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”

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.

Study Type: Interventional

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

Intervention(s) in this Clinical Trial

• Drug: Metformin
  • Tablet Metformin 500 mg; Dosage: 1000 mg two times daily. 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.
• Drug: 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.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 4
  • Metformin plus placebo-Repgalinide. Double-masked, randomized. Duration: Four months.
• Active Comparator: 2
  • Repaglinide plus Placebo-Metformin. Double-masked, randomized. Duration: Four months.
• Other: 1
  • Run-in period: Treatment: Diet-only. Duration: One month.
• Other: 3
  • Wash-out period: Treatment: Diet-only: Duration: One month.

Primary Measures

• HaemoglobinA1c

Secondary 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).

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Steno Diabetes Center

Overall Clinical Trial Officials and Contacts

Allan A Vaag, M. D., Chief Physician Study Chair Steno Diabetes Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00118950

Study ID Number: ReMet

ClinicalTrials.gov Identifier: NCT00118950

Health Authority: Denmark: Danish Medicines Agency