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

Diabetes Mellitus, Type 2 Clinical Trial

— SIMPLE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01966978
• Other study ID #: STU 072013-030
• Status: Completed
• Phase: Phase 4
• Start date: November 2014
• Est. completion date: December 2017

Study information

• Verified date: October 2019
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Metformin
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)
• Detemir
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.
• Liraglutide
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
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

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Randomization in A1c at Week 26	Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy	Baseline and Week 26
Secondary	Composite End-point	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)	Week 0 (Randomization) , Week 26
Secondary	Percentage of Participants Reaching Target A1c of <7% at Week 26		Week 26
Secondary	Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome	Treatment Failure defined as A1c>10% at week 13 (visit 5)	week 13
Secondary	Mean Change From Randomization in Body Weight	Change in body weight from randomization to end of study.	Week 0 (Randomization) , Week 26
Secondary	Hypoglycemic Episodes	Percentage of participants experiencing any episodes of documented hypoglycemia defined as CBG reading of <70 mg/dl	Week 0 (Randomization) , Week 2, week 4, week 13, Week 26
Secondary	Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means	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.	Week 0 (Randomization) , Week 26
Secondary	Change in Short Form-36 (SF-36) Questionnaire Score	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.	Week 0 (Randomization) , Week 26