Clinical trial NCT00118963: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
First posted: 2005-07-12
Enrollment: 102
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Glycemic control (HbA1c).
Secondary outcomes:
measure: Hypoglycaemic events
measure: Home monitored plasma-glucose profiles
measure: Insulin-dose
measure: Non-glycemic cardiovascular risk factors: 24h blood-pressure measurement
measure: 24h urinary albumin excretion-rate.
measure: 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
measure: 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
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Allan A Vaag, M.D. Chief Physician
role: STUDY_CHAIR
References:
citation: Lund SS, Tarnow L, Frandsen M, Nielsen BB, Hansen BV, Pedersen O, Parving HH, Vaag AA. Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial. BMJ. 2009 Nov 9;339:b4324. doi: 10.1136/bmj.b4324.