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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
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Metformin
Drug: Insulin BIAsp30 (Novolog 70/30)
Drug: Repaglinide
Drug: Placebo-Metformin
Drug: Placebo-Repaglinide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Steno Diabetes Center:

Primary Outcome Measures:
  • Glycemic control (HbA1c).

Secondary Outcome Measures:
  • 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

Enrollment: 102
Study Start Date: January 2003
Study Completion Date: February 2006
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 3
BIAsp30 plus Metformin plus Placebo-Repaglinide. Double-Masked and randomized. Duration: 12 months.
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: Placebo-Repaglinide
Tablet corresponding to 1 mg; two tablets three times daily.
Active Comparator: 2
BIAsp30 plus Repaglinide plus Placebo-Metformin. Double-masked and randomized. Duration: 12 months.
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.
1
Run-in period of four months duration with Repaglinide 6 mg daily plus Metformin 2000 mg daily. No masking of interventions.
Drug: Metformin
Tablets of 500 mg; 1000 mg two times daily.
Drug: Repaglinide
Tablets of 1 mg; Dosage: 2 mg three times daily.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00118963

Locations
Denmark
Steno Diabetes Center
Gentofte, Denmark, 2820
Sponsors and Collaborators
Steno Diabetes Center
Investigators
Study Chair: Allan A Vaag, M.D. Chief Physician Steno Diabetes Center
  More Information

No publications provided by Steno Diabetes Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00118963     History of Changes
Other Study ID Numbers: Reform
Study First Received: July 1, 2005
Last Updated: December 5, 2008
Health Authority: Denmark: Danish Medicines Agency

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

ClinicalTrials.gov processed this record on November 24, 2014