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Lispro Mid Mixture (MM) Intensive Mixture Therapy With Progressive Dose-Titration of Lispro Low Mixture (LM) or Biphasic Insulin Aspart 30/70 (S019)

Phase 4
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Drug: insulin lispro LM
Drug: Insulin Biphasic Aspart 30/70
Drug: insulin lispro MM
Registration Number
NCT00393705
Lead Sponsor
Eli Lilly and Company
Brief Summary

Investigation into patients with type 2 diabetes mellitus not achieving adequate glycemic control while treated with combination of premixed insulin analogue formulations twice daily and metformin will be randomly assigned to follow one of two insulin treatment strategies used in combination with metformin administration. The aim of the trial is to try to achieve optimal metabolic control and explore full therapeutic potential of the strategies, patients in both arms will follow progressive insulin dose titration algorithms for 16 weeks.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
302
Inclusion Criteria
  • Have type 2 diabetes (World Health Organization [WHO] classification).
  • Are at least 30 years of age and less than 75 years of age.
  • Have been receiving hypoglycemic treatment with premixed insulin analogue (either with insulin lispro LM or biphasic insulin aspart 30/70) administered twice daily in combination with at least 1500 milligrams (mg) of metformin per day for at least 60 days immediately prior to the study.
  • Have a hemoglobin A1c 1.2 to 1.8 times the upper limit of the normal reference range at the local laboratory at Visit 1 or
  • Have at least 6 of 9 of the postprandial blood glucose values recorded in the period between Visit 1 and Visit 2 exceeding 180 milligrams per 100 milliliters (mg/dl) (10.0 millimole per liter [mmol/l]).
  • Have given written informed consent to participate in this study in accordance with local regulations.
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Exclusion Criteria
  • Are taking any other oral anti-diabetic medication (OAM) not mentioned in inclusion criterion.
  • Have a body mass index greater than 40 kilograms per meter squared (kg/m2).
  • Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study.
  • Have congestive heart failure.
  • Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
insulin lispro LM + insulin lispro MMinsulin lispro LMThree times per day subcutaneous injection of insulin lispro mid mixture (MM) with the possibility to change the evening injection of MM to insulin lispro low mixture (LM) if fasting blood glucose target is not achieved.
insulin lispro LM + insulin lispro MMinsulin lispro MMThree times per day subcutaneous injection of insulin lispro mid mixture (MM) with the possibility to change the evening injection of MM to insulin lispro low mixture (LM) if fasting blood glucose target is not achieved.
Insulin Biphasic Aspart 30/70 or Insulin Lispro LMInsulin Biphasic Aspart 30/70Twice daily subcutaneous injection of either insulin biphasic aspart 30/70 or insulin lispro low mixture (LM) (continuation of analogue formulation used before study enrollment).
Insulin Biphasic Aspart 30/70 or Insulin Lispro LMinsulin lispro LMTwice daily subcutaneous injection of either insulin biphasic aspart 30/70 or insulin lispro low mixture (LM) (continuation of analogue formulation used before study enrollment).
Primary Outcome Measures
NameTimeMethod
Hemoglobin A1c (HbA1c) at 16 Week Endpoint16 weeks
Secondary Outcome Measures
NameTimeMethod
Percentage of Patients Achieving Hemoglobin A1c (HbA1c) <7% and HbA1c ≤6.5% at 16 Week Endpoint16 weeks
Change From Baseline in Hemoglobin A1c (HbA1c) at 16 Week EndpointBaseline, 16 Weeks
2-hour Postprandial Plasma Glucose Concentrations After the Midday Meal From Self-monitored 7-point Plasma Glucose at 16 Week Endpoint16 weeks

Participants self-monitored their blood glucose concentrations at 7 time points: three premeal and three 2-hour postprandial meal measurements for the morning (breakfast), midday (lunch), and evening (dinner) meals, as well as a 3:00 AM measurement. Results presented here are for the blood glucose concentrations 2-hours after the midday meal at Week 16.

Mean 2-hour Postprandial Blood Glucose Excursions After Midday Meal at 16 Week Endpoint16 weeks

Participants self-monitored their blood glucose concentrations at 7 time points: three premeal and three 2-hour postprandial meal measurements for the morning (breakfast), midday (lunch), and evening (dinner) meals, as well as a 3:00 AM measurement. Results presented here are for the difference (excursion) between midday premeal and 2-hour postprandial midday meal blood glucose concentrations at Week 16.

Mean Daily Blood Glucose Values at 16 Week Endpoint16 weeks
Number of Patients With Self-reported Hypoglycemic EpisodesBaseline through 16 weeks

Hypoglycemia: any time a patient feels, or another person observes, that patient is experiencing a sign/symptom that he or she would associate with hypoglycemia or a plasma-equivalent glucose measurement ≤70 mg/dL. Nocturnal hypoglycemia: hypoglycemia occurring after bedtime and prior to morning meal and morning dose of insulin or metformin. Severe hypoglycemia: hypoglycemia where patient requires assistance from another person and which is associated with either a blood glucose level less than 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.

30-Day Adjusted Rate of Hypoglycemic EventsBaseline through 16 weeks

Hypoglycemia: any time a patient feels, or another person observes, that patient is experiencing a sign/symptom that he or she would associate with hypoglycemia or a plasma-equivalent glucose measurement ≤70 mg/dL. Nocturnal hypoglycemia: hypoglycemia occurring after bedtime and prior to morning meal and morning dose of insulin or metformin. Severe hypoglycemia: hypoglycemia where patient requires assistance from another person and which is associated with either a blood glucose level less than 50 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration.

Change From Baseline in Weight at 16 Week EndpointBaseline, 16 weeks
Total Daily Insulin Dose at 4 Weeks and 12 Weeks4 weeks and 12 weeks

Trial Locations

Locations (1)

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.

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Konya, Turkey

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