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

October 1, 2019 updated by: Ildiko Lingvay, University of Texas Southwestern Medical Center

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

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%).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

157

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 02720
        • UT Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: 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
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)
Other Names:
  • Metformin tablets
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.
Other Names:
  • Insulin Detemir subcutaneous once or twice daily
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
Other Names:
  • Insulin Aspart Subcutaneous injection one to three times daily
ACTIVE_COMPARATOR: 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)
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)
Other Names:
  • Metformin tablets
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.
Other Names:
  • Insulin Detemir subcutaneous once or twice daily
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
Other Names:
  • Liraglutide 6 mg/mL Subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change From Randomization in A1c at Week 26
Time Frame: Baseline and Week 26
Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy
Baseline and Week 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite End-point
Time Frame: 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)
Week 0 (Randomization) , Week 26
Percentage of Participants Reaching Target A1c of <7% at Week 26
Time Frame: Week 26
Week 26
Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome
Time Frame: week 13
Treatment Failure defined as A1c>10% at week 13 (visit 5)
week 13
Mean Change From Randomization in Body Weight
Time Frame: Week 0 (Randomization) , Week 26
Change in body weight from randomization to end of study.
Week 0 (Randomization) , Week 26
Hypoglycemic Episodes
Time Frame: 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
Week 0 (Randomization) , Week 2, week 4, week 13, Week 26
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Time Frame: 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.
Week 0 (Randomization) , Week 26
Change in Short Form-36 (SF-36) Questionnaire Score
Time Frame: 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.
Week 0 (Randomization) , Week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Investigators

  • Principal Investigator: Ildiko Lingvay, UT Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (ACTUAL)

December 1, 2017

Study Completion (ACTUAL)

December 1, 2017

Study Registration Dates

First Submitted

October 17, 2013

First Submitted That Met QC Criteria

October 21, 2013

First Posted (ESTIMATE)

October 22, 2013

Study Record Updates

Last Update Posted (ACTUAL)

October 22, 2019

Last Update Submitted That Met QC Criteria

October 1, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU 072013-030

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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