Aim: The United Kingdom Prospective Diabetes Study (UKPDS) showed a reduction in cardiovascular events in obese patients with type-2-diabetes treated with metformin compared with other hypoglycaemic treatments with no difference in glycemic control between treatments. Non-obese patients with type-2-diabetes are usually treated with insulin-secretagogues or insulin when diet fails. Since non-obese patients with type-2-diabetes also carry a high risk of cardiovascular events, the use of metformin for this sub-group of patients might be more beneficial. Moreover, when insulin-treatment is initiated ongoing oral hypoglycaemic agents (OHA) are often continued, but in non-obese patients with type-2 diabetes little evidence exist for choosing the optimal class of OHA to be combined with insulin. The aim of the project is therefore to investigate the effect of metformin vs. an insulin-secretagogue (repaglinide) in combination with insulin on glycemic control and non-glycemic cardiovascular risk-factors in non-obese patients with type-2-diabetes, uncontrolled on diet alone.

Methodology: Single-center, double-blind, double-dummy, randomized, parallel study involving 100 non-obese (BMI 27 kg/m2 or lower) patients with type-2-diabetes investigating the effect of treatment with metformin vs. repaglinide each in combination with biphasic insulin (Insulin-aspart 30/70, BIAsp30) for a period of 12 months.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: Metformin or placebo  Drug: Insulin BIAsp30 (Novolog 70/30)  Drug: Repaglinide or placebo	Phase IV

Further Study Details: 

Primary Outcomes: Glycemic control (HbA1c).
Secondary Outcomes: Hypoglycaemic events; Home monitored plasma-glucose profiles; Insulin-dose; Non-glycemic cardiovascular risk factors: 24h blood-pressure measurement; 24h urinary albumin excretion-rate.; Fasting and postprandial 5-point-profiles of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, free fatty acids, p-glucose, c-peptide and insulin after a standard test-meal; Markers of endothelial dysfunction, inflammation and fibrinolysis including Small-dense-LDL, Lp(a) and Apo B100, von Willebrand-factor, ICAM, VCAM, selectin, endothelin, Amadori-protein, CRP, fibrinogen, IL-6, TNF-alfa, ADMA, PAI- and t-PA-activity
Expected Total Enrollment:  100

Ages Eligible for Study:  40 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Non-obese patients (BMI < 27 kg/m2)
• Type 2 diabetes
• Age 40 years or older
• HbA1c = 6.5% or higher at baseline.

Exclusion Criteria:

• No known contraindications for either of the study-drugs (known allergy to the study-drugs; heart-, liver- or kidney-failure)
• Pregnancy
• Other serious physical or mental illnesses with a life-shortening prognosis.
• Drug or alcohol abuse.
• Weight-loss of more than 5 kg during the last 6 month prior to enrollment.

Denmark
      Steno Diabetes Center, Gentofte,  2820,  Denmark

Study chairs or principal investigators

Allan A Vaag, M.D. Chief Physician,  Study Chair,  Steno Diabetes Center   

Study ID Numbers:  Reform
Last Updated:  August 1, 2005
Record first received:  July 11, 2005
ClinicalTrials.gov Identifier:  NCT00118963
Health Authority: Denmark: Danish Medicines Agency
ClinicalTrials.gov processed this record on 2005-08-02