Clinical trial NCT00118950: Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
First posted: 2005-07-12
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: HaemoglobinA1c
Secondary outcomes:
measure: Home-monitored 7-point plasma-glucose profiles
measure: Body-weight
measure: Waist- and hip-circumference
measure: 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.).
measure: 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).
measure: Albuminuria and 24-hour blood-pressure measurements.
measure: Platelet aggregation, markers of platelet activity and fibrinolytic markers fasting as well as before and after physical activity.
measure: DNA for genotyping.
measure: Adverse events and safety variables (e.g. hypoglycaemia, haemoglobin, white blood cell count, cobalamine and folate).
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Allan A Vaag, M. D., Chief Physician
role: STUDY_CHAIR
affiliation: Steno Diabetes Center Copenhagen
name: Soeren S Lund, M. D.
role: PRINCIPAL_INVESTIGATOR
References: