Type 2 Diabetes Mellitus
Conditions
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.
Interventions
DRUGInsulin Degludec
Insulin Degludec 10 IU SC every 24 hours for 6 days
DRUGInsulin Glargine
Insulin Glargine 10 IU SC every 24 hours for 6 days
Sponsors
University of Guadalajara
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
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 \[Cockcroft-Gault\]
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Variability: Mean Amplitude of Glucose Excursion (MAGE) | 2 days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Variability: Area Under the Curve of Glucose | Every 5 min for 24 hours on day 5 post-dose | Area under the curve of glucose of the second day of continuous ambulatory glucose monitoring of 3 days (Guardian®, Medtronic MiniMed, Northridge) |
Countries
Mexico
Participant flow
Pre-assignment details
Total number of patients: 12 in a crossover intervention. Interventions: 2. Washout period before the cross-over intervention. Protocol violations were detected at the end of the study in patients of both groups
Participants by arm
| Arm | Count |
|---|---|
| Insulin Total Group Total Group of Patients with Type 2 Diabetes mellitus | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Insulin Total Group |
|---|---|
| Age, Continuous | 44.1 years STANDARD_DEVIATION 8.8 |
| Alanine aminotransferase (ALT) | 41.6 mg/dl STANDARD_DEVIATION 25.9 |
| Aspartate aminotransferase (AST) | 25.8 mg/dl STANDARD_DEVIATION 11.3 |
| Body Mass Index | 32.1 kg/m^2 STANDARD_DEVIATION 2.5 |
| Creatinine | 0.7 mg/dl STANDARD_DEVIATION 0.2 |
| Diastolic Blood Pressure | 75.8 mmHg STANDARD_DEVIATION 6.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fasting Plasma Glucose | 181 mg/dl STANDARD_DEVIATION 59.8 |
| Hemoglobin A1c | 8.2 % of Hemoglobin A1c STANDARD_DEVIATION 1.4 |
| High-density lipoprotein-cholesterol (HDL-C) | 42.3 mg/dl STANDARD_DEVIATION 9.4 |
| Low-density lipoprotein-cholesterol (LDL-C) | 92.6 mg/dl STANDARD_DEVIATION 27.9 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 4 Participants |
| Systolic Blood Pressure | 114.8 mmHg STANDARD_DEVIATION 8.1 |
| Total Cholesterol | 174.8 mg/dl STANDARD_DEVIATION 29.5 |
| Triglycerides | 199.3 mg/dl STANDARD_DEVIATION 84.5 |
| Uric Acid | 4.6 mg/dl STANDARD_DEVIATION 1.4 |
| Weight | 80.5 kg STANDARD_DEVIATION 13.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 6 / 12 | 9 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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
Time frame: 2 days
Population: Comparison between both interventions. There are not baseline values of this measurements due to a design error. There were technical problems with the measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Degludec | Glycemic Variability: Mean Amplitude of Glucose Excursion (MAGE) | 75.2 mg/dl | Standard Deviation 38.9 |
| Insulin Glargine | Glycemic Variability: Mean Amplitude of Glucose Excursion (MAGE) | 68.5 mg/dl | Standard Deviation 47.4 |
p-value: 0.63Wilcoxon (Mann-Whitney)
Secondary
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)
Time frame: Every 5 min for 24 hours on day 5 post-dose
Population: Area Under the Curve of Glucose in a patient (Insulin Degludec group) could not be calculated. There are not baseline values of this measurements due to a design error. There were technical problems with the measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Degludec | Glycemic Variability: Area Under the Curve of Glucose | 46776 mg*h/dL | Standard Deviation 17860 |
| Insulin Glargine | Glycemic Variability: Area Under the Curve of Glucose | 46499 mg*h/dL | Standard Deviation 16971 |
p-value: 1Wilcoxon (Mann-Whitney)