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

• Sponsor: University of Guadalajara (Other)
• Overall Status: Completed
• CT.gov ID: NCT02680457
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Insulin Degludec; Drug: Insulin Glargine	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of the Administration of Insulin Degludec Versus Insulin Glargine on Glycemic Variability in Patients With Type 2 Diabetes Mellitus Drug-naïve
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Insulin Degludec - Insulin Glargine 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; Insulin Degludec 10 IU SC every 24 hours for 6 days; Other Names: Tresiba ® (Novo Nordisk A/S. Bagsvaerd, Denmark) ; Drug: Insulin Glargine; Insulin Glargine 10 IU SC every 24 hours for 6 days; Other Names: Lantus ® (Sanofi-Aventis Deutschland GmbH. Frankfurt, Germany)
Active Comparator: Insulin Glargine - Insulin Degludec 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; Insulin Degludec 10 IU SC every 24 hours for 6 days; Other Names: Tresiba ® (Novo Nordisk A/S. Bagsvaerd, Denmark) ; Drug: Insulin Glargine; Insulin Glargine 10 IU SC every 24 hours for 6 days; Other Names: Lantus ® (Sanofi-Aventis Deutschland GmbH. Frankfurt, Germany)

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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]

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara	Guadalajara	Jalisco	Mexico	44340

Sponsors and Collaborators

• University of Guadalajara

Investigators

• Principal Investigator: MANUEL GONZALEZ, PhD, University of Guadalajara

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Manuel González Ortiz, PhD, University of Guadalajara
• ClinicalTrials.gov Identifier: NCT02680457
• Other Study ID Numbers: CT-DG-140282-JLRN
• First Posted: Feb 11, 2016
• Last Update Posted: Sep 28, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine

Study Results

Participant Flow

Pre-assignment Detail	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

Arm/Group Title	Insulin Degludec - Insulin Glargine	Insulin Glargine - Insulin Degludec
Arm/Group Description	Insulin Degludec: 10 IU subcutaneous (SC) every 24 hours for 6 days Washout period for 14 days Insulin Glargine 10 IU SC every 24 hours for 6 days	Insulin Glargine: 10 IU subcutaneous (SC) every 24 hours for 6 days Washout period for 14 days Insulin Degludec 10 IU SC every 24 hours for 6 days
Period Title: Initial Intervention
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0
Period Title: Initial Intervention
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0
Period Title: Initial Intervention
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Insulin Total Group
Arm/Group Description	Total Group of Patients with Type 2 Diabetes mellitus
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.1 (8.8)
Sex: Female, Male (Count of Participants)
Female	8 66.7%
Male	4 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 100%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	80.5 (13.3)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	32.1 (2.5)
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	114.8 (8.1)
Diastolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	75.8 (6.4)
Hemoglobin A1c (% of Hemoglobin A1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% of Hemoglobin A1c]	8.2 (1.4)
Fasting Plasma Glucose (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	181 (59.8)
Uric Acid (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	4.6 (1.4)
Creatinine (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	0.7 (0.2)
Total Cholesterol (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	174.8 (29.5)
High-density lipoprotein-cholesterol (HDL-C) (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	42.3 (9.4)
Low-density lipoprotein-cholesterol (LDL-C) (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	92.6 (27.9)
Triglycerides (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	199.3 (84.5)
Aspartate aminotransferase (AST) (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	25.8 (11.3)
Alanine aminotransferase (ALT) (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	41.6 (25.9)

Outcome Measures

1. Primary Outcome

Title	Glycemic Variability: Mean Amplitude of Glucose Excursion (MAGE)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Insulin Degludec	Insulin Glargine
Arm/Group Description	Patients who received: Insulin Degludec: 10 IU SC every 24 hours for 6 days, from both arms of the study	Patients who received: Insulin Glargine: 10 IU SC every 24 hours for 6 days, from both arms of the study
Measure Participants	12	12
Mean (Standard Deviation) [mg/dl]	75.2 (38.9)	68.5 (47.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec, Insulin Glargine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.630
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Glycemic Variability: Area Under the Curve of Glucose
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Insulin Degludec	Insulin Glargine
Arm/Group Description	Patients who received: Insulin Degludec: 10 IU SC every 24 hours for 6 days, from both arms of the study	Patients who received: Insulin Glargine: 10 IU SC every 24 hours for 6 days, from both arms of the study
Measure Participants	11	12
Mean (Standard Deviation) [mg*h/dL]	46776 (17860)	46499 (16971)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec, Insulin Glargine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	From the beginning of the study until a month after the end of the intervention for each patient, an average of 2 months
Arm/Group Title	Insulin Degludec		Insulin Glargine
Arm/Group Description	Patients with Type 2 Diabetes mellitus Insulin Degludec: 10 IU SC every 24 hours for 6 days		Patients with Type 2 Diabetes mellitus Insulin Glargine: 10 IU SC every 24 hours for 6 days
All Cause Mortality
	Insulin Degludec		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Insulin Degludec		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Insulin Degludec		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/12 (50%)		9/12 (75%)
Endocrine disorders
Mild hypoglycemia	3/12 (25%)	3	2/12 (16.7%)	2
Gastrointestinal disorders
Flatulence	1/12 (8.3%)	1	0/12 (0%)	0
Nervous system disorders
Headache	1/12 (8.3%)	1	3/12 (25%)	3
Lower limb paresthesias	1/12 (8.3%)	1	4/12 (33.3%)	4

Limitations/Caveats

There were technical problems with the measurement of the outcomes. Design errors and protocol violations were detected at the end of the study. Therefore, the results are considered unreliable.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.