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

NCT00118950 | Completed Phase 4

• 1 other identifier: ReMet
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• HaemoglobinA1c

Secondary Outcomes (9)

• 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).

Study Arms (4)

4

ACTIVE COMPARATOR

Metformin plus placebo-Repgalinide. Double-masked, randomized. Duration: Four months.

Drug: Metformin; Drug: Placebo-Repaglinide.

2

ACTIVE COMPARATOR

Repaglinide plus Placebo-Metformin. Double-masked, randomized. Duration: Four months.

Drug: Repaglinide; Drug: Placebo-Metformin.

1

OTHER

Run-in period: Treatment: Diet-only. Duration: One month.

Other: Diet-only.

3

OTHER

Wash-out period: Treatment: Diet-only: Duration: One month.

Other: Diet-only.

Interventions

Metformin DRUG

Tablet Metformin 500 mg; Dosage: 1000 mg two times daily. Duration: Four months.

4

Repaglinide DRUG

Tablet Repaglinide 1 mg; Dosage: 2 mg three times daily. Duration: Four months.

2

Placebo-Metformin. DRUG

Tablet Placebo (corresponding to 500 mg Metformin). Dosage: 2 tablets two times daily. Duration: Four months.

2

Placebo-Repaglinide. DRUG

Tablet Placebo (corresponding to 1 mg Repaglinide). Dosage: 2 tablets three times daily. Duration: Four months.

4

Diet-only. OTHER

Diet-only treatment. Duration: One month.

1; 3

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead

Study Sites (1)

Steno Diabetes Center

Gentofte Municipality, 2820, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; repaglinide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Allan A Vaag, M. D., Chief Physician

  Steno Diabetes Center Copenhagen

  STUDY CHAIR

• Soeren S Lund, M. D.

  Steno Diabetes Center Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 1, 2005
• First Posted: July 12, 2005
• Study Start: March 1, 2001
• Study Completion: March 1, 2003
• Last Updated: December 8, 2008

Record last verified: 2008-12

Locations

DK (1)