Trial Outcomes & Findings for The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study (NCT NCT01966978)
NCT ID: NCT01966978
Last Updated: 2019-10-22
Results Overview
Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
157 participants
Primary outcome timeframe
Baseline and Week 26
Results posted on
2019-10-22
Participant Flow
Total number of subjects consented is 157, total number of subjects randomized is 120, of those 120 only 110 are MITT data set
Participant milestones
| Measure |
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
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
|
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)
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
|
|---|---|---|
|
Overall Study
STARTED
|
61
|
59
|
|
Overall Study
COMPLETED
|
44
|
46
|
|
Overall Study
NOT COMPLETED
|
17
|
13
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Effect of Simple Basal Insulin Titration, Metformin Plus Liraglutide for Type 2 Diabetes With Very Elevated HbA1c - The SIMPLE Study
Baseline characteristics by cohort
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=61 Participants
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=59 Participants
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)
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
|
Total
n=120 Participants
Total of all reporting groups
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|---|---|---|---|
|
Age, Continuous
|
48.1 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
46.7 years
STANDARD_DEVIATION 9.0 • n=7 Participants
|
47.4 years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
85 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
21 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic White
|
10 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African-American
|
30 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
HbA1c
|
12.0 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.5 • n=5 Participants
|
12.1 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.4 • n=7 Participants
|
12.1 percentage of glycosylated hemoglobin
STANDARD_DEVIATION 1.4 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 26Change in glycosylated Hemoglobin A1c (A1c) from randomization to 26 weeks of therapy
Outcome measures
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=44 Participants
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=46 Participants
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)
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
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|---|---|---|
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Mean Change From Randomization in A1c at Week 26
|
3.4 Percentage of glycosylated hemoglobin
Interval 2.4 to 3.7
|
4.1 Percentage of glycosylated hemoglobin
Interval 3.5 to 4.8
|
SECONDARY outcome
Timeframe: Week 0 (Randomization) , Week 26Percentage 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)
Outcome measures
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=44 Participants
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=46 Participants
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)
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
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|---|---|---|
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Composite End-point
|
16 percentage of participants
|
34 percentage of participants
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SECONDARY outcome
Timeframe: Week 26Outcome measures
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=44 Participants
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=46 Participants
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)
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
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|---|---|---|
|
Percentage of Participants Reaching Target A1c of <7% at Week 26
|
20 percentage of participants
|
44 percentage of participants
|
SECONDARY outcome
Timeframe: week 13Treatment Failure defined as A1c\>10% at week 13 (visit 5)
Outcome measures
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=44 Participants
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=46 Participants
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)
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
|
|---|---|---|
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Percentage of Participants Reaching Pre-specified "Treatment Failure" Outcome
|
16.1 percentage of participants
|
7.4 percentage of participants
|
SECONDARY outcome
Timeframe: Week 0 (Randomization) , Week 26Change in body weight from randomization to end of study.
Outcome measures
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=44 Participants
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=46 Participants
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)
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
|
|---|---|---|
|
Mean Change From Randomization in Body Weight
|
3.1 kilogram
Interval 1.7 to 4.6
|
-0.6 kilogram
Interval -0.9 to 2.1
|
SECONDARY outcome
Timeframe: Week 0 (Randomization) , Week 2, week 4, week 13, Week 26Percentage of participants experiencing any episodes of documented hypoglycemia defined as CBG reading of \<70 mg/dl
Outcome measures
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=44 Participants
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=46 Participants
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)
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
|
|---|---|---|
|
Hypoglycemic Episodes
|
66.1 percentage of participants
|
35.2 percentage of participants
|
SECONDARY outcome
Timeframe: Week 0 (Randomization) , Week 26Diabetes 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.
Outcome measures
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=44 Participants
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=46 Participants
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)
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
|
|---|---|---|
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Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
General Health Perception
|
-0.3 score on a scale
Interval -0.6 to -0.1
|
-0.9 score on a scale
Interval -1.1 to -0.6
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Current Health Perception
|
-0.5 score on a scale
Interval -0.9 to -0.1
|
-1.1 score on a scale
Interval -1.5 to -0.7
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Treatment Satisfaction
|
-0.3 score on a scale
Interval -0.5 to -0.04
|
-0.6 score on a scale
Interval -0.8 to -0.4
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Diabetes Related Worry
|
0.03 score on a scale
Interval -0.1 to 0.2
|
-0.2 score on a scale
Interval -0.4 to -0.04
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Social or Vocational Worry
|
-0.02 score on a scale
Interval -0.3 to 0.3
|
-0.2 score on a scale
Interval -0.4 to 0.08
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Hypoglycemia Fear
|
0.3 score on a scale
Interval 0.04 to 0.5
|
-0.2 score on a scale
Interval -0.4 to -0.005
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Glycemic Control Perception
|
-1.1 score on a scale
Interval -1.6 to -0.7
|
-1.6 score on a scale
Interval -2.0 to -1.2
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Satisfaction with Insulin Treatment
|
-1.3 score on a scale
Interval -1.8 to -0.8
|
-1.7 score on a scale
Interval -2.2 to -1.2
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Willingness to Continue Insulin Treatment
|
-0.9 score on a scale
Interval -1.4 to -0.3
|
-1.1 score on a scale
Interval -1.7 to -0.6
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
LifeStyle Flexibility
|
-0.09 score on a scale
Interval -0.4 to 0.2
|
-0.2 score on a scale
Interval -0.4 to 0.1
|
|
Change in Diabetes Quality of Life (DQOL)Questionnaire Score- Least Squares Means
Social Stigma
|
0.1 score on a scale
Interval -0.2 to 0.4
|
0.01 score on a scale
Interval -0.3 to 0.4
|
SECONDARY outcome
Timeframe: Week 0 (Randomization) , Week 26Quality 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.
Outcome measures
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=44 Participants
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=46 Participants
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)
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
|
|---|---|---|
|
Change in Short Form-36 (SF-36) Questionnaire Score
Physical Component Summary
|
-0.1 score on a scale
Interval -0.4 to 0.2
|
0.007 score on a scale
Interval -0.3 to 0.3
|
|
Change in Short Form-36 (SF-36) Questionnaire Score
Mental Component Summary
|
0.04 score on a scale
Interval -0.1 to 0.1
|
0.09 score on a scale
Interval -0.02 to 0.2
|
Adverse Events
Control: Metformin, Insulin Detemir, Insulin Aspart
Serious events: 13 serious events
Other events: 40 other events
Deaths: 0 deaths
Metformin, Insulin Determir, Liraglutide
Serious events: 6 serious events
Other events: 50 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=56 participants at risk
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=54 participants at risk
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)
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
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
3.6%
2/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Skin and subcutaneous tissue disorders
Facial Burn
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Renal and urinary disorders
Urinary Tract Infection
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
3.6%
2/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.00%
0/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
1.9%
1/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Gastrointestinal disorders
Small Bowel Obstruction
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Investigations
Fall
|
3.6%
2/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Cardiac disorders
chest pain
|
0.00%
0/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
1.9%
1/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Endocrine disorders
Diabetic Ketoacidosis
|
7.1%
4/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Musculoskeletal and connective tissue disorders
Osteomyelitis
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Cardiac disorders
hypertension
|
0.00%
0/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
1.9%
1/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Cardiac disorders
myocardial infarction
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
1.9%
1/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
nasopharyngeal carcinoma
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Psychiatric disorders
psychiatric inpatient hospitalization
|
0.00%
0/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
1.9%
1/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Eye disorders
vitreal hemmorhage
|
0.00%
0/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
1.9%
1/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Infections and infestations
bacteremia
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Injury, poisoning and procedural complications
puncture wound
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Renal and urinary disorders
nephrotic syndrome
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Gastrointestinal disorders
Lower GI bleed
|
1.8%
1/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
0.00%
0/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Eye disorders
glaucoma
|
0.00%
0/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
1.9%
1/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
Other adverse events
| Measure |
Control: Metformin, Insulin Detemir, Insulin Aspart
n=56 participants at risk
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: 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
|
Metformin, Insulin Determir, Liraglutide
n=54 participants at risk
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)
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
|
|---|---|---|
|
Nervous system disorders
headache
|
17.9%
10/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
25.9%
14/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Gastrointestinal disorders
GI
|
50.0%
28/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
77.8%
42/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
|
Investigations
Other AE
|
16.1%
9/56 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
7.4%
4/54 • 6 months (Baseline to Week 26)
Adverse events were collected both by self-report as well as review of the electronic health record. Nausea, vomiting, headache, diarrhea and abdominal pain were pre-defined events of special interest and proactively elicited at each visit from all patients.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place