This study will compare insulin lispro low mixture \[LM\] and insulin glargine both in combination with the patient's oral diabetes medicines, for their ability to control blood sugar in patients with type 2 diabetes and compare insulin lispro LM to insulin glargine with regard to the length of time that the overall blood sugar can be controlled. This study will also determine whether the safety of insulin lispro LM and any side effects that might be associated with it are different from those observed with insulin glargine, both in combination with the patient's oral diabetes medications. The addendum study (Intensification Addendum) will compare how different insulin treatments work to control blood sugar in patients whose diabetes could not be controlled by either insulin lispro LM or insulin glargine.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2,091
Subcutaneous injection daily
Subcutaneous injection twice daily.
Lispro Mid Mix subcutaneous injection 3 times daily.
Lispro subcutaneous injection 3 times daily.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Mobile, Alabama, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Litchfield Park, Arizona, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Little Rock, Arkansas, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Anaheim, California, United States
INITIATION: 24-Week Endpoint Glycosylated Hemoglobin (HbA1c)
Time frame: Endpoint (Initiation: Week 24)
MAINTENANCE: Duration of Time HbA1c Maintained at Goal by Initiation Regimen (Insulin Glargine or Lispro Low Mix)
HbA1c goal: HbA1c ≤7.0% or HbA1c \>7.0% but increased \<0.4% from last HbA1c ≤7.0%
Time frame: Endpoint (Last Observation Carried Forward [LOCF]) (Maintenance: up to 2.5 years)
ADDENDUM: 24-Week Endpoint HbA1c
HbA1c at 24-week endpoint in Intensification Addendum of the trial.
Time frame: Endpoint (Addendum) (24 weeks: Week 48)
INITIATION: Change in HbA1c From Baseline to 24 Weeks
Time frame: Baseline (Initiation) to Endpoint (LOCF, Week 24)
INITIATION: Percentage of Participants With HbA1c < or = 7.0%, HbA1c <7.0%, and HbA1c < or = 6.5% at Endpoint
Time frame: Endpoint (Initiation: Week 24)
INITIATION: HbA1c
Time frame: Baseline (Initiation), Week 12, Week 24, Endpoint (LOCF)
INITIATION: 7-point Self-monitored Plasma Glucose (SMPG) Profiles and Postprandial Excursions
Abbreviations: AM = morning; BG = blood glucose; PM = evening; PP = postprandial. A postprandial excursion is defined as: 2 hour postmeal plasma glucose-premeal plasma glucose.
Time frame: Endpoint (LOCF) (Initiation: Week 24)
INITIATION: Change From Baseline to Endpoint in 1,5 Anhydroglucitol (1,5 AG)
Time frame: Baseline (Initiation), Endpoint (Week 24)
INITIATION: Incremental Change From Baseline in Body Weight
Time frame: Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF)
INITIATION: Body Weight
Time frame: Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF)
INITIATION: Percentage of Participants With Self-reported Hypoglycemic Episodes
Hypoglycemia = any time participant feels/person observes that the participant is experiencing a sign/symptom they associate with hypoglycemia (such as hunger, dizziness, shakiness, light-headedness, sweating, irritability, headache, fast heart beat, confusion, etc) or a glucose measurement ≤70 mg/dL (≤3.9 mmol/L). Severe hypoglycemia = participant requires assistance. Qualified medical staff instructed the participants about the signs and symptoms of hypoglycemia.
Time frame: Baseline (Initiation), Endpoint (Week 24), Overall (sum of frequencies of hypoglycemic episodes after baseline ([Week 0]).
INITIATION: Rate of Self-reported Hypoglycemic Episodes
Hypoglycemia = participant feels/person observes, that participant is experiencing a sign/symptom they associate with hypoglycemia (such as hunger, dizziness, shakiness, light-headedness, sweating, irritability, headache, fast heart beat, confusion, etc) or glucose measurement ≤70 mg/dL (≤3.9 mmol/L). Severe hypoglycemia = participant requires assistance. Qualified medical staff instructed the participants about the signs and symptoms of hypoglycemia.
Time frame: Endpoint (Initiation: Week 24), Overall (incidence of hypoglycemic episodes after baseline [Week 0])
INITIATION: Insulin Dose
Time frame: Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, Endpoint (LOCF)
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Age
Comparison of age at baseline between those participants who met their goal at Week 24 versus those who did not meet their goal at Week 24 (goal HbA1c ≤7.0%).
Time frame: Endpoint (Initiation: Week 24)
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Origin
Comparison of origin at baseline between those participants who met their goal at Week 24 versus those who did not meet their goal at Week 24 (goal HbA1c ≤7.0%).
Time frame: Endpoint (Initiation: Week 24)
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Comparison of HOMA-IR (surrogate markers of insulin resistance calculated from fasting insulin and glucose) at baseline between those participants who met their goal at Week 24 and those who did not meet their goal at Week 24 (goal HbA1c ≤7.0%). HOMA-IR = fasting insulin (milliunits per milliliter) \* fasting plasma glucose (millimoles per liter) / 22.5.
Time frame: Endpoint (Initiation: Week 24)
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - HbA1c
Comparison of baseline HbA1c between those participants who met their goal at Week 24 versus those who did not meet their goal at Week 24 (goal HbA1c ≤7.0%).
Time frame: Endpoint (Initiation: Week 24)
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Baseline HbA1c Percentage Group
Comparison of baseline HbA1c percentage group (\<8.5,\>=8.5) between those participants who met their goal at Week 24 versus those who did not meet their goal at Week 24 (goal HbA1c ≤7.0%).
Time frame: Endpoint (Initiation: Week 24)
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - 1,5 AG
Comparison of 1,5 AG between those participants who met their goal at Week 24 versus those who did not meet their goal at Week 24 (goal HbA1c ≤7.0%).
Time frame: Endpoint (Initiation: Week 24)
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Pre Meals Blood Glucose, Post Meals Blood Glucose, Average of All Blood Glucose, and Fasting Blood Glucose
Comparison of pre meals blood glucose, post meals blood glucose, average of all blood glucose, and fasting blood glucose between those participants who met their goal at Week 24 versus those who did not meet their goal at Week 24 (goal HbA1c ≤7.0%).
Time frame: Endpoint (Initiation: Week 24)
INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal - Oral Diabetes Medication at Baseline
Comparison of oral diabetes medication at baseline between those participants who met their goal at Week 24 versus those who did not meet their goal at Week 24 (goal HbA1c ≤7.0%).
Time frame: Endpoint (Initiation: Week 24)
MAINTENANCE: HbA1c at Specified Visits and Endpoint
Time frame: Baseline (Week 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (up to 2.5 years)
MAINTENANCE: 7-point SMPG Profiles and Postprandial Excursions
Abbreviations: AM = morning; BG = blood glucose; PM = evening; PP = postprandial. A postprandial excursion is defined as: 2 hour postmeal plasma glucose-premeal plasma glucose.
Time frame: Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years)
MAINTENANCE: Rate of Increase in HbA1c
Rate of increase: HbA1c change/time period (month).
Time frame: Endpoint (LOCF) (Maintenance: up to 2.5 years)
MAINTENANCE: Percentage of Participants With HbA1c < or = 7.0%, HbA1c <7.0, and HbA1c < or = 6.5%
Time frame: Endpoint (LOCF) (Maintenance: up to 2.5 years)
MAINTENANCE: Incremental Change From Baseline in Body Weight
Time frame: Baseline (Week 0), Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Body Weight
Time frame: Baseline (Week 0), Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Insulin Dose
Time frame: Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Percentage of Participants With Self-reported Hypoglycemic Episodes
Hypoglycemia = participant feels/person observes that the participant is experiencing a sign/symptom they associate with hypoglycemia (such as hunger, dizziness, shakiness, light-headedness, sweating, irritability, headache, fast heart beat, confusion, etc) or a glucose measurement ≤70 mg/dL (≤3.9 mmol/L). Severe hypoglycemia = participant requires assistance. Qualified medical staff instructed the participants about the signs and symptoms of hypoglycemia.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years), Overall (incidence of hypoglycemic episodes after baseline (Week 0)
MAINTENANCE: Rate of Self-reported Hypoglycemic Episodes
Hypoglycemia = participant feels/person observes that the participant is experiencing a sign/symptom they associate with hypoglycemia (such as hunger, dizziness, shakiness, light-headedness, sweating, irritability, headache, fast heart beat, confusion, etc) or a glucose measurement ≤70 mg/dL (≤3.9 mmol/L). Severe hypoglycemia = participant requires assistance. Qualified medical staff instructed the participants about the signs and symptoms of hypoglycemia.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years), Overall (incidence of hypoglycemic episodes after baseline [Week 0])
MAINTENANCE: Change From Baseline in 1,5-Anhydroglucitol
Time frame: Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years)
MAINTENANCE: Change From Baseline to Endpoint in HbA1c
Time frame: Baseline (Week 0), Week 24, Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes
Comparison of duration of diabetes at baseline between those participants taking insulin glargine that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes
Comparison of duration of diabetes at baseline between those participants taking lispro LM that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes Group
Comparison of duration of diabetes group (\<10, 10-\<20, \>=20 years) at baseline between those participants taking insulin glargine that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes Group
Comparison of duration of diabetes group (\<10, 10-\<20, \>=20 years) at baseline between those participants taking Lispro LM that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c
Comparison of baseline HbA1c between those participants taking insulin glargine that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c
Comparison of baseline HbA1c between those participants taking Lispro LM that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c Group
Comparison of baseline HbA1c group (\<8.5,\>=8.5) between those participants taking insulin glargine that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c Group
Comparison of baseline HbA1c group (\<8.5,\>=8.5) between those participants taking Lispro LM that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Oral Diabetes Medicine at Baseline
Comparison of oral diabetes medication at baseline between those participants taking insulin glargine that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Oral Diabetes Medicine at Baseline
Comparison of oral diabetes medication at baseline between those participants taking Lispro LM that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - 1,5 AG
Comparison of baseline 1,5 AG between those participants taking insulin glargine that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - 1,5 AG
Comparison of baseline 1,5 AG between those participants taking Lispro LM that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Mean of Post Meals Blood Glucose and Average of All Blood Glucose
Comparison of baseline mean of post meals blood glucose and average of all blood glucose between those participants taking insulin glargine that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Mean of Post Meals Blood Glucose and Average of All Blood Glucose
Comparison of baseline mean of post meals blood glucose and average of all blood glucose between those participants taking Lispro LM that maintained their HbA1c goal and those that did not. Participants who maintained goal are those who did not fail during their duration on study. Failure is defined by HbA1c \> 7.0% with change \>= 0.4% from most recent HbA1c that was \<=7.0%.
Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)
ADDENDUM: Change in HbA1c From Point of Second Randomization (Addendum Baseline) to Endpoint
Time frame: Baseline (Addendum: Week 24), Endpoint (24 weeks [Week 48])
ADDENDUM: Percentage of Participants With HbA1c < or = 7.0%, HbA1c < 7.0%, and < or = 6.5%
Time frame: Endpoint (Addendum: 24 weeks [Week 48])
ADDENDUM: 7-point SMPG Profiles
Abbreviations: AM = morning; BG = blood glucose; PM = evening; PP = postprandial. A postprandial excursion is defined as: 2 hour postmeal plasma glucose-premeal plasma glucose.
Time frame: Endpoint (Addendum: 24 weeks [Week 48])
ADDENDUM: Incremental Change From Baseline in Body Weight
Time frame: Baseline (Addendum: Week 24), Weeks 6 (30 Weeks), 12 (36 Weeks), 24 (48 Weeks), Endpoint (LOCF)
ADDENDUM: Body Weight
Time frame: Baseline (Addendum Week 24), Weeks 6 (30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)
ADDENDUM: Insulin Dose
Time frame: Baseline (Addendum: Week 24), Weeks 1 (25 weeks), 2 (26 weeks), 3 (27 weeks), 4 (28 weeks), 5 (25 weeks), 6 (26 weeks), 8 (32 weeks), 10 (34 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)
ADDENDUM: Percentage of Participants With Self-reported Hypoglycemic Episodes
Hypoglycemia = any time participant feels/person observes, that the participant is experiencing a sign/symptom they associate with hypoglycemia (such as hunger, dizziness, shakiness, light-headedness, sweating, irritability, headache, fast heart beat, confusion, etc) or a glucose measurement ≤70 mg/dL (≤3.9 mmol/L). Severe hypoglycemia = participant requires assistance. Qualified medical staff instructed the participants about the signs and symptoms of hypoglycemia.
Time frame: Weeks 6 (Addendum: 30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)
ADDENDUM: Rate of Self-reported Hypoglycemic Episodes
Hypoglycemia = participant feels/person observes, that the participant is experiencing a sign/symptom they associate with hypoglycemia (such as hunger, dizziness, shakiness, light-headedness, sweating, irritability, headache, fast heart beat, confusion, etc) or a glucose measurement ≤70 mg/dL (≤3.9 mmol/L). Severe hypoglycemia = participant requires assistance. Qualified medical staff instructed the participants about the signs and symptoms of hypoglycemia.
Time frame: Endpoint (Addendum 24 weeks), Overall (mean yearly rate of hypoglycemia during addendum phase
ADDENDUM: Change From Baseline in 1,5-Anhydroglucitol to Week 24
Time frame: Baseline (addendum: 24 weeks), Endpoint (24 weeks: Week 48)
ADDENDUM: HbA1c at Specified Visits and Endpoint
Time frame: Baseline (Addendum: 24 weeks), Weeks 12, 24, Endpoint (24 weeks: Week 48)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Beverly Hills, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Burlingame, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Concord, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Fountain Valley, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Fresno, California, United States
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Greenbrae, California, United States
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