The Durability of Twice-Daily Insulin Lispro Low Mixture Compared to Once-Daily Insulin Glargine When Added to Existing Oral Therapy in Patients With Type 2 Diabetes and Inadequate Glycemic Control
Overview
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 2,091
- Locations
- 1
- Primary Endpoint
- INITIATION: 24-Week Endpoint Glycosylated Hemoglobin (HbA1c)
Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 30 Years to 79 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Must have type 2 diabetes.
- •Must be at least 30 and less than 80 years of age at the time of Visit
- •Must be on at least two oral antidiabetes medications for at least 90 days.
- •Must have an HbA1c 1.2 to 2.0 times the upper limit of normal reference range at the local lab.
Exclusion Criteria
- •Must not have used insulin on a regular basis in the last 12 months.
- •Must not have had more than one episode of severe hypoglycemia in the last 24 weeks.
- •Must not have a body mass index (BMI) of greater than 45 (morbid obesity).
- •Must not have clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease.
- •Must not be pregnant or intend to get pregnant during course of the study.
Arms & Interventions
Insulin glargine
Initiation Phase: Insulin glargine for 24 weeks Maintenance: Up to an additional 2 years of insulin glargine if glycosylated hemoglobin (HbA1c) less than or equal to 7.0 at 24 weeks.
Intervention: Insulin glargine (Drug)
Lispro Low Mix
Initiation Phase: Lispro Low Mix (LM) for 24 weeks Maintenance Phase: Up to an additional 2 years of Lispro LM if HbA1c less than or equal to 7.0 at 24 weeks.
Intervention: Lispro Low Mix (Drug)
Lispro Mid Mix prior Lispro Low Mix addendum
Following Lispro LM Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Lispro Mid Mix for 24 weeks in the Intensification Addendum Phase.
Intervention: Lispro Mid Mix (Drug)
Lispro Low Mix prior Glargine addendum
Following Insulin Glargine Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Lispro Low Mix for 24 weeks in the Intensification Addendum Phase
Intervention: Lispro Low Mix (Drug)
Basal bolus prior Lispro Low Mix addendum
Following Lispro LM Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Basal Bolus therapy (combination of insulin glargine and lispro) for 24 weeks in the Intensification Addendum Phase.
Intervention: Insulin glargine (Drug)
Basal bolus prior Lispro Low Mix addendum
Following Lispro LM Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Basal Bolus therapy (combination of insulin glargine and lispro) for 24 weeks in the Intensification Addendum Phase.
Intervention: Lispro (Drug)
Basal bolus prior Glargine addendum
Following Insulin Glargine Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Basal Bolus therapy (combination of insulin glargine and lispro) for 24 weeks in the Intensification Addendum Phase.
Intervention: Insulin glargine (Drug)
Basal bolus prior Glargine addendum
Following Insulin Glargine Initiation Phase, if HbA1c greater than 7.0 after 24 weeks, then instead of entering Maintenance Phase, participants could be randomized to receive Basal Bolus therapy (combination of insulin glargine and lispro) for 24 weeks in the Intensification Addendum Phase.
Intervention: Lispro (Drug)
Outcomes
Primary Outcomes
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)
Time Frame: Endpoint (Last Observation Carried Forward [LOCF]) (Maintenance: up to 2.5 years)
HbA1c goal: HbA1c ≤7.0% or HbA1c \>7.0% but increased \<0.4% from last HbA1c ≤7.0%
ADDENDUM: 24-Week Endpoint HbA1c
Time Frame: Endpoint (Addendum) (24 weeks: Week 48)
HbA1c at 24-week endpoint in Intensification Addendum of the trial.
Secondary Outcomes
- INITIATION: Change in HbA1c From Baseline to 24 Weeks(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(Endpoint (Initiation: Week 24))
- INITIATION: HbA1c(Baseline (Initiation), Week 12, Week 24, Endpoint (LOCF))
- INITIATION: 7-point Self-monitored Plasma Glucose (SMPG) Profiles and Postprandial Excursions(Endpoint (LOCF) (Initiation: Week 24))
- INITIATION: Change From Baseline to Endpoint in 1,5 Anhydroglucitol (1,5 AG)(Baseline (Initiation), Endpoint (Week 24))
- INITIATION: Incremental Change From Baseline in Body Weight(Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF))
- INITIATION: Body Weight(Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF))
- INITIATION: Percentage of Participants With Self-reported Hypoglycemic Episodes(Baseline (Initiation), Endpoint (Week 24), Overall (sum of frequencies of hypoglycemic episodes after baseline ([Week 0]).)
- INITIATION: Rate of Self-reported Hypoglycemic Episodes(Endpoint (Initiation: Week 24), Overall (incidence of hypoglycemic episodes after baseline [Week 0]))
- INITIATION: Insulin Dose(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(Endpoint (Initiation: Week 24))
- INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Origin(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)(Endpoint (Initiation: Week 24))
- INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - HbA1c(Endpoint (Initiation: Week 24))
- INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Baseline HbA1c Percentage Group(Endpoint (Initiation: Week 24))
- INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - 1,5 AG(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(Endpoint (Initiation: Week 24))
- INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal - Oral Diabetes Medication at Baseline(Endpoint (Initiation: Week 24))
- MAINTENANCE: HbA1c at Specified Visits and Endpoint(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(Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years))
- MAINTENANCE: Rate of Increase in HbA1c(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%(Endpoint (LOCF) (Maintenance: up to 2.5 years))
- MAINTENANCE: Incremental Change From Baseline in Body Weight(Baseline (Week 0), Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years))
- MAINTENANCE: Body Weight(Baseline (Week 0), Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years))
- MAINTENANCE: Insulin Dose(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(Endpoint (LOCF) (Maintenance) (up to 2.5 years), Overall (incidence of hypoglycemic episodes after baseline (Week 0))
- MAINTENANCE: Rate of Self-reported Hypoglycemic Episodes(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(Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years))
- MAINTENANCE: Change From Baseline to Endpoint in HbA1c(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(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(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(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(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(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(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(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(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(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(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(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(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(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(Endpoint (LOCF) (Maintenance) (up to 2.5 years))
- ADDENDUM: Change in HbA1c From Point of Second Randomization (Addendum Baseline) to Endpoint(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%(Endpoint (Addendum: 24 weeks [Week 48]))
- ADDENDUM: 7-point SMPG Profiles(Endpoint (Addendum: 24 weeks [Week 48]))
- ADDENDUM: Incremental Change From Baseline in Body Weight(Baseline (Addendum: Week 24), Weeks 6 (30 Weeks), 12 (36 Weeks), 24 (48 Weeks), Endpoint (LOCF))
- ADDENDUM: Body Weight(Baseline (Addendum Week 24), Weeks 6 (30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF))
- ADDENDUM: Insulin Dose(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(Weeks 6 (Addendum: 30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF))
- ADDENDUM: Rate of Self-reported Hypoglycemic Episodes(Endpoint (Addendum 24 weeks), Overall (mean yearly rate of hypoglycemia during addendum phase)
- ADDENDUM: Change From Baseline in 1,5-Anhydroglucitol to Week 24(Baseline (addendum: 24 weeks), Endpoint (24 weeks: Week 48))
- ADDENDUM: HbA1c at Specified Visits and Endpoint(Baseline (Addendum: 24 weeks), Weeks 12, 24, Endpoint (24 weeks: Week 48))