Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes

This study has been completed.
Sponsor:
Information provided by:
Steno Diabetes Center
ClinicalTrials.gov Identifier:
NCT00118963
First received: July 1, 2005
Last updated: December 5, 2008
Last verified: December 2008

July 1, 2005
December 5, 2008
January 2003
February 2006   (final data collection date for primary outcome measure)
Glycemic control (HbA1c).
Same as current
Complete list of historical versions of study NCT00118963 on ClinicalTrials.gov Archive Site
  • Hypoglycaemic events
  • Home monitored plasma-glucose profiles
  • Insulin-dose
  • Non-glycemic cardiovascular risk factors: 24h blood-pressure measurement
  • 24h urinary albumin excretion-rate.
  • Fasting and postprandial 5-point-profiles of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, free fatty acids, p-glucose, c-peptide and insulin after a standard test-meal
  • Markers of endothelial dysfunction, inflammation and fibrinolysis including Small-dense-LDL, Lp(a) and Apo B100, von Willebrand-factor, ICAM, VCAM, selectin, endothelin, Amadori-protein, CRP, fibrinogen, IL-6, TNF-alfa, ADMA, PAI- and t-PA-activity
  • Hypoglycaemic events
  • Home monitored plasma-glucose profiles
  • Insulin-dose
  • Non-glycemic cardiovascular risk factors:
  • 24h blood-pressure measurement
  • 24h urinary albumin excretion-rate.
  • Fasting and postprandial 5-point-profiles of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, free fatty acids, p-glucose, c-peptide and insulin after a standard test-meal
  • Markers of endothelial dysfunction, inflammation and fibrinolysis including Small-dense-LDL, Lp(a) and Apo B100, von Willebrand-factor, ICAM, VCAM, selectin, endothelin, Amadori-protein, CRP, fibrinogen, IL-6, TNF-alfa, ADMA, PAI- and t-PA-activity
Not Provided
Not Provided
 
Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
Effect of Repaglinide Versus Metformin Treatment in Combination With Insulin Biasp30 (Novologmix 70/30) Predinner on Glycemic and Non-Glycemic Cardiovascular Risk-Factors in Non-Obese Patients With Type-2-Diabetes With Unsatisfactory Glycaemic Control With Oral Hypoglycaemic Agents

Aim:

The United Kingdom Prospective Diabetes Study (UKPDS) showed a reduction in cardiovascular events in obese patients with type-2-diabetes treated with metformin compared with other hypoglycaemic treatments with no difference in glycemic control between treatments. Non-obese patients with type-2-diabetes are usually treated with insulin-secretagogues or insulin when diet fails. Since non-obese patients with type-2-diabetes also carry a high risk of cardiovascular events, the use of metformin for this sub-group of patients might be more beneficial. Moreover, when insulin-treatment is initiated ongoing oral hypoglycaemic agents (OHA) are often continued, but in non-obese patients with type-2 diabetes little evidence exist for choosing the optimal class of OHA to be combined with insulin. The aim of the project is therefore to investigate the effect of metformin vs. an insulin-secretagogue (repaglinide) in combination with insulin on glycemic control and non-glycemic cardiovascular risk-factors in non-obese patients with type-2-diabetes, uncontrolled on diet alone.

Methodology:

Single-center, double-blind, double-dummy, randomized, parallel study involving 100 non-obese (BMI 27 kg/m2 or lower) patients with type-2-diabetes investigating the effect of treatment with metformin vs. repaglinide each in combination with biphasic insulin (Insulin-aspart 30/70, BIAsp30) for a period of 12 months.

After four months run-in with repaglinide plus metformin combination-therapy, patients with HemoglobinA1c ≥6.5% will be randomized (baseline=0 month) to repaglinide 2 mg thrice-daily or metformin 1g twice-daily, both in combination with BIAsp30 (30% insulin-aspart; 70% protaminated insulin-aspart) (6U once-daily, pre-dinner) for 12 months.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Diabetes Mellitus, Type 2
  • Drug: Metformin
    Tablets of 500 mg; 1000 mg two times daily.
  • Drug: Insulin BIAsp30 (Novolog 70/30)
    Subcutaneous injection. Starting dose 6 units. Titration according to glycaemic targets during the entire intervention period.
  • Drug: Repaglinide
    Tablets of 1 mg; Dosage: 2 mg three times daily.
  • Drug: Placebo-Metformin
    Tablets corresponding to 500 mg; two tablets two times daily.
  • Drug: Placebo-Repaglinide
    Tablet corresponding to 1 mg; two tablets three times daily.
  • Active Comparator: 3
    BIAsp30 plus Metformin plus Placebo-Repaglinide. Double-Masked and randomized. Duration: 12 months.
    Interventions:
    • Drug: Metformin
    • Drug: Insulin BIAsp30 (Novolog 70/30)
    • Drug: Placebo-Repaglinide
  • Active Comparator: 2
    BIAsp30 plus Repaglinide plus Placebo-Metformin. Double-masked and randomized. Duration: 12 months.
    Interventions:
    • Drug: Insulin BIAsp30 (Novolog 70/30)
    • Drug: Repaglinide
    • Drug: Placebo-Metformin
  • 1
    Run-in period of four months duration with Repaglinide 6 mg daily plus Metformin 2000 mg daily. No masking of interventions.
    Interventions:
    • Drug: Metformin
    • Drug: Repaglinide
Lund SS, Tarnow L, Frandsen M, Nielsen BB, Hansen BV, Pedersen O, Parving HH, Vaag AA. Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial. BMJ. 2009 Nov 9;339:b4324.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
102
February 2006
February 2006   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Non-obese patients (BMI < 27 kg/m2)
  • Type 2 diabetes
  • Age 40 years or older
  • HbA1c = 6.5% or higher at baseline.

Exclusion Criteria:

  • No known contraindications for either of the study-drugs (known allergy to the study-drugs; heart-, liver- or kidney-failure)
  • Pregnancy
  • Other serious physical or mental illnesses with a life-shortening prognosis.
  • Drug or alcohol abuse.
  • Weight-loss of more than 5 kg during the last 6 month prior to enrollment.
Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Denmark
 
NCT00118963
Reform
Not Provided
Not Provided
Steno Diabetes Center
Not Provided
Study Chair: Allan A Vaag, M.D. Chief Physician Steno Diabetes Center
Steno Diabetes Center
December 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP