Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes

Condition(s) targeted: Diabetes Mellitus, Type 2

Intervention: Metformin or placebo (Drug); Insulin BIAsp30 (Novolog 70/30) (Drug); Repaglinide or placebo (Drug)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: Steno Diabetes Center

Official(s) and/or principal investigator(s):
Allan A Vaag, M.D. Chief Physician, Study Chair, Affiliation: Steno Diabetes Center

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.

Official title: Effect of Repaglinide Versus Metformin Treatment in Combination With Insulin Biasp30 (Novologmix 70/30) Predinner on Glycemic and Non-Glycemic Cardiovascular Risk-Factors in Non-Obese Patients With Type-2-Diabetes With Unsatisfactory Glycaemic Control With Oral Hypoglycaemic Agents

Study design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Glycemic control (HbA1c).

Secondary outcome:

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

Minimum age: 40 Years. Maximum age: N/A. Gender(s): 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.

Steno Diabetes Center, Gentofte 2820, Denmark

Starting date: January 2003
Last updated: July 20, 2005