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

Primary Purpose

Diabetes Mellitus, Type 2, Diabetes

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Metformin

Detemir

Liraglutide

Insulin Aspart

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Diabetes Mellitus, Type 2, Insulin, Insulin, Long-Acting, Insulin, Short Acting, Detemir, Liraglutide, GLP-1, Glucagon Like Peptide, Metformin, Uncontrolled Diabetes, Elevated A1c, Incretins

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

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;
Type 1 diabetes as purposefully withholding meal-time insulin is contraindicated;
Clinical state requiring inpatient admission/treatment;
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)
Any serious or unstable medical condition as it would interfere with treatment assignment as well as outcome measurement;
Any scheduled elective procedures/surgeries;
Active infections, including osteomyelitis;
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
Non English speaking.

Sites / Locations

UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Control: Metformin, Insulin Detemir, Insulin Aspart

Metformin, insulin determir, Liraglutide

Arm Description

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 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)

Outcomes

Primary Outcome Measures

Mean Change From Randomization in A1c at Week 26

Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy

Secondary Outcome Measures

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)

Percentage of Participants Reaching Target A1c of <7% at Week 26

Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome

Treatment Failure defined as A1c>10% at week 13 (visit 5)

Mean Change From Randomization in Body Weight

Change in body weight from randomization to end of study.

Hypoglycemic Episodes

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

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.

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.

Full Information

NCT ID

NCT01966978

First Posted

October 17, 2013

Last Updated

October 1, 2019

Sponsor

University of Texas Southwestern Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01966978

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

November 2014 (undefined)

Primary Completion Date

December 2017 (Actual)

Study Completion Date

December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Texas Southwestern Medical Center

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

157 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Control: Metformin, Insulin Detemir, Insulin Aspart

Arm Type

Active Comparator

Arm Description

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

Arm Title

Metformin, insulin determir, Liraglutide

Arm Type

Active Comparator

Arm Description

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)

Intervention Type

Drug

Intervention Name(s)

Metformin

Other Intervention Name(s)

Metformin tablets

Intervention Description

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

Intervention Name(s)

Detemir

Other Intervention Name(s)

Insulin Detemir subcutaneous once or twice daily

Intervention Description

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

Intervention Name(s)

Liraglutide

Other Intervention Name(s)

Liraglutide 6 mg/mL Subcutaneously

Intervention Description

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

Intervention Name(s)

Insulin Aspart

Other Intervention Name(s)

Insulin Aspart Subcutaneous injection one to three times daily

Intervention Description

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

Primary Outcome Measure Information:

Title

Mean Change From Randomization in A1c at Week 26

Description

Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy

Time Frame

Baseline and Week 26

Secondary Outcome Measure Information:

Title

Composite End-point

Description

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)

Time Frame

Week 0 (Randomization) , Week 26

Title

Percentage of Participants Reaching Target A1c of <7% at Week 26

Time Frame

Week 26

Title

Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome

Description

Treatment Failure defined as A1c>10% at week 13 (visit 5)

Time Frame

week 13

Title

Mean Change From Randomization in Body Weight

Description

Change in body weight from randomization to end of study.

Time Frame

Week 0 (Randomization) , Week 26

Title

Hypoglycemic Episodes

Description

Percentage of participants experiencing any episodes of documented hypoglycemia defined as CBG reading of <70 mg/dl

Time Frame

Week 0 (Randomization) , Week 2, week 4, week 13, Week 26

Title

Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means

Description

Time Frame

Week 0 (Randomization) , Week 26

Title

Change in Short Form-36 (SF-36) Questionnaire Score

Description

Time Frame

Week 0 (Randomization) , Week 26

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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: 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; Type 1 diabetes as purposefully withholding meal-time insulin is contraindicated; Clinical state requiring inpatient admission/treatment; Contraindication or strong cautions to any of the study medications: Creatinine above 1.4 mg/dl for women and 1.5 mg/dl for men (per metformin label) History of lactic acidosis (per metformin label) Advanced hepatic or cardiac disease (per metformin label) Age >80 years (per metformin label) Chronic alcohol use (>14 drinks/week) History of pancreatitis (per liraglutide label) Personal or family history of medullary thyroid cancer or MEN syndrome (per liraglutide label) Pregnancy and lactation (per liraglutide label) Any serious or unstable medical condition as it would interfere with treatment assignment as well as outcome measurement; Any scheduled elective procedures/surgeries; Active infections, including osteomyelitis; 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 Non English speaking.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ildiko Lingvay

Organizational Affiliation

UT Southwestern Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UT Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

02720

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31803482

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.

Results Reference

derived

Learn more about this trial

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

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