Clinical trial NCT02373865: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Diabetes Mellitus Type 2
Keywords: Diabetes mellitus type 2
nocturnal hypoglycemia
metformin monotherapy
Lead sponsor: GWT-TUD GmbH
Sponsor class: OTHER
First posted: 2015-02-27
Enrollment: 4
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Hypoglycemic Episodes (HE) Under Treatment With Sitagliptin Compared to Glimepiride
timeFrame: 12 weeks (at baseline and at EOT)
Secondary outcomes:
measure: Occurence and Number of Nocturnal Ventricular Arrhythmias
timeFrame: 12 weeks (at baseline and at EOT)
measure: Glycemic Variability (Profile) of Sitagliptin Compared to Glimepiride
timeFrame: 12 weeks (at baseline and at EOT)
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: GWT-TUD GmbH / Studienzentrum Hanefeld
Study officials:
affiliation: GWT-TUD GmbH
name: Markolf Hanefeld, Prof. Dr.
role: STUDY_DIRECTOR
References: