Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes

Phase 4

Completed

Conditions: Diabetes Mellitus, Type 2
Acute Myocardial Infarction

Interventions: Drug: Insulin lispro
Drug: Insulin glargine
Drug: Human insulin isophane suspension (NPH)
Drug: Human insulin isophane suspension
Drug: Human insulin 30/70

Registration Number: NCT00191282

Lead Sponsor: Eli Lilly and Company

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1116

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Insulin lispro	Postprandial: Premeal insulin lispro +/- bedtime NPH
1	Human insulin isophane suspension (NPH)	Postprandial: Premeal insulin lispro +/- bedtime NPH
2	Human insulin isophane suspension	Fasting: NPH/insulin glargine or human insulin 30/70
2	Human insulin 30/70	Fasting: NPH/insulin glargine or human insulin 30/70
2	Insulin glargine	Fasting: NPH/insulin glargine or human insulin 30/70

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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 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)
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).

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, please call 1-877-CTLILLY (1-877-285-4559, 1-317-651-4559), Monday-Friday, 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician
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Liverpool, United Kingdom