Acute Myocardial Infarction, Diabetes Mellitus, Type 2
Conditions
Keywords
diabetes, MI, heart attack
Brief summary
The primary objective was to demonstrate a difference between two insulin strategies, one targeting postprandial (PP) hyperglycemia and the other targeting fasting and interprandial hyperglycemia, on time until the first combined adjudicated cardiovascular (CV) event (primary outcome defined as CV death, nonfatal myocardial infarction \[MI\], nonfatal stroke, coronary revascularization, or hospitalized acute coronary syndrome).
Detailed description
The purpose of this study is to evaluate the effect of two different treatment strategies on CV outcomes in patients with type 2 diabetes while aiming to achieve and maintain HbA1c \<7.0% in both groups. Only patients who have recently experienced an acute MI will be considered for participation in this trial.
Interventions
DRUGInsulin lispro
Patient adjusted dose, three times a day (TID), injected subcutaneous (SC) before each meal until patient completes study
DRUGHuman insulin isophane suspension (NPH)
Patient adjusted dose, daily at bedtime, injected subcutaneous (SC) until patient completes study. To be added to the arm only if patient has two consecutive HbA1c values \>8.0%
DRUGInsulin glargine
Insulin glargine injected subcutaneous (SC) once daily in the evening until patient completes study.
DRUGHuman insulin isophane suspension
Patient adjusted dose, twice daily, injected subcutaneous (SC) before morning and evening meals until patient completes study.
Patient adjusted dose, twice daily before the morning and evening meals, injected subcutaneous (SC) until patient completes study. To replace insulin regimen in this arm only if patient has two consecutive HbA1c values \>8.0%.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Are at least 30 years old * Have had type 2 diabetes for at least 3 months prior to Visit 1 * Were admitted to the Coronary Care Unit (CCU) within 18 days prior to Visit 1 for an acute MI * Are capable and willing to do specified study procedures * Have given informed consent to participate in the study in accordance with local regulations
Exclusion criteria
* Were on one of the following therapies prior to admission to the CCU for the recent MI: a)diet therapy only and have glycosylated hemoglobin (HbA1c) \<1.15 times the upper limit of normal or b) an intensive basal/bolus insulin regimen * Are using any oral antihyperglycemic medication at the time of Visit 2 and are unwilling to stop the use of such medication for the duration of the study * Have substantial myocardial damage, which would significantly outweigh the potential benefit of the treatment strategies for diabetes * Have the most severe form of congestive heart failure * Have liver disease so severe that it precludes the patient from following and completing the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Primary Combined Outcome | Randomization (Day 0) until first occurrence of primary combined outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | The combined study outcomes consisted of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for acute coronary syndromes (HACS), and coronary revascularization procedures planned after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Death From Any Cause or Any One of the Primary Outcomes | Randomization (Day 0) until death from any cause or one of the primary outcomes (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | Primary outcomes in this study consisted of: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for acute coronary syndromes (HACS), and coronary revascularization procedure planned after randomization. |
| Number of Participants Who Experienced Any One of the Primary Outcomes Adjusted for Indicators of Metabolic Control | Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | Indicators of metabolic control included glycosylated hemoglobin (HbA1c) and fasting blood glucose concentrations. |
| Number of Participants Who Experienced Primary Outcomes Adjusted for Metabolic Control and Major Cardiovascular (CV) Risk Factors | Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | Primary outcomes adjusted for major cardiovascular (CV) risk factors (blood pressure, cholesterol \[total, high density lipoprotein (HDL), and low density lipoprotein (LDL)\], triglycerides, smoking, albuminuria, age, gender, and body mass index (BMI). |
| Number of Participants Who Experienced Death From Any Cause | Randomization (Day 0) until death from any cause (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | — |
| Number of Participants Who Experienced Cardiovascular (CV) Death | Randomization (Day 0) until cardiovascular death (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | — |
| Number of Participants Who Experienced Myocardial Infarction (MI) | Randomization (Day 0) until myocardial infarction (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | Occurrence of myocardial infarction (MI) (fatal, nonfatal, any). |
| Number of Participants Who Experienced Stroke | Randomization (Day 0) until stroke (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | Occurrence of stroke (fatal, nonfatal, any). |
| Number of Participants Who Experienced Hospitalization for Acute Coronary Syndromes (HACS) | Randomization (Day 0) until HACS (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | — |
| Number of Participants Who Experienced Coronary Revascularization Procedures | Randomization (Day 0) until coronary revascularization procedures (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | Occurrence of all coronary revascularization procedures (angioplasty or coronary artery by-pass surgery) planned after randomization. |
| Number of Participants Who Experienced Amputation for Peripheral Vascular Disease Planned After Randomization | Randomization (Day 0) until amputation (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | — |
| Number of Participants Who Experienced Congestive Heart Failure | Randomization (Day 0) until congestive heart failure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | Occurrence of congestive heart failure (newly diagnosed after Visit 2). |
| Number of Participants Who Experienced Revascularization Procedure for Peripheral Vascular Disease Planned After Randomization | Randomization (Day 0) until revascularization procedure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | — |
| Number of Participants With Self-Reported Hypoglycemia During Month 1 | Visit 3 (Month 1) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 1 | Visit 3 (Month 1) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Participants With Self-Reported Hypoglycemia During Month 3 | Visit 4 (Month 3) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 3 | Visit 4 (Month 3) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Participants With Self-Reported Hypoglycemia During Month 6 | Visit 5 (Month 6) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 6 | Visit 5 (Month 6) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Participants With Self-Reported Hypoglycemia During Month 9 | Visit 6 (Month 9) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 9 | Visit 6 (Month 9) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Participants With Self-Reported Hypoglycemia During Month 12 | Visit 7 (Month 12) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 12 | Visit 7 (Month 12) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Participants With Self-Reported Hypoglycemia During Month 18 | Visit 8 (Month 18) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 18 | Visit 8 (Month 18) | Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL). |
| Number of Participants Who Experienced Coronary Angiography Planned After Randomization | Randomization (Day 0) until coronary angiography (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) | — |
Other
| Measure | Time frame |
|---|---|
| Summary of Reasons for Deaths | Randomization (Day 0) to death (18 month initial treatment period, extended treatment follow-up period up to 5.5 years) |
Countries
Canada, Croatia, Czechia, Germany, Hungary, India, Israel, Lebanon, Poland, Romania, Russia, Slovakia, Slovenia, South Africa, Spain, Turkey (Türkiye), United Kingdom
Participant flow
Pre-assignment details
One patient was randomized but discontinued prior to treatment and is not included in any of the analyses. In the Participant Flow table, the term study outcome is used to differentiate it from serious adverse events (SAEs). By definition, the study outcomes were all SAEs as it was a cardiovascular outcome trial.
Participants by arm
| Arm | Count |
|---|---|
| Postprandial Insulin lispro: Patient adjusted dose, three times a day (TID), injected subcutaneous (SC) before each meal until patient completes study; Human insulin isophane suspension: Patient adjusted dose, daily at bedtime, injected subcutaneous (SC) until patient completes study. To be added to the arm only if patient has two consecutive HbA1c values \>8.0%. | 557 |
| Fasting Human insulin isophane suspension: injected subcutaneous (SC) twice daily before the morning and evening meals until patient completes study; Insulin glargine: injected subcutaneous (SC) once daily in the evening until patient completes study; or Human insulin 30/70: Patient adjusted dose, twice daily before the morning and evening meals, injected subcutaneous (SC) until patient completes study. To replace insulin regimen in this arm only if patient has two consecutive HbA1c values \>8.0%. | 558 |
| Total | 1,115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 |
| Overall Study | Death | 51 | 51 |
| Overall Study | Lack of Efficacy | 11 | 6 |
| Overall Study | Lost to Follow-up | 24 | 31 |
| Overall Study | Noncompliance | 14 | 17 |
| Overall Study | Patient moved | 11 | 14 |
| Overall Study | Physician Decision | 18 | 15 |
| Overall Study | Protocol entry criteria not met | 14 | 9 |
| Overall Study | Protocol Violation | 9 | 12 |
| Overall Study | Severity of outcome | 2 | 5 |
| Overall Study | Sponsor's decision | 2 | 2 |
| Overall Study | Withdrawal by Subject | 59 | 44 |
Baseline characteristics
| Characteristic | Total | Fasting | Postprandial |
|---|---|---|---|
| Age Continuous | 61.0 years STANDARD_DEVIATION 9.8 | 60.9 years STANDARD_DEVIATION 9.8 | 61.1 years STANDARD_DEVIATION 9.7 |
| Race/Ethnicity African Descent | 7 participants | 6 participants | 1 participants |
| Race/Ethnicity Caucasian | 967 participants | 483 participants | 484 participants |
| Race/Ethnicity Other | 22 participants | 11 participants | 11 participants |
| Race/Ethnicity Western Asian | 119 participants | 58 participants | 61 participants |
| Region of Enrollment Canada | 25 participants | 13 participants | 12 participants |
| Region of Enrollment Croatia | 143 participants | 71 participants | 72 participants |
| Region of Enrollment Czech Republic | 50 participants | 24 participants | 26 participants |
| Region of Enrollment Germany | 18 participants | 9 participants | 9 participants |
| Region of Enrollment Hungary | 82 participants | 41 participants | 41 participants |
| Region of Enrollment India | 70 participants | 34 participants | 36 participants |
| Region of Enrollment Israel | 76 participants | 38 participants | 38 participants |
| Region of Enrollment Lebanon | 37 participants | 19 participants | 18 participants |
| Region of Enrollment Poland | 205 participants | 103 participants | 102 participants |
| Region of Enrollment Romania | 64 participants | 31 participants | 33 participants |
| Region of Enrollment Russian Federation | 128 participants | 65 participants | 63 participants |
| Region of Enrollment Slovakia (Slovak Republic) | 19 participants | 11 participants | 8 participants |
| Region of Enrollment Slovenia | 32 participants | 16 participants | 16 participants |
| Region of Enrollment South Africa | 89 participants | 45 participants | 44 participants |
| Region of Enrollment Spain | 8 participants | 3 participants | 5 participants |
| Region of Enrollment Turkey | 36 participants | 17 participants | 19 participants |
| Region of Enrollment United Kingdom | 33 participants | 18 participants | 15 participants |
| Sex: Female, Male Female | 409 Participants | 208 Participants | 201 Participants |
| Sex: Female, Male Male | 706 Participants | 350 Participants | 356 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 356 / — | 346 / — |
| serious Total, serious adverse events | 145 / — | 142 / — |
Outcome results
Primary
Number of Participants Who Experienced a Primary Combined Outcome
The combined study outcomes consisted of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for acute coronary syndromes (HACS), and coronary revascularization procedures planned after randomization.
Time frame: Randomization (Day 0) until first occurrence of primary combined outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced a Primary Combined Outcome | 174 participants |
| Fasting | Number of Participants Who Experienced a Primary Combined Outcome | 181 participants |
Comparison: To achieve 80% power, 490 pts need to experience primary combined CV outcome to detect diff. between treatments, assuming: \>=18.5% reduction in incidence of outcomes, 18 mo. pt recruitment, 18 mo. pt follow-up, 10% annual drop-out rate, 2-yr outcome incidence rate of \>=40% (pts in least efficacious treatment), and nominal 2-sided signif. of 0.045.p-value: 0.866Log Rank
Secondary
Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 1
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 3 (Month 1)
Population: All randomized participants who self-reported hypoglycemia during Month 1.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 1 | 353 episodes of hypoglycemia |
| Fasting | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 1 | 302 episodes of hypoglycemia |
Secondary
Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 12
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 7 (Month 12)
Population: All randomized participants with self-reported hypoglycemia during Month 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 12 | 710 episodes of hypoglycemia |
| Fasting | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 12 | 486 episodes of hypoglycemia |
Secondary
Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 18
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 8 (Month 18)
Population: All randomized participants with self-reported hypoglycemia during Month 18.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 18 | 945 episodes of hypoglycemia |
| Fasting | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 18 | 669 episodes of hypoglycemia |
Secondary
Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 3
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 4 (Month 3)
Population: All randomized participants who self-reported hypoglycemia during Month 3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 3 | 567 episodes of hypoglycemia |
| Fasting | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 3 | 524 episodes of hypoglycemia |
Secondary
Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 6
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 5 (Month 6)
Population: All randomized participants with self-reported hypoglycemia during Month 6.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 6 | 770 episodes of hypoglycemia |
| Fasting | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 6 | 576 episodes of hypoglycemia |
Secondary
Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 9
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 6 (Month 9)
Population: All randomized participants with self-reported hypoglycemia during Month 9.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Postprandial | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 9 | Number of Episodes | 747 episodes of hypoglycemia |
| Fasting | Number of Episodes of Self-Reported Hypoglycemia Reported by Participants With Self-Reported Hypoglycemia During Month 9 | Number of Episodes | 569 episodes of hypoglycemia |
Secondary
Number of Participants Who Experienced Amputation for Peripheral Vascular Disease Planned After Randomization
Time frame: Randomization (Day 0) until amputation (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Amputation for Peripheral Vascular Disease Planned After Randomization | 9 participants |
| Fasting | Number of Participants Who Experienced Amputation for Peripheral Vascular Disease Planned After Randomization | 8 participants |
p-value: 0.8Log Rank
Secondary
Number of Participants Who Experienced Any One of the Primary Outcomes Adjusted for Indicators of Metabolic Control
Indicators of metabolic control included glycosylated hemoglobin (HbA1c) and fasting blood glucose concentrations.
Time frame: Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Any One of the Primary Outcomes Adjusted for Indicators of Metabolic Control | 174 participants |
| Fasting | Number of Participants Who Experienced Any One of the Primary Outcomes Adjusted for Indicators of Metabolic Control | 181 participants |
p-value: 0.914Log Rank
Secondary
Number of Participants Who Experienced Cardiovascular (CV) Death
Time frame: Randomization (Day 0) until cardiovascular death (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Cardiovascular (CV) Death | 44 participants |
| Fasting | Number of Participants Who Experienced Cardiovascular (CV) Death | 42 participants |
p-value: 0.816Log Rank
Secondary
Number of Participants Who Experienced Congestive Heart Failure
Occurrence of congestive heart failure (newly diagnosed after Visit 2).
Time frame: Randomization (Day 0) until congestive heart failure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Congestive Heart Failure | 33 participants |
| Fasting | Number of Participants Who Experienced Congestive Heart Failure | 37 participants |
p-value: 0.662Log Rank
Secondary
Number of Participants Who Experienced Coronary Angiography Planned After Randomization
Time frame: Randomization (Day 0) until coronary angiography (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Coronary Angiography Planned After Randomization | 75 participants |
| Fasting | Number of Participants Who Experienced Coronary Angiography Planned After Randomization | 86 participants |
p-value: 0.471Log Rank
Secondary
Number of Participants Who Experienced Coronary Revascularization Procedures
Occurrence of all coronary revascularization procedures (angioplasty or coronary artery by-pass surgery) planned after randomization.
Time frame: Randomization (Day 0) until coronary revascularization procedures (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Coronary Revascularization Procedures | 84 participants |
| Fasting | Number of Participants Who Experienced Coronary Revascularization Procedures | 94 participants |
p-value: 0.525Log Rank
Secondary
Number of Participants Who Experienced Death From Any Cause
Time frame: Randomization (Day 0) until death from any cause (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Death From Any Cause | 51 participants |
| Fasting | Number of Participants Who Experienced Death From Any Cause | 51 participants |
p-value: 0.982Log Rank
Secondary
Number of Participants Who Experienced Death From Any Cause or Any One of the Primary Outcomes
Primary outcomes in this study consisted of: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for acute coronary syndromes (HACS), and coronary revascularization procedure planned after randomization.
Time frame: Randomization (Day 0) until death from any cause or one of the primary outcomes (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Death From Any Cause or Any One of the Primary Outcomes | 178 participants |
| Fasting | Number of Participants Who Experienced Death From Any Cause or Any One of the Primary Outcomes | 189 participants |
p-value: 0.715Log Rank
Secondary
Number of Participants Who Experienced Hospitalization for Acute Coronary Syndromes (HACS)
Time frame: Randomization (Day 0) until HACS (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Hospitalization for Acute Coronary Syndromes (HACS) | 58 participants |
| Fasting | Number of Participants Who Experienced Hospitalization for Acute Coronary Syndromes (HACS) | 54 participants |
p-value: 0.647Log Rank
Secondary
Number of Participants Who Experienced Myocardial Infarction (MI)
Occurrence of myocardial infarction (MI) (fatal, nonfatal, any).
Time frame: Randomization (Day 0) until myocardial infarction (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Myocardial Infarction (MI) | 63 participants |
| Fasting | Number of Participants Who Experienced Myocardial Infarction (MI) | 63 participants |
p-value: 0.948Log Rank
Secondary
Number of Participants Who Experienced Primary Outcomes Adjusted for Metabolic Control and Major Cardiovascular (CV) Risk Factors
Primary outcomes adjusted for major cardiovascular (CV) risk factors (blood pressure, cholesterol \[total, high density lipoprotein (HDL), and low density lipoprotein (LDL)\], triglycerides, smoking, albuminuria, age, gender, and body mass index (BMI).
Time frame: Randomization (Day 0) until occurrence of primary outcome (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Primary Outcomes Adjusted for Metabolic Control and Major Cardiovascular (CV) Risk Factors | 174 participants |
| Fasting | Number of Participants Who Experienced Primary Outcomes Adjusted for Metabolic Control and Major Cardiovascular (CV) Risk Factors | 181 participants |
p-value: 0.706Log Rank
Secondary
Number of Participants Who Experienced Revascularization Procedure for Peripheral Vascular Disease Planned After Randomization
Time frame: Randomization (Day 0) until revascularization procedure (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Revascularization Procedure for Peripheral Vascular Disease Planned After Randomization | 11 participants |
| Fasting | Number of Participants Who Experienced Revascularization Procedure for Peripheral Vascular Disease Planned After Randomization | 12 participants |
p-value: 0.863Log Rank
Secondary
Number of Participants Who Experienced Stroke
Occurrence of stroke (fatal, nonfatal, any).
Time frame: Randomization (Day 0) until stroke (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants Who Experienced Stroke | 20 participants |
| Fasting | Number of Participants Who Experienced Stroke | 17 participants |
p-value: 0.581Log Rank
Secondary
Number of Participants With Self-Reported Hypoglycemia During Month 1
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 3 (Month 1)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants With Self-Reported Hypoglycemia During Month 1 | 124 participants |
| Fasting | Number of Participants With Self-Reported Hypoglycemia During Month 1 | 119 participants |
p-value: 0.7168Chi-squared
Secondary
Number of Participants With Self-Reported Hypoglycemia During Month 12
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 7 (Month 12)
Population: All randomized patients who took at least one dose of study drug and who were still in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants With Self-Reported Hypoglycemia During Month 12 | 146 participants |
| Fasting | Number of Participants With Self-Reported Hypoglycemia During Month 12 | 130 participants |
p-value: 0.2434Chi-squared
Secondary
Number of Participants With Self-Reported Hypoglycemia During Month 18
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 8 (Month 18)
Population: All randomized patients who took at least one dose of study drug and who were still in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants With Self-Reported Hypoglycemia During Month 18 | 143 participants |
| Fasting | Number of Participants With Self-Reported Hypoglycemia During Month 18 | 129 participants |
p-value: 0.2617Chi-squared
Secondary
Number of Participants With Self-Reported Hypoglycemia During Month 3
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 4 (Month 3)
Population: All randomized patients who took at least one dose of study drug and who were still in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants With Self-Reported Hypoglycemia During Month 3 | 160 participants |
| Fasting | Number of Participants With Self-Reported Hypoglycemia During Month 3 | 139 participants |
p-value: 0.086Chi-squared
Secondary
Number of Participants With Self-Reported Hypoglycemia During Month 6
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 5 (Month 6)
Population: All randomized patients who took at least one dose of study drug and who were still in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants With Self-Reported Hypoglycemia During Month 6 | 163 participants |
| Fasting | Number of Participants With Self-Reported Hypoglycemia During Month 6 | 145 participants |
p-value: 0.1424Chi-squared
Secondary
Number of Participants With Self-Reported Hypoglycemia During Month 9
Hypoglycemia was defined as any time a patient feels, or another person observes, that the patient is experiencing a sign/symptom which he/she would associate with hypoglycemia (for example, tremors, headache, sweating, disorientation, weakness, etc) or a blood glucose measurement less than 3.5 mmol/L (63 mg/dL).
Time frame: Visit 6 (Month 9)
Population: All randomized patients who took at least one dose of study drug and who were still in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Postprandial | Number of Participants With Self-Reported Hypoglycemia During Month 9 | 155 participants |
| Fasting | Number of Participants With Self-Reported Hypoglycemia During Month 9 | 138 participants |
p-value: 0.1957Chi-squared
Other Pre-specified
Summary of Reasons for Deaths
Time frame: Randomization (Day 0) to death (18 month initial treatment period, extended treatment follow-up period up to 5.5 years)
Population: All randomized patients who took at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Postprandial | Summary of Reasons for Deaths | Fatal Stroke | 3 participants |
| Postprandial | Summary of Reasons for Deaths | Non-CV Death | 7 participants |
| Postprandial | Summary of Reasons for Deaths | CV Death other than Stroke/MI | 29 participants |
| Postprandial | Summary of Reasons for Deaths | Unknown | 0 participants |
| Postprandial | Summary of Reasons for Deaths | Fatal MI | 12 participants |
| Fasting | Summary of Reasons for Deaths | Unknown | 1 participants |
| Fasting | Summary of Reasons for Deaths | Fatal MI | 12 participants |
| Fasting | Summary of Reasons for Deaths | Fatal Stroke | 2 participants |
| Fasting | Summary of Reasons for Deaths | CV Death other than Stroke/MI | 28 participants |
| Fasting | Summary of Reasons for Deaths | Non-CV Death | 8 participants |