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

Phase 4
Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Other: Diet-only.
Drug: Placebo-Metformin.
Drug: Placebo-Repaglinide.
Registration Number
NCT00118950
Lead Sponsor
Steno Diabetes Center Copenhagen
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
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

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
3Diet-only.Wash-out period: Treatment: Diet-only: Duration: One month.
2Placebo-Metformin.Repaglinide plus Placebo-Metformin. Double-masked, randomized. Duration: Four months.
1Diet-only.Run-in period: Treatment: Diet-only. Duration: One month.
4MetforminMetformin plus placebo-Repgalinide. Double-masked, randomized. Duration: Four months.
2RepaglinideRepaglinide plus Placebo-Metformin. Double-masked, randomized. Duration: Four months.
4Placebo-Repaglinide.Metformin plus placebo-Repgalinide. Double-masked, randomized. Duration: Four months.
Primary Outcome Measures
NameTimeMethod
HaemoglobinA1c
Secondary Outcome Measures
NameTimeMethod
Waist- and hip-circumference
Home-monitored 7-point plasma-glucose profiles
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.).
Platelet aggregation, markers of platelet activity and fibrinolytic markers fasting as well as before and after physical activity.
Body-weight
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.
DNA for genotyping.
Adverse events and safety variables (e.g. hypoglycaemia, haemoglobin, white blood cell count, cobalamine and folate).

Trial Locations

Locations (1)

Steno Diabetes Center

🇩🇰

Gentofte, Denmark

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