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.

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.