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

Phase 4

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Metformin; Drug: Insulin BIAsp30 (Novolog 70/30); Drug: Repaglinide; Drug: Placebo-Repaglinide; Drug: Placebo-Metformin

• Registration Number: NCT00118963
• Lead Sponsor: Steno Diabetes Center Copenhagen

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 Timeline

• Study Start: 2003-01
• Study First Submitted: 2005-07-01
• Study First Submitted QC: 2005-07-01
• Study First Posted: 2005-07-12
• Primary Completion: 2006-02
• Study Completion: 2006-02
• Status Verified: 2008-12
• Last Update Submitted: 2008-12-05
• Last Update Posted: 2008-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 102

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3	Metformin	BIAsp30 plus Metformin plus Placebo-Repaglinide. Double-Masked and randomized. Duration: 12 months.
3	Insulin BIAsp30 (Novolog 70/30)	BIAsp30 plus Metformin plus Placebo-Repaglinide. Double-Masked and randomized. Duration: 12 months.
3	Placebo-Repaglinide	BIAsp30 plus Metformin plus Placebo-Repaglinide. Double-Masked and randomized. Duration: 12 months.
2	Insulin BIAsp30 (Novolog 70/30)	BIAsp30 plus Repaglinide plus Placebo-Metformin. Double-masked and randomized. Duration: 12 months.
2	Placebo-Metformin	BIAsp30 plus Repaglinide plus Placebo-Metformin. Double-masked and randomized. Duration: 12 months.
2	Repaglinide	BIAsp30 plus Repaglinide plus Placebo-Metformin. Double-masked and randomized. Duration: 12 months.
1	Metformin	Run-in period of four months duration with Repaglinide 6 mg daily plus Metformin 2000 mg daily. No masking of interventions.
1	Repaglinide	Run-in period of four months duration with Repaglinide 6 mg daily plus Metformin 2000 mg daily. No masking of interventions.

Primary Outcome Measures

Name	Time	Method
Glycemic control (HbA1c).

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Steno Diabetes Center; 🇩🇰 Gentofte, Denmark