Insulin Glargine U300 vs Insulin Degludec U100 in Impact on the Glycaemic and Cardiovascular Factors

Study Overview
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Brief Summary
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To compare the impact of insulin degludec (IDeg-100) and insulin glargine U300 (IGlar-300) on cardiovascular risk parameters - glycaemic variability (GV), oxidative stress, arterial stiffness and lipid parameters - in insulin naive patients with DMT2.

Detailed Description
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We recruited a total of 25 patients (23 completed the study) with T2DM who had uncontrolled disease on two or more oral antidiabetic drugs. After the wash-up period, they were randomized alternately to first receive either IDeg-100 or IGlar-300 along with metformin. Each insulin was applied for 12 weeks. At the beginning and the end of each phase, biochemical and oxidative stress parameters were analysed and augmentation index was measured. On three consecutive days prior to each control point, patients performed a 7-point SMBG profile. Oxidative stress was assessed by measuring thiol groups and hydroperoxides (d-ROM) in serum. For augmentation index measuring, we used SphygmoCor (AtCor Medical, Sydney, Australia) which allow non-invasive measurement of AIx on radial artery using strain gauge transducer placed on the tip of a pencil-type tonometer. This method is based on the principle of applanation tonometry

Official Title
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The Differences Between Insulin Glargine U300 and Insulin Degludec U100 in Impact on the Glycaemic Variability, Oxidative Stress, Arterial Stiffness and the Lipid Profiles in Insulin naïve Patients Suffering From Type Two Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Degludec
* Drug: Glargine U300


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a history of DMT2 for at least 1 year aged between 18 and 65 years (women obligatory postmenopausal) uncontrolled glycaemia on two or more oral antidiabetic drugs no prior use of insulin HbA1c ≥7.5% receiving statins (if not on statins, they were put on it) not on antiaggregant therapy (if on antiaggregants, they were temporarily excluded from therapy) Exclusion criteria: the presence of malignant disease chronic liver disease renal impairment with creatinine clearance < 60 ml/s severe cardiovascular disease or history of cardiovascular incidents (stroke, myocardial infarction, peripheral amputation) rheumatic and autoimmune diseases and the usage of glitazones or anticoagulant therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: degludec arm<br>25 patients were discontinued their previous therapy and given metformin alone (2 g/day) for seven days. After seven days they were randomized to first receive IDeg-100 In phase one they received IDeg-100 and metformin for 12 weeks. Phase one was followed by a second wash-up period in which patients received metformin alone again for seven days. In phase two, which also lasted for 12 weeks, patients were switched from IDeg-100 to IGlar-300 (and metformin was continued). The initial dose of both insulins was 0.2 IU/kg. | Drug: Degludec<br>* treatment of DM and it's affect on Glycaemic Variability, Oxidative Stress, Arterial Stiffness and the Lipid Profiles<br>|
| Active Comparator: glargine arm<br>25 patients were discontinued their previous therapy and given metformin alone (2 g/day) for seven days. After seven days they were randomized to first receive IGlar-300 In phase one they received IGlar-300 and metformin for 12 weeks. Phase one was followed by a second wash-up period in which patients received metformin alone again for seven days. In phase two, which also lasted for 12 weeks, patients were switched from IGlar-300 to IDeg-100 (and metformin was continued). The initial dose of both insulins was 0.2 IU/kg. | Drug: Glargine U300<br>* treatment of DM and it's affect on Glycaemic Variability, Oxidative Stress, Arterial Stiffness and the Lipid Profiles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in glucose variability | Glucose variability will be assessed at the beginning and the end of each phase using 3-day 7-point SMBG and calculating coefficient of variation in % out of SMBG recordings | 3 months | 
| Changes from baseline in oxidative stress | Oxidative stress will be assessed at the beginning and the end of each phase by measuring thiol groups and hydroperoxides (d-ROM) in serum | 3 months | 
| Changes from baseline in arterial stiffness after treatment | Oxidative stress will be assessed at the beginning and the end of each phase by measuring augmentation index with SphygmoCor. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in total cholesterol | Total cholesterol concentration in mmol/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in triglycerides | Triglyceride concentration in mmol/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in LDL | Low density lipoprotein cholesterol concentration in mmol/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in HDL | High density lipoprotein cholesterol concentration in mmol/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in WBC | White blood count will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in RBC | Red blood count will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in platelets | Platelets count will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in hemoglobin | Hemoglobin concentration in g/L will be assessed in at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in hematocrit | Hematocrit in L/L will be assessed in at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in MCV | Medium cellular volume in fL will be assessed in at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in liver enzymes | ALT, AST and GGT concentration in U/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in LDH | Lactate dehydrogenase concentration in U/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in ALP | Alkaline phosphatase concentration in U/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 
| Changes from baseline in CRP | C-reactive protein concentration in mg/L will be assessed at the beginning and the end of each phase by the automatic analyzer and enzymatic laboratory kit | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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degludec, Diabetes mellitus type 2, glargine U300, glucose variability, lipids, arterial stiffness, oxidative stress