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

Sponsored by:	Steno Diabetes Center
Information provided by:	Steno Diabetes Center
ClinicalTrials.gov Identifier:	NCT00118950

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 IV

MedlinePlus related topics: Diabetes

Drug Information available for: Metformin Metformin hydrochloride AG-EE 388 ZW

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Efficacy Study
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

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
4: Active Comparator 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.
2: Active Comparator 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

Study ID Numbers:	ReMet
Study First Received:	July 1, 2005
Last Updated:	December 5, 2008
ClinicalTrials.gov Identifier:	NCT00118950
Health Authority:	Denmark: Danish Medicines Agency

Study placed in the following topic categories:

Metabolic Diseases
Metformin
Diabetes Mellitus, Type 2
Diabetes Mellitus
Endocrine System Diseases

Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders
Repaglinide

Additional relevant MeSH terms:

Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009