Primary outcomeMean· Baseline and Week 26
Mean Change From Randomization in A1c at Week 26
| Group | Value (Percentage of glycosylated hemoglobin) |
|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | 3.4 |
| Metformin, Insulin Determir, Liraglutide | 4.1 |
Trial · Interventional
CompletedPhase 4Results postedRegistry dataThe Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study
Short name SIMPLE
NCTNCT01966978 (opens ClinicalTrials.gov in a new tab)Other idSTU 072013-030
Overview
- Status
- Completed
- Phase
- Phase 4
- Enrollment
- 157 participants (actual)
- Sponsor
- University of Texas Southwestern Medical Center · Other
- Design
- Randomized · Open label (no masking)
- Countries
1 country
United States
- Start
- Nov 2014
- Primary completion
- Dec 2017
- Completion
- Dec 2017
- First posted
- 22 Oct 2013 (estimated)
- Last update posted
- 22 Oct 2019
- Conditions
- Diabetes Mellitus, Type 2 · Diabetes
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
20142015201620172018
- Ph 4
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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%).
Interventions
- MetforminDrug
- DetemirDrug
- LiraglutideDrug
- Insulin AspartDrug
Arms2
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
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)
Primary outcomes1
Outcomes the sponsor listed as primary.
Mean Change From Randomization in A1c at Week 26
Time frame · Baseline and Week 26
Registry description
Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy
Secondary outcomes(7)
Composite End-point
Time frame · Week 0 (Randomization) , Week 26
Registry 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)
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
Registry description
Treatment Failure defined as A1c\>10% at week 13 (visit 5)
Mean Change From Randomization in Body Weight
Time frame · Week 0 (Randomization) , Week 26
Registry description
Change in body weight from randomization to end of study.
Hypoglycemic Episodes
Time frame · Week 0 (Randomization) , Week 2, week 4, week 13, Week 26
Registry description
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
Time frame · Week 0 (Randomization) , Week 26
Registry description
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
Time frame · Week 0 (Randomization) , Week 26
Registry description
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.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(7)
Secondary outcomeNumber· Week 0 (Randomization) , Week 26
Composite End-point
| Group | Value (percentage of participants) |
|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | 16 |
| Metformin, Insulin Determir, Liraglutide | 34 |
Secondary outcomeNumber· Week 26
Percentage of Participants Reaching Target A1c of <7% at Week 26
| Group | Value (percentage of participants) |
|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | 20 |
| Metformin, Insulin Determir, Liraglutide | 44 |
Secondary outcomeNumber· week 13
Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome
| Group | Value (percentage of participants) |
|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | 16.1 |
| Metformin, Insulin Determir, Liraglutide | 7.4 |
Secondary outcomeMean· Week 0 (Randomization) , Week 26
Mean Change From Randomization in Body Weight
| Group | Value (kilogram) |
|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | 3.1 |
| Metformin, Insulin Determir, Liraglutide | -0.6 |
Secondary outcomeNumber· Week 0 (Randomization) , Week 2, week 4, week 13, Week 26
Hypoglycemic Episodes
| Group | Value (percentage of participants) |
|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | 66.1 |
| Metformin, Insulin Determir, Liraglutide | 35.2 |
Secondary outcomeLeast squares mean· Week 0 (Randomization) , Week 26
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
| Group | Value (score on a scale) |
|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | -0.3 |
| Metformin, Insulin Determir, Liraglutide | -0.9 |
Secondary outcomeLeast squares mean· Week 0 (Randomization) , Week 26
Change in Short Form-36 (SF-36) Questionnaire Score
| Group | Value (score on a scale) |
|---|---|
| Control: Metformin, Insulin Detemir, Insulin Aspart | -0.1 |
| Metformin, Insulin Determir, Liraglutide | 0.007 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Control: Metformin, Insulin Detemir, 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: 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. 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 | 0 / 56 | 13 / 56 | 40 / 56 |
| Metformin, Insulin Determir, 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) 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 | 0 / 54 | 6 / 54 | 50 / 54 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies1
Studies that cite this trial.
Studies with results
1 study on this page
Indexing hint: Randomized controlled trial · 2019
9 results
Effect of medication adherence on clinical outcomes in type 2 diabetes: analysis of the SIMPLE study.
Patel et al. 2019BMJ open diabetes research & carecited by 49
PMID 31803482PMC6887507DOI 10.1136/bmjdrc-2019-000761PUB-31803482
Free to read · publisher termsCC BY-NC9 results
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years up to 80 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
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.
PepBank is a research reference. Talk to a doctor before you use any peptide.