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

Diabetes Mellitus Type 2 Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02373865
• Other study ID #: DIA-2-REDESIGN
• Status: Terminated
• Phase: Phase 4
• Start date: September 2015
• Est. completion date: January 2017

Study information

• Verified date: October 2018
• Source: GWT-TUD GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 2
• Diabetes Mellitus, Type 2
• Hypoglycemia

Intervention

Drug:
• Sitagliptin
Sitagliptin will be given in a daily dosage of 100 mg
• 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
• 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

Locations

Country	Name	City	State
Germany	GWT-TUD GmbH / Studienzentrum Hanefeld	Dresden

Sponsors (1)

Lead Sponsor	Collaborator
GWT-TUD GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 weeks (at baseline and at EOT)
Secondary	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)	12 weeks (at baseline and at EOT)
Secondary	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)	12 weeks (at baseline and at EOT)