Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet

This study has been completed.
Sponsor:
Information provided by:
Steno Diabetes Center
ClinicalTrials.gov Identifier:
NCT00118950
First received: July 1, 2005
Last updated: December 5, 2008
Last verified: December 2008
  Purpose

Background: Metformin is the first drug of choice in obese patients with type-2 diabetes (T2DM) due to its antiglycaemic as well as its cardiovascular protective potentials. In non-obese T2DM patients insulin-secretagogues are empirically used as first choice. The aim of this study was to evaluate the effect of metformin versus an insulin-secretagogue, repaglinide on glycaemic regulation and non-glycaemic cardiovascular risk markers in non-obese patients with T2DM.

Methods: Single-center, randomised, double-masked, double-dummy, cross-over-study of 96 non-obese (BMI ≤ 27 kg/m2) Caucasian T2DM-patients. After a one month run-in on diet-only treatment, patients were randomised to either repaglinide 2mg three times a day (t.i.d). followed by metformin 1g twice a day (b.i.d.) or vice versa each for a period of four months with a one month wash-out between interventions.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Metformin
Drug: Repaglinide
Drug: Placebo-Metformin.
Drug: Placebo-Repaglinide.
Other: Diet-only.
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Metformin Versus Repaglinide Treatment on Glycemic Control and Non-Glycaemic Cardiovascular Risk Factors in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet

Resource links provided by NLM:


Further study details as provided by Steno Diabetes Center:

Primary Outcome Measures:
  • HaemoglobinA1c

Secondary Outcome Measures:
  • Home-monitored 7-point plasma-glucose profiles
  • Body-weight
  • Waist- and hip-circumference
  • Fasting and postprandial (after a standard test-meal) measures of plasma-glucose, insulin, c-peptide, free fatty acids, lipoproteins, triglycerides and other markers related to lipid-metabolism (e.g. apo-lipoproteins, lipoprotein particle size etc.).
  • Biomarkers related to inflammation, endothelial dysfunction and fibrinolysis (e.g. hs-CRP, TNF-alpha, IL-6, ICAM, VCAM, E-selectin, vWF, PAI-1 and t-PA, adiponectin, ADMA, AGE-peptides).
  • Albuminuria and 24-hour blood-pressure measurements.
  • Platelet aggregation, markers of platelet activity and fibrinolytic markers fasting as well as before and after physical activity.
  • DNA for genotyping.
  • Adverse events and safety variables (e.g. hypoglycaemia, haemoglobin, white blood cell count, cobalamine and folate).

Estimated Enrollment: 100
Study Start Date: March 2001
Estimated Study Completion Date: March 2003
Arms Assigned Interventions
Active Comparator: 4
Metformin plus placebo-Repgalinide. Double-masked, randomized. Duration: Four months.
Drug: Metformin
Tablet Metformin 500 mg; Dosage: 1000 mg two times daily. Duration: Four months.
Drug: Placebo-Repaglinide.
Tablet Placebo (corresponding to 1 mg Repaglinide). Dosage: 2 tablets three times daily. Duration: Four months.
Active Comparator: 2
Repaglinide plus Placebo-Metformin. Double-masked, randomized. Duration: Four months.
Drug: Repaglinide
Tablet Repaglinide 1 mg; Dosage: 2 mg three times daily. Duration: Four months.
Drug: Placebo-Metformin.
Tablet Placebo (corresponding to 500 mg Metformin). Dosage: 2 tablets two times daily. Duration: Four months.
1
Run-in period: Treatment: Diet-only. Duration: One month.
Other: Diet-only.
Diet-only treatment. Duration: One month.
3
Wash-out period: Treatment: Diet-only: Duration: One month.
Other: Diet-only.
Diet-only treatment. Duration: One month.

  Eligibility

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

Inclusion Criteria:

Type-2 diabetes, defined as:

  • Age at onset of diabetes ≥ 40 years
  • Fasting serum C-peptide ≥ 300 pmol/l or a non-fasting or glucagon-stimulated serum C-peptide ≥ 600 pmol/l
  • No history of ketonuria or ketoacidosis.
  • BMI ≤ 27 kg/m2.
  • Fasting plasma-glucose ≥ 6.5 mmol/l after at least one month of diet-only treatment.
  • HbA1c ≤ 9.5% at ongoing oral anti-hyperglycaemic agents. HbA1c ≥ 6.5% after minimum one month of diet-only treatment.
  • Weight-loss of no more than 5.0 kg during the last 6 months prior to enrolment.

Exclusion Criteria:

  • Type-1 diabetes
  • Insulin-treated type-2 diabetes
  • Secondary diabetes, heart-failure
  • Serum-creatinine above the upper limit
  • Serum-ASAT elevated more than 3 fold above the upper limit
  • Factor II-VII-X decreased below 0.7
  • Ongoing coexisting illnesses with a life-shortening prognosis
  • Mental retardation or reduced intellectual behaviour
  • Pregnancy
  • History of drug-abuse or HbA1c>10.5% at two separate visits with at least one month interval during treatment-periods.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00118950

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
Principal Investigator: Soeren S Lund, M. D. Steno Diabetes Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00118950     History of Changes
Other Study ID Numbers: ReMet
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
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Repaglinide
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014