Diabetes Mellitus, Type 2
Conditions
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.
Interventions
DRUGMetformin
Tablet Metformin 500 mg; Dosage: 1000 mg two times daily. Duration: Four months.
DRUGRepaglinide
Tablet Repaglinide 1 mg; Dosage: 2 mg three times daily. Duration: Four months.
DRUGPlacebo-Metformin.
Tablet Placebo (corresponding to 500 mg Metformin). Dosage: 2 tablets two times daily. Duration: Four months.
DRUGPlacebo-Repaglinide.
Tablet Placebo (corresponding to 1 mg Repaglinide). Dosage: 2 tablets three times daily. Duration: Four months.
OTHERDiet-only.
Diet-only treatment. Duration: One month.
Sponsors
Steno Diabetes Center Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HaemoglobinA1c | — |
Secondary
| Measure | Time frame |
|---|---|
| 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). | — |
| Home-monitored 7-point plasma-glucose profiles | — |
| 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). | — |
| Albuminuria and 24-hour blood-pressure measurements. | — |
Countries
Denmark
Outcome results
None listed