Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00191464
First received: September 12, 2005
Last updated: October 12, 2010
Last verified: October 2010
  Purpose

The primary objective of this study is to show that a prandial insulin regimen, consisting of premeal insulin lispro "mid mixture" (or a combined regimen of insulin lispro "mid mixture" and insulin lispro "low mixture") plus metformin will result in significantly better overall glycemic control (lower HbA1c) at endpoint than once-daily insulin glargine plus metformin. Insulin lispro "mid mixture" consists of 50% insulin lispro and 50% NPL. Insulin lispro "low mixture" consists of 25% insulin lispro and 75% NPL.

In a substudy of approximately 60 patients, additional data will be collected on markers associated with risk of atherosclerosis or cardiovascular disease in the context of a controlled, outpatient, high-fat test meal.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: premeal insulin lispro mixtures
Drug: insulin glargine
Drug: metformin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes: A Comparison of Premeal Insulin Lispro Mixtures to Once-Daily Insulin Glargine

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • HbA1C

Secondary Outcome Measures:
  • General inflammation (hsCRP)
  • High-density lipoprotein cholesterol
  • Total cholesterol
  • Triglycerides
  • Estimates of low-density lipoprotein cholesterol
  • Nuclear magnetic resonance [NMR] analysis of lipids
  • Oxidized LDL
  • Lipoproteins and apoproteins
  • Fibrinogen
  • Blood glucose levels (based on self-monitoring)
  • Insulin dose
  • Weight
  • Frequency and incidence of hypoglycemia
  • Safety
  • General well-being
  • Pilot two questionnaires for microvascular complications
  • Coagulopathy factors [substudy]
  • Surrogate measure of vascular reactivity [substudy]
  • Inflammatory markers [substudy]
  • Production of advanced glycation end-products [substudy]
  • Generation of oxidative species [substudy]
  • Lipids in various fractions [substudy]
  • Retinyl ester measurements in various fractions [substudy]
  • Composition of triglyceride-rich lipoproteins [substudy]
  • Compartmental modeling of postprandial lipemia [substudy]
  • Apolipoproteins [substudy]

Estimated Enrollment: 320
Study Start Date: December 2003
Estimated Study Completion Date: September 2005
  Eligibility

Ages Eligible for Study:   35 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have type 2 diabetes (World Health Organization [WHO] classification
  • Have used one or more of the following oral anti-hyperglycemic medications-metformin or second-generation sulfonylurea (for example, glibenclamide, glyburide, glipizide, gliclazide, glimepiride) alone or in combination with one or two insulin injections per day for at least 3 months immediately prior to entering the study. Patients using more than 2 insulin injections per day or subcutaneous insulin infusion prior to the study will not be eligible to participate.
  • Have a hemoglobin A1c between 6.5% and 11%, inclusive, according to the central laboratory at Visit 1.
  • Have clinically acceptable LDL-C, in the investigator's opinion, at Visit 1.
  • As determined by the investigator, are capable and willing to learn how to use the insulin injection pens; comply with their prescribed diet, exercise, and medication regimen; perform self-monitoring of blood glucose; and use the patient diary as required for this protocol.

Exclusion Criteria:

  • Have hypersensitivity to metformin or a known allergy to metformin hydrochloride, insulin lispro MM, insulin lispro LM, or insulin glargine, or excipients contained in these products.
  • Have known metabolic or lactic acidosis.
  • Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than or equal to 135 micromol/L (1.5 mg/dL) for males and greater than or equal to 110 micromol/L (1.2 mg/dL) for females.
  • Have cardiac disease with functional status that is Class III or IV
  • Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine transaminase (ALT) greater than three times the upper limit of the reference range as defined by the central laboratory.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00191464

Locations
United States, New Hampshire
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Lebanon, New Hampshire, United States, 03756
Australia, New South Wales
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
St Leonards, New South Wales, Australia, 2065
Greece
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Thessaloniki, Greece, 56429
India
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Mumbai, Maharstra, India, 400 007
Netherlands
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Den Helder, Netherlands, 1783 GZ
Poland
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Olesnica, Poland, 56-400
Puerto Rico
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Ponce, Puerto Rico, 00731
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00191464     History of Changes
Other Study ID Numbers: 6146, F3Z-MC-IOOI
Study First Received: September 12, 2005
Last Updated: October 12, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin LISPRO
Glargine
Insulin
Metformin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014