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

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

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Purpose	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	Diabetes Mellitus, Type 2
Intervention	Drug: Metformin Drug: Insulin BIAsp30 (Novolog 70/30) Drug: Repaglinide Drug: Placebo-Metformin Drug: Placebo-Repaglinide
Phase	Phase 4
Sponsor	Steno Diabetes Center
Responsible Party	Steno Diabetes Center
ClinicalTrials.gov Identifier	NCT00118963
First Received	July 1, 2005
Last Updated	December 5, 2008
Last verified	December 2008

Tracking Information[ + expand ][ + ]

First Received Date	July 1, 2005
Last Updated Date	December 5, 2008
Start Date	January 2003
Estimated Primary Completion Date	February 2006
Current Primary Outcome Measures	Glycemic control (HbA1c).
Current Secondary Outcome Measures	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

Descriptive Information[ + expand ][ + ]

Brief Title	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
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
Brief 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.
Detailed 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.
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	Diabetes Mellitus, Type 2
Intervention	Drug: Metformin Tablets of 500 mg; 1000 mg two times daily. Drug: Insulin BIAsp30 (Novolog 70/30) Subcutaneous injection. Starting dose 6 units. Titration according to glycaemic targets during the entire intervention period. Drug: Repaglinide Tablets of 1 mg; Dosage: 2 mg three times daily. Drug: Placebo-Metformin Tablets corresponding to 500 mg; two tablets two times daily. Drug: Placebo-Repaglinide Tablet corresponding to 1 mg; two tablets three times daily.
Study Arm (s)	Active Comparator: 3 BIAsp30 plus Metformin plus Placebo-Repaglinide. Double-Masked and randomized. Duration: 12 months. Active Comparator: 2 BIAsp30 plus Repaglinide plus Placebo-Metformin. Double-masked and randomized. Duration: 12 months. Other: 1 Run-in period of four months duration with Repaglinide 6 mg daily plus Metformin 2000 mg daily. No masking of interventions.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	102
Estimated Completion Date	February 2006
Estimated Primary Completion Date	February 2006
Eligibility 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.
Gender	Both
Ages	40 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Denmark

Administrative Information[ + expand ][ + ]

NCT Number	NCT00118963
Other Study ID Numbers	Reform
Has Data Monitoring Committee	Not Provided
Information Provided By	Steno Diabetes Center
Study Sponsor	Steno Diabetes Center
Collaborators	Not Provided
Investigators	Study Chair: Allan A Vaag, M.D. Chief Physician Steno Diabetes Center
Verification Date	December 2008

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