Effect of Insulin Degludec Versus Insulin Glargine on Glycemic Variability in Patients With Type 2 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
Type 2 diabetes mellitus (T2DM) is characterized by wide fluctuations of glucose. The long-acting insulin has showed to improve glycemic variability however the behavior of insulin glargine versus insulin degludec is unknown.

Detailed Description
-----------------
Cross-over, double dummy, randomized, clinical trial was carried out. The sample size was calculated using the formula for clinical trials of mean differences with an n of 6 patients per group was obtained. Patients between 30 and 65 years of age will be included with T2DM, without hyperglycemic drugs, hemoglobin A1c (A1C) 6.5 to 11.0 % and with written signature consent. They were assigned randomly by sealed envelope either to received insulin Degludec (Novo Nordisk A/S. Bagsvaerd, Denmark) or insulin Glargine (Sanofi-Aventis Deutschland GmbH. Frankfurt, Germany) [10 international units (IU) subcutaneous (SC) every 24 hours for six days], patients who were administered initially insulin Degludec corresponded then insulin Glargine and vice versa, with a washout period of 14 days between each intervention. The clinical findings and laboratory tests included a metabolic profile and biosafety, which will be made at baseline. Body weight, body mass index and blood pressure were performed during the initial visit, likewise, interstitial glucose concentrations by ambulatory continuous glucose monitoring system (Guardian®, Medtronic MiniMed, Northridge), through which the mean amplitude of glucose excursions (MAGE) and area under the curve of glucose were calculated, which served to assess the glycemic variability. Adverse events and adherence to treatment are documented. Statistical analysis: Mann-Whitney U test, Chi2, Fisher exact test. It is considered with significance at p <0.05.

Official Title
-----------------
Effect of the Administration of Insulin Degludec Versus Insulin Glargine on Glycemic Variability in Patients With Type 2 Diabetes Mellitus Drug-naïve

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: Insulin Degludec
* Drug: Insulin Glargine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with T2DM without treatment for at least 3 months Body mass index (BMI) from 25.0-34.9 kg/m2 Diagnosis of T2DM Fasting plasma glucose ≤300 mg/dL at the time of scrutiny A1C between 6.5 and 11% Written informed consent Exclusion Criteria: Women pregnant or breastfeeding Untreated thyroid disease and/or uncontrolled hypertension [≥150 systolic and diastolic ≥90] Consumption of oral agents or other medications or supplements with proven properties that modify the behavior of glucose. In the case of antihypertensives, these may be included if treatment was not modified previous 3 months and no change during the study. Total cholesterol >240 mg/dL Triglycerides ≥400 mg/dL Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) more than twice the normal range Glomerular filtration rate <60 mL/min [Cockcroft-Gault]

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Insulin Degludec - Insulin Glargine<br>Insulin Degludec 10 IU SC every 24 hours for 6 days Washout for 14 days Insulin Glargine 10 IU SC every 24 hours for 6 days | Drug: Insulin Degludec<br>* Insulin Degludec 10 IU SC every 24 hours for 6 days<br>* Other names: Tresiba ® (Novo Nordisk A/S. Bagsvaerd, Denmark);Drug: Insulin Glargine<br>* Insulin Glargine 10 IU SC every 24 hours for 6 days<br>* Other names: Lantus ® (Sanofi-Aventis Deutschland GmbH. Frankfurt, Germany);|
| Active Comparator: Insulin Glargine - Insulin Degludec<br>Insulin Glargine 10 IU SC every 24 hours for 6 days Washout for 14 days Insulin Degludec 10 IU SC every 24 hours for 6 days | Drug: Insulin Degludec<br>* Insulin Degludec 10 IU SC every 24 hours for 6 days<br>* Other names: Tresiba ® (Novo Nordisk A/S. Bagsvaerd, Denmark);Drug: Insulin Glargine<br>* Insulin Glargine 10 IU SC every 24 hours for 6 days<br>* Other names: Lantus ® (Sanofi-Aventis Deutschland GmbH. Frankfurt, Germany);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Variability: Mean Amplitude of Glucose Excursion (MAGE) | Mean amplitude of interstitial glucose excursions (MAGE) during the last 48 h of the ambulatory continuous glucose monitoring of 3 days (Guardian®, Medtronic MiniMed, Northridge); starting in the day 3 of the administration of insulin degludec or glargine | 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Variability: Area Under the Curve of Glucose | Area under the curve of glucose of the second day of continuous ambulatory glucose monitoring of 3 days (Guardian®, Medtronic MiniMed, Northridge) | Every 5 min for 24 hours on day 5 post-dose |