Risk of Nocturnal Hypoglycemia and Arrhythmias With Sitagliptin Versus Glimepiride in Patients With Type 2 Diabetes

• Sponsor: GWT-TUD GmbH (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02373865
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Type 2	Drug: Sitagliptin; Drug: Glimepiride; Drug: Sitagliptin-Placebo; Drug: Glimepiride-Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: Sep 1, 2015
• Actual Primary Completion Date: Jan 1, 2017
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Patients receiving Sitagliptin 100 mg+ Glimepiride-placebo (adapted dosage)	Drug: Sitagliptin; Sitagliptin will be given in a daily dosage of 100 mg; Drug: Glimepiride-Placebo; 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
Active Comparator: Arm B Glimepiride (adapted dosage) + Sitagliptin 100 mg Placebo	Drug: Glimepiride; Glimepiride will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg; Drug: Sitagliptin-Placebo; Sitagliptin-Placebo will be given additional to Glimepiride (blinded). It will be given in a daily dosage of 100 mg

Outcome Measures

Primary Outcome Measures

1. Number of Hypoglycemic Episodes (HE) Under Treatment With Sitagliptin Compared to Glimepiride [12 weeks (at baseline and at EOT)]

   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

1. Occurence and Number of Nocturnal Ventricular Arrhythmias [12 weeks (at baseline and at EOT)]

   measurement of nocturnal ventricular arrhythmias at baseline and EOT (after 12 weeks of treatment) - per patient, couplets per patient, triplets per patient)

2. Glycemic Variability (Profile) of Sitagliptin Compared to Glimepiride [12 weeks (at baseline and at EOT)]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GWT-TUD GmbH / Studienzentrum Hanefeld	Dresden		Germany	01307

Sponsors and Collaborators

• GWT-TUD GmbH

Investigators

• Study Director: Markolf Hanefeld, Prof. Dr., GWT-TUD GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GWT-TUD GmbH
• ClinicalTrials.gov Identifier: NCT02373865
• Other Study ID Numbers: DIA-2-REDESIGN
• First Posted: Feb 27, 2015
• Last Update Posted: Feb 27, 2019
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by GWT-TUD GmbH: Diabetes mellitus type 2; nocturnal hypoglycemia; metformin monotherapy
• Additional relevant MeSH terms: Diabetes Mellitus; Hypoglycemia; Diabetes Mellitus, Type 2; Sitagliptin Phosphate; Glimepiride

Study Results

Participant Flow

Recruitment Details	In the time period between the start of the clinical trial (march 2015 (approval of German competent authority) and the premature termination (Jan 2017) only 4 patients of originally planned 68 patients could be recruited. Recruitment period started at 09.11.2015 when first patient was enrolled into study.
Pre-assignment Detail	no pre-assignment details are available for this study

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients receiving Sitagliptin 100 mg+ Glimepiride-placebo (adapted dosage) Sitagliptin: Sitagliptin will be given in a daily dosage of 100 mg Glimepiride-Placebo: 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	Glimepiride (adapted dosage) + Sitagliptin 100 mg Placebo Glimepiride: Glimepiride will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg Sitagliptin-Placebo: Sitagliptin-Placebo will be given additional to Glimepiride (blinded). It will be given in a daily dosage of 100 mg
Period Title: Overall Study
STARTED	2	2
COMPLETED	2	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm A: Sitagliptin 100 mg+ Glimepiride-placebo (Adapted Dose)	Arm B: Glimepiride (Adapted Dose) + Sitagliptin 100 mg Placebo	Total
Arm/Group Description	Patients receiving Sitagliptin 100 mg+ Glimepiride-placebo (adapted dosage) Sitagliptin: Sitagliptin will be given in a daily dosage of 100 mg Glimepiride-Placebo: 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	Glimepiride (adapted dosage) + Sitagliptin 100 mg Placebo Glimepiride: Glimepiride will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg Sitagliptin-Placebo: Sitagliptin-Placebo will be given additional to Glimepiride (blinded). It will be given in a daily dosage of 100 mg	Total of all reporting groups
Overall Participants	2	2	4
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (2.82)	69 (9.89)	64 (6.35)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	2 100%	2 100%	4 100%
Region of Enrollment (participants) [Number]
Germany	2 100%	2 100%	4 100%

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

Due to an impeded recruitment of patients the study was terminated. Between start (March 2015) and premature termination (Jan 2017) only 4 patients could be recruited. The reason for "0" Participants Analyzed provided in the Analysis Population Description is intended to report that data were not reported due to the termination of the study.

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients receiving Sitagliptin 100 mg+ Glimepiride-placebo (adapted dosage) Sitagliptin: Sitagliptin will be given in a daily dosage of 100 mg Glimepiride-Placebo: 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	Glimepiride (adapted dosage) + Sitagliptin 100 mg Placebo Glimepiride: Glimepiride will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg Sitagliptin-Placebo: Sitagliptin-Placebo will be given additional to Glimepiride (blinded). It will be given in a daily dosage of 100 mg
Measure Participants	0	0

2. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

Due to an impeded recruitment of patients the study was terminated. Between start (March 2015) and premature termination (Jan 2017) only 4 patients could be recruited. The reason for "0" Participants Analyzed provided in the Analysis Population Description is intended to report that data were not reported due to the termination of the study.

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients receiving Sitagliptin 100 mg+ Glimepiride-placebo (adapted dosage) Sitagliptin: Sitagliptin will be given in a daily dosage of 100 mg Glimepiride-Placebo: 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	Glimepiride (adapted dosage) + Sitagliptin 100 mg Placebo Glimepiride: Glimepiride will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg Sitagliptin-Placebo: Sitagliptin-Placebo will be given additional to Glimepiride (blinded). It will be given in a daily dosage of 100 mg
Measure Participants	0	0

3. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

Due to an impeded recruitment of patients the study was terminated. Between start (March 2015) and premature termination (Jan 2017) only 4 patients could be recruited. The reason for "0" Participants Analyzed provided in the Analysis Population Description is intended to report that data were not reported due to the termination of the study.

Arm/Group Title	Arm A	Arm B
Arm/Group Description	Patients receiving Sitagliptin 100 mg+ Glimepiride-placebo (adapted dosage) Sitagliptin: Sitagliptin will be given in a daily dosage of 100 mg Glimepiride-Placebo: 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	Glimepiride (adapted dosage) + Sitagliptin 100 mg Placebo Glimepiride: Glimepiride will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg Sitagliptin-Placebo: Sitagliptin-Placebo will be given additional to Glimepiride (blinded). It will be given in a daily dosage of 100 mg
Measure Participants	0	0

Adverse Events

Arm/Group Title	Arm A: Sitagliptin 100 mg+ Glimepiride-placebo (Adapted Dose)		Arm B: Glimepiride (Adapted Dose) + Sitagliptin 100 mg Placebo
Arm/Group Description	Patients receiving Sitagliptin 100 mg+ Glimepiride-placebo (adapted dosage) Sitagliptin: Sitagliptin will be given in a daily dosage of 100 mg Glimepiride-Placebo: 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		Glimepiride (adapted dosage) + Sitagliptin 100 mg Placebo Glimepiride: Glimepiride will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg Sitagliptin-Placebo: Sitagliptin-Placebo will be given additional to Glimepiride (blinded). It will be given in a daily dosage of 100 mg
All Cause Mortality
	Arm A: Sitagliptin 100 mg+ Glimepiride-placebo (Adapted Dose)		Arm B: Glimepiride (Adapted Dose) + Sitagliptin 100 mg Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Serious Adverse Events
	Arm A: Sitagliptin 100 mg+ Glimepiride-placebo (Adapted Dose)		Arm B: Glimepiride (Adapted Dose) + Sitagliptin 100 mg Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Arm A: Sitagliptin 100 mg+ Glimepiride-placebo (Adapted Dose)		Arm B: Glimepiride (Adapted Dose) + Sitagliptin 100 mg Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)

Limitations/Caveats

Limitations of the study: deceleration of patient recruitment, break up of patient recruitment, descriptive reporting of patient characteristics of 4 enrolled patients (no statistically reliable results are available)

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.