Reaching Target A1c of <7% at Week 26	Week 26
Change in Short Form-36 (SF-36) Questionnaire Score	Week 0 (Randomization) , Week 26	Quality of life questionnaires will be completed by the patient at the randomization and end-of study visits. SF-36 is scored on a 1-100 scale; a higher score represents a better self-assessed health - for all domains.
Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome	week 13	Treatment Failure defined as A1c\>10% at week 13 (visit 5)
Hypoglycemic Episodes	Week 0 (Randomization) , Week 2, week 4, week 13, Week 26	Percentage of participants experiencing any episodes of documented hypoglycemia defined as CBG reading of \<70 mg/dl
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means	Week 0 (Randomization) , Week 26	Diabetes Quality of Life (DQOL) questionnaires will be completed by the patient at the randomization and end-of study visits. ALL D-QOL domains are scored on a 1-5 scale, with a lower number representing better quality of life or treatment satisfaction. Outcome reported is difference between mean baseline and mean Week 26 score.

Trial Locations

Locations (1)

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States