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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00118950
• Other study ID #: ReMet
• Status: Completed
• Phase: Phase 4
• First received: July 1, 2005
• Last updated: December 5, 2008
• Start date: March 2001
• Est. completion date: March 2003

Study information

• Verified date: December 2008
• Source: Steno Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: March 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Metformin
Tablet Metformin 500 mg; Dosage: 1000 mg two times daily. Duration: Four months.
• Repaglinide
Tablet Repaglinide 1 mg; Dosage: 2 mg three times daily. Duration: Four months.
• Placebo-Metformin.
Tablet Placebo (corresponding to 500 mg Metformin). Dosage: 2 tablets two times daily. Duration: Four months.
• Placebo-Repaglinide.
Tablet Placebo (corresponding to 1 mg Repaglinide). Dosage: 2 tablets three times daily. Duration: Four months.

Other:
• Diet-only.
Diet-only treatment. Duration: One month.

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center	Gentofte

Sponsors (1)

Lead Sponsor	Collaborator
Steno Diabetes Center

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HaemoglobinA1c
Secondary	Home-monitored 7-point plasma-glucose profiles
Secondary	Body-weight
Secondary	Waist- and hip-circumference
Secondary	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.).
Secondary	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).
Secondary	Albuminuria and 24-hour blood-pressure measurements.
Secondary	Platelet aggregation, markers of platelet activity and fibrinolytic markers fasting as well as before and after physical activity.
Secondary	DNA for genotyping.
Secondary	Adverse events and safety variables (e.g. hypoglycaemia, haemoglobin, white blood cell count, cobalamine and folate).