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

• ClinicalTrials.gov Identifier: NCT00118950
• Recruitment Status: Completed
• First Posted: July 12, 2005
• Last Update Posted: December 8, 2008
• Sponsor: Steno Diabetes Center Copenhagen
• Information provided by: Steno Diabetes Center Copenhagen

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Drug: Metformin; Drug: Repaglinide; Drug: Placebo-Metformin.; Drug: Placebo-Repaglinide.; Other: Diet-only.	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: March 2001
• Study Completion Date: March 2003

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. HaemoglobinA1c

Secondary Outcome Measures :

1. Home-monitored 7-point plasma-glucose profiles
2. Body-weight
3. Waist- and hip-circumference
4. 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.).
5. 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).
6. Albuminuria and 24-hour blood-pressure measurements.
7. Platelet aggregation, markers of platelet activity and fibrinolytic markers fasting as well as before and after physical activity.
8. DNA for genotyping.
9. Adverse events and safety variables (e.g. hypoglycaemia, haemoglobin, white blood cell count, cobalamine and folate).

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Denmark

Steno Diabetes Center

Gentofte, Denmark, 2820

Sponsors and Collaborators

Steno Diabetes Center Copenhagen

Investigators

• Study Chair: Allan A Vaag, M. D., Chief Physician; Steno Diabetes Center Copenhagen
• Principal Investigator: Soeren S Lund, M. D.; Steno Diabetes Center Copenhagen

More Information

• ClinicalTrials.gov Identifier: NCT00118950
• Other Study ID Numbers: ReMet
• First Posted: July 12, 2005
• Last Update Posted: December 8, 2008
• Last Verified: December 2008

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Metformin; Repaglinide; Hypoglycemic Agents; Physiological Effects of Drugs