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Completed

NCT Number: NCT00279201

The DURABLE Trial: Evaluating the Durability of Starter Insulin Regimens in Patients With Type 2 Diabetes (IOOV)

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.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

30 year–79 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

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., Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Must have type 2 diabetes.
  • Must be at least 30 and less than 80 years of age at the time of Visit 1.
  • 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.

Treatment and study plan

insulin glargine

Drug

Subcutaneous injection daily

Other names: Lantus

Lispro Low Mix

Drug

Subcutaneous injection twice daily.

Other names: Humalog Mix 75/25

Lispro Mid Mix

Drug

Lispro Mid Mix subcutaneous injection 3 times daily.

Other names: Humalog Mix 50/50

Lispro

Drug

Lispro subcutaneous injection 3 times daily.

Other names: Humalog

Primary outcomes

  1. INITIATION: 24-Week Endpoint Glycosylated Hemoglobin (HbA1c)

    Time frame: Endpoint (Initiation: Week 24)

  2. 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%

  3. 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

  1. INITIATION: Change in HbA1c From Baseline to 24 Weeks

    Time frame: Baseline (Initiation) to Endpoint (LOCF, Week 24)

  2. 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)

  3. INITIATION: HbA1c

    Time frame: Baseline (Initiation), Week 12, Week 24, Endpoint (LOCF)

  4. INITIATION: 7-point Self-monitored Plasma Glucose (SMPG) Profiles and Postprandial Excursions

    Time frame: Endpoint (LOCF) (Initiation: Week 24)

    Abbreviations: AM = morning; BG = blood glucose; PM = evening; PP = postprandial. A postprandial excursion is defined as: 2 hour postmeal plasma glucose-premeal plasma glucose.

  5. INITIATION: Change From Baseline to Endpoint in 1,5 Anhydroglucitol (1,5 AG)

    Time frame: Baseline (Initiation), Endpoint (Week 24)

  6. INITIATION: Incremental Change From Baseline in Body Weight

    Time frame: Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF)

  7. INITIATION: Body Weight

    Time frame: Baseline (Initiation), Weeks 6, 12, 18, 24, Endpoint (LOCF)

  8. INITIATION: Percentage of Participants With Self-reported Hypoglycemic Episodes

    Time frame: Baseline (Initiation), Endpoint (Week 24), Overall (sum of frequencies of hypoglycemic episodes after baseline ([Week 0]).

    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.

  9. INITIATION: Rate of Self-reported Hypoglycemic Episodes

    Time frame: Endpoint (Initiation: Week 24), Overall (incidence of hypoglycemic episodes after baseline [Week 0])

    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.

  10. INITIATION: Insulin Dose

    Time frame: Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, Endpoint (LOCF)

  11. INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Age

    Time frame: Endpoint (Initiation: Week 24)

    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%).

  12. INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Origin

    Time frame: Endpoint (Initiation: Week 24)

    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%).

  13. INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

    Time frame: Endpoint (Initiation: Week 24)

    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.

  14. INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - HbA1c

    Time frame: Endpoint (Initiation: Week 24)

    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%).

  15. INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - Baseline HbA1c Percentage Group

    Time frame: Endpoint (Initiation: Week 24)

    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%).

  16. INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal at Week 24 - 1,5 AG

    Time frame: Endpoint (Initiation: Week 24)

    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%).

  17. 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

    Time frame: Endpoint (Initiation: Week 24)

    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%).

  18. INITIATION: Participant Demographics of Participants Who Did Versus Did Not Achieve HbA1c Goal - Oral Diabetes Medication at Baseline

    Time frame: Endpoint (Initiation: Week 24)

    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%).

  19. 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)

  20. MAINTENANCE: 7-point SMPG Profiles and Postprandial Excursions

    Time frame: Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years)

    Abbreviations: AM = morning; BG = blood glucose; PM = evening; PP = postprandial. A postprandial excursion is defined as: 2 hour postmeal plasma glucose-premeal plasma glucose.

  21. MAINTENANCE: Rate of Increase in HbA1c

    Time frame: Endpoint (LOCF) (Maintenance: up to 2.5 years)

    Rate of increase: HbA1c change/time period (month).

  22. 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)

  23. 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)

  24. 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)

  25. MAINTENANCE: Insulin Dose

    Time frame: Weeks 24, 36, 48, 60, 72, 84, 96, 108, 120, Endpoint (LOCF) (Maintenance) (up to 2.5 years)

  26. MAINTENANCE: Percentage of Participants With Self-reported Hypoglycemic Episodes

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years), Overall (incidence of hypoglycemic episodes after baseline (Week 0)

    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.

  27. MAINTENANCE: Rate of Self-reported Hypoglycemic Episodes

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years), Overall (incidence of hypoglycemic episodes after baseline [Week 0])

    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.

  28. MAINTENANCE: Change From Baseline in 1,5-Anhydroglucitol

    Time frame: Baseline (Maintenance: Week 24), Endpoint (LOCF) (up to 2.5 years)

  29. MAINTENANCE: Change From Baseline to Endpoint in HbA1c

    Time frame: Baseline (Week 0), Week 24, Endpoint (LOCF) (Maintenance) (up to 2.5 years)

  30. MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  31. MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  32. MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes Group

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  33. MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Duration of Diabetes Group

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  34. MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  35. MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  36. MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c Group

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  37. MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Baseline HbA1c Group

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  38. MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - Oral Diabetes Medicine at Baseline

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  39. MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - Oral Diabetes Medicine at Baseline

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  40. MAINTENANCE: Participant Demographics of Insulin Glargine Participants Who Did Versus Did Not Maintain HbA1c Goal - 1,5 AG

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  41. MAINTENANCE: Participant Demographics of Lispro LM Participants Who Did Versus Did Not Maintain HbA1c Goal - 1,5 AG

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  42. 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

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  43. 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

    Time frame: Endpoint (LOCF) (Maintenance) (up to 2.5 years)

    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%.

  44. ADDENDUM: Change in HbA1c From Point of Second Randomization (Addendum Baseline) to Endpoint

    Time frame: Baseline (Addendum: Week 24), Endpoint (24 weeks [Week 48])

  45. ADDENDUM: Percentage of Participants With HbA1c < or = 7.0%, HbA1c < 7.0%, and < or = 6.5%

    Time frame: Endpoint (Addendum: 24 weeks [Week 48])

  46. ADDENDUM: 7-point SMPG Profiles

    Time frame: Endpoint (Addendum: 24 weeks [Week 48])

    Abbreviations: AM = morning; BG = blood glucose; PM = evening; PP = postprandial. A postprandial excursion is defined as: 2 hour postmeal plasma glucose-premeal plasma glucose.

  47. 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)

  48. ADDENDUM: Body Weight

    Time frame: Baseline (Addendum Week 24), Weeks 6 (30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)

  49. 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)

  50. ADDENDUM: Percentage of Participants With Self-reported Hypoglycemic Episodes

    Time frame: Weeks 6 (Addendum: 30 weeks), 12 (36 weeks), 24 (48 weeks), Endpoint (LOCF)

    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.

  51. ADDENDUM: Rate of Self-reported Hypoglycemic Episodes

    Time frame: Endpoint (Addendum 24 weeks), Overall (mean yearly rate of hypoglycemia during addendum phase

    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.

  52. ADDENDUM: Change From Baseline in 1,5-Anhydroglucitol to Week 24

    Time frame: Baseline (addendum: 24 weeks), Endpoint (24 weeks: Week 48)

  53. ADDENDUM: HbA1c at Specified Visits and Endpoint

    Time frame: Baseline (Addendum: 24 weeks), Weeks 12, 24, Endpoint (24 weeks: Week 48)

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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

Acronym: IOOV

Important dates

Study start
2005
Primary completion
2009
Study completion
2009
First posted
Jan 19, 2006
Registry last updated
Feb 21, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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