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
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: 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
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Repaglinide
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014