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

NCT ID: NCT01966978

Last Updated: 2019-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 157 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2017-12-31

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.

Conditions

Diabetes Mellitus, Type 2; Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control: Metformin, Insulin Detemir, 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

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Insulin Aspart

Intervention Type: DRUG

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

Metformin, insulin determir, 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)

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Interventions

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)

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Metformin tablets; Insulin Detemir subcutaneous once or twice daily; Liraglutide 6 mg/mL Subcutaneously; Insulin Aspart Subcutaneous injection one to three times daily

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ildiko Lingvay

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ildiko Lingvay

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31803482 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STU 072013-030

Identifier Type: -

Identifier Source: org_study_id