Diabetes Mellitus, Type 2Phase 4SIMPLENCT01966978
The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study
A Phase 4 study testing Metformin, Detemir and Liraglutide in people with Diabetes Mellitus, Type 2 and Diabetes, run by University of Texas Southwestern Medical Center at 1 site in United States.
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%). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetes Mellitus, Type 2, Diabetes
- What is being tested?
- Metformin, Detemir and Liraglutide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 157 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2014to Dec 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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%).
Read the 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
- Being tested
- Metformin, Detemir, Liraglutide, Insulin Aspart
- 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
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Metformin tablets
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)
DetemirDrug
Also called Insulin Detemir subcutaneous once or twice daily
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.
LiraglutideDrug
Also called Liraglutide 6 mg/mL Subcutaneously
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 AspartDrug
Also called Insulin Aspart Subcutaneous injection one to three times daily
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
| Study group | Role | What they receive |
|---|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | Active comparator | 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 Receives: Drug: Metformin; Drug: Detemir; Drug: Insulin Aspart |
| Metformin, insulin determir, Liraglutide | Active comparator | 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) Receives: Drug: Metformin; Drug: Detemir; Drug: Liraglutide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Randomization in A1c at Week 26
Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy
Measured: Baseline and Week 26
Secondary outcomes (7)
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)
Measured: Week 0 (Randomization) , Week 26
Percentage of Participants Reaching Target A1c of <7% at Week 26
Measured: Week 26
Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome
Treatment Failure defined as A1c>10% at week 13 (visit 5)
Measured: week 13
Mean Change From Randomization in Body Weight
Change in body weight from randomization to end of study.
Measured: Week 0 (Randomization) , Week 26
Hypoglycemic Episodes
Percentage of participants experiencing any episodes of documented hypoglycemia defined as CBG reading of <70 mg/dl
Measured: Week 0 (Randomization) , Week 2, week 4, week 13, Week 26
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.
Measured: Week 0 (Randomization) , Week 26
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.
Measured: Week 0 (Randomization) , Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2013 (estimated)
- Study startNov 2014
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ildiko Lingvay, University of Texas Southwestern Medical Center
- Investigators
- Ildiko Lingvay, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01966978
- Sponsor's protocol ID
- STU 072013-030
- Acronym
- SIMPLE
- Status last verified
- Oct 2019
- First submitted
- 17 Oct 2013
- Last updated
- 22 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 31803482
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01966978
- Acronym / sponsor ID
- SIMPLE / STU 072013-030
- Conditions
- Diabetes Mellitus, Type 2, Diabetes
- Keywords
- Diabetes Mellitus, Type 2, Insulin, Insulin, Long-Acting, Insulin, Short Acting, Detemir, Liraglutide, GLP-1, Glucagon Like Peptide
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 22 Oct 2013 (estimated)
- Results
- Posted 22 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | Active comparator | Drug: Metformin, Drug: Detemir, Drug: Insulin AspartMetformin 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 | Active comparator | Drug: Metformin, Drug: Detemir, Drug: LiraglutideMetformin 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) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (17 listed)
- 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:
- Any serious or unstable medical condition as it would interfere with treatment assignment as well as outcome measurement;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: Metformin tabletsMetformin 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) | Drug | Control: Metformin, Insulin Detemir, Insulin Aspart, Metformin, insulin determir, Liraglutide |
| DetemirAlso: Insulin Detemir subcutaneous once or twice dailyInsulin 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. | Drug | Control: Metformin, Insulin Detemir, Insulin Aspart, Metformin, insulin determir, Liraglutide |
| LiraglutideAlso: Liraglutide 6 mg/mL SubcutaneouslyInitial 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 | Drug | Metformin, insulin determir, Liraglutide |
| Insulin AspartAlso: Insulin Aspart Subcutaneous injection one to three times dailyInsulin 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 | Drug | Control: Metformin, Insulin Detemir, Insulin Aspart |
Primary outcome
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
7 secondary outcomes
Composite End-point
Time frame: Week 0 (Randomization) , Week 26
Percentage of Participants Reaching Target A1c of <7% at Week 26
Time frame: Week 26
Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome
Time frame: week 13
Mean Change From Randomization in Body Weight
Time frame: Week 0 (Randomization) , Week 26
Hypoglycemic Episodes
Time frame: 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
Change in Short Form-36 (SF-36) Questionnaire Score
Time frame: Week 0 (Randomization) , Week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31803482Patel 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ildiko Lingvay principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin, Detemir and Liraglutide in people with Diabetes Mellitus, Type 2 and Diabetes, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Randomization in A1c at Week 26 (time frame: Baseline and Week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01966978, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2019.