Risk of Nocturnal Hypoglycemia and Arrhythmias With Sitagliptin Versus Glimepiride in Patients With Type 2 Diabetes
Primary Purpose
Diabetes Mellitus Type 2
Status
Terminated
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Sitagliptin
Glimepiride
Sitagliptin-Placebo
Glimepiride-Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus Type 2 focused on measuring Diabetes mellitus type 2, nocturnal hypoglycemia, metformin monotherapy
Eligibility Criteria
Inclusion Criteria:
- type 2 diabetes
- age 40-80 years
- stable dose of ≥ 1500 mg metformin or maximal tolerated dose of metformin for > 6 weeks
- HbA1c ≥ 7 % - ≤ 9.0% for age < 65 years and ≥ 7.5 % - ≤ 9.0% for age ≥ 65 years
- able and trained to perform SMBG
- the informed consent form must be signed before any study specific tests or procedures are done
- ability to understand and follow study-related instructions
Exclusion Criteria:
- Type 1 diabetes
- previous treatment with insulin, GLP1 analogues and SU in < 6 month
- HbA1c > 9 % or FPG > 15 mmol/l at randomization
- renal impairment with eGFR < 60 ml/min
- medical history of severe hypoglycemia defined as necessity of medical assistance in < 1 year
- major cardiovascular event (MACE) in medical history < 6 months
- preexisting atrial fibrillation, , AV block ≥II degree, pace-maker, implanted defibrillator
- major cardiovascular event in medical history < 6 months
- heart failure NYHA ≥ III
- contraindications to glimepiride and sitagliptin or to any excipients according to product information
- severe cognitive deficits
- Patients who are disable to read and understand informative aspects of the trial
- Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s)
- Inability to comply with study procedures
- Pregnant or breast-feeding woman and woman without adequate method of contraception
Sites / Locations
- GWT-TUD GmbH / Studienzentrum Hanefeld
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A
Arm B
Arm Description
Patients receiving Sitagliptin 100 mg+ Glimepiride-placebo (adapted dosage)
Glimepiride (adapted dosage) + Sitagliptin 100 mg Placebo
Outcomes
Primary Outcome Measures
Number of Hypoglycemic Episodes (HE) Under Treatment With Sitagliptin Compared to Glimepiride
measurement of hypoglycemic episodes including event duration at baseline and EOT after 12 weeks of treatment and measurement of time spent below critical values for hypoglycemic episodes are the primary objectives of this study. We will calculate overall episodes/time (5 days) and nocturnal episodes.
Secondary Outcome Measures
Occurence and Number of Nocturnal Ventricular Arrhythmias
measurement of nocturnal ventricular arrhythmias at baseline and EOT (after 12 weeks of treatment) - per patient, couplets per patient, triplets per patient)
Glycemic Variability (Profile) of Sitagliptin Compared to Glimepiride
The glycemic profile is defined as the area under the glucose-timeprofile obtained by continuous glucose monitoring (5 days baseline and 5 days after 12 weeks of each treatment)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02373865
Brief Title
Risk of Nocturnal Hypoglycemia and Arrhythmias With Sitagliptin Versus Glimepiride in Patients With Type 2 Diabetes
Official Title
Randomized Double Blind Parallel Design Study Comparing Risk of Nocturnal Hypoglycemia and Critical Arrhythmia With Sitagliptin Versus Glimepiride in Patients With Type 2 Diabetes Insufficiently Controlled With Metformin Monotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Terminated
Why Stopped
Premature termination due to insufficient patient recruitement..
Study Start Date
September 2015 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GWT-TUD GmbH
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This exploratory double blind randomized active controlled study is designed to assess the effects of a treatment with therapeutical dosage of sitagliptin versus therapeutical dosage of glimepiride as add on therapy in patients with diabetes mellitus type 2 (T2DM) patients inadequately controlled on metformin monotherapy.
Detailed Description
Type 2 Diabetes is associated with an increased cardiovascular morbidity and mortality. Among patients insufficiently controlled with metformin multimorbidity and polypharmacy is common that makes the patients frail for cardiovascular complications related to hypoglycemic events.
This exploratory double blind randomized active controlled study is designed to assess the effects of a treatment with therapeutical dosage of sitagliptin versus therapeutical dosage of glimepiride as add on therapy in patients with T2DM patients inadequately controlled on metformin monotherapy.
Examinations will be performed as a 5 day recording of subcutaneous glucose concentration (CGMS) and holder ECG (AMEDTEC) at baseline and after a 12 weeks treatment with sitagliptin or glimepiride as active comparators used in combination with metformin.
With recording of nocturnal hypoglycemia and arrhythmias it is aimed to evaluate favorable glycemic profile under treatment with sitagliptin compared to glimepiride. The primary objective is risk of serious HE for both drugs.
The glycemic profile of sitagliptin as add-on therapy to metformin seems to be favorable compared to sulfonylureass such as glimepiride. Treatment with sitagliptin as add-on to metformin therapy causes less glycemic fluctuations and may be associated with lower oxidative stress and down regulation of low grade inflammation. This hypothesis will be tested as an explorative double blind study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus Type 2
Keywords
Diabetes mellitus type 2, nocturnal hypoglycemia, metformin monotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Patients receiving Sitagliptin 100 mg+ Glimepiride-placebo (adapted dosage)
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Glimepiride (adapted dosage) + Sitagliptin 100 mg Placebo
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Intervention Description
Sitagliptin will be given in a daily dosage of 100 mg
Intervention Type
Drug
Intervention Name(s)
Glimepiride
Intervention Description
Glimepiride will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg
Intervention Type
Drug
Intervention Name(s)
Sitagliptin-Placebo
Intervention Description
Sitagliptin-Placebo will be given additional to Glimepiride (blinded). It will be given in a daily dosage of 100 mg
Intervention Type
Drug
Intervention Name(s)
Glimepiride-Placebo
Intervention Description
Glimepiride-Placebo will be given additional to Sitagliptin (blinded). It will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg
Primary Outcome Measure Information:
Title
Number of Hypoglycemic Episodes (HE) Under Treatment With Sitagliptin Compared to Glimepiride
Description
measurement of hypoglycemic episodes including event duration at baseline and EOT after 12 weeks of treatment and measurement of time spent below critical values for hypoglycemic episodes are the primary objectives of this study. We will calculate overall episodes/time (5 days) and nocturnal episodes.
Time Frame
12 weeks (at baseline and at EOT)
Secondary Outcome Measure Information:
Title
Occurence and Number of Nocturnal Ventricular Arrhythmias
Description
measurement of nocturnal ventricular arrhythmias at baseline and EOT (after 12 weeks of treatment) - per patient, couplets per patient, triplets per patient)
Time Frame
12 weeks (at baseline and at EOT)
Title
Glycemic Variability (Profile) of Sitagliptin Compared to Glimepiride
Description
The glycemic profile is defined as the area under the glucose-timeprofile obtained by continuous glucose monitoring (5 days baseline and 5 days after 12 weeks of each treatment)
Time Frame
12 weeks (at baseline and at EOT)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
type 2 diabetes
age 40-80 years
stable dose of ≥ 1500 mg metformin or maximal tolerated dose of metformin for > 6 weeks
HbA1c ≥ 7 % - ≤ 9.0% for age < 65 years and ≥ 7.5 % - ≤ 9.0% for age ≥ 65 years
able and trained to perform SMBG
the informed consent form must be signed before any study specific tests or procedures are done
ability to understand and follow study-related instructions
Exclusion Criteria:
Type 1 diabetes
previous treatment with insulin, GLP1 analogues and SU in < 6 month
HbA1c > 9 % or FPG > 15 mmol/l at randomization
renal impairment with eGFR < 60 ml/min
medical history of severe hypoglycemia defined as necessity of medical assistance in < 1 year
major cardiovascular event (MACE) in medical history < 6 months
preexisting atrial fibrillation, , AV block ≥II degree, pace-maker, implanted defibrillator
major cardiovascular event in medical history < 6 months
heart failure NYHA ≥ III
contraindications to glimepiride and sitagliptin or to any excipients according to product information
severe cognitive deficits
Patients who are disable to read and understand informative aspects of the trial
Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s)
Inability to comply with study procedures
Pregnant or breast-feeding woman and woman without adequate method of contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Markolf Hanefeld, Prof. Dr.
Organizational Affiliation
GWT-TUD GmbH
Official's Role
Study Director
Facility Information:
Facility Name
GWT-TUD GmbH / Studienzentrum Hanefeld
City
Dresden
ZIP/Postal Code
01307
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Risk of Nocturnal Hypoglycemia and Arrhythmias With Sitagliptin Versus Glimepiride in Patients With Type 2 Diabetes
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