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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00118963
• Other study ID #: Reform
• Status: Completed
• Phase: Phase 4
• First received: July 1, 2005
• Last updated: December 5, 2008
• Start date: January 2003
• Est. completion date: February 2006

Study information

• Verified date: December 2008
• Source: Steno Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

After four months run-in with repaglinide plus metformin combination-therapy, patients with HemoglobinA1c ≥6.5% will be randomized (baseline=0 month) to repaglinide 2 mg thrice-daily or metformin 1g twice-daily, both in combination with BIAsp30 (30% insulin-aspart; 70% protaminated insulin-aspart) (6U once-daily, pre-dinner) for 12 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: February 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2

Intervention

Drug:
• Metformin
Tablets of 500 mg; 1000 mg two times daily.
• Insulin BIAsp30 (Novolog 70/30)
Subcutaneous injection. Starting dose 6 units. Titration according to glycaemic targets during the entire intervention period.
• Repaglinide
Tablets of 1 mg; Dosage: 2 mg three times daily.
• Placebo-Metformin
Tablets corresponding to 500 mg; two tablets two times daily.
• Placebo-Repaglinide
Tablet corresponding to 1 mg; two tablets three times daily.

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center	Gentofte

Sponsors (1)

Lead Sponsor	Collaborator
Steno Diabetes Center

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic control (HbA1c).
Secondary	Hypoglycaemic events
Secondary	Home monitored plasma-glucose profiles
Secondary	Insulin-dose
Secondary	Non-glycemic cardiovascular risk factors: 24h blood-pressure measurement
Secondary	24h urinary albumin excretion-rate.
Secondary	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
Secondary	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