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

Phase 4TerminatedNCT02373865

GWT-TUD GmbH4 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Diabetes Mellitus Type 2

Interventions

SitagliptinDRUG

Sitagliptin will be given in a daily dosage of 100 mg

GlimepirideDRUG

Glimepiride will be given in a starting daily dosage of 1 mg which will be adapted up to 6 mg

Sitagliptin-PlaceboDRUG

Sitagliptin-Placebo will be given additional to Glimepiride (blinded). It will be given in a daily dosage of 100 mg

Eligibility

Sex: ALLMin age: 40 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (1)

GWT-TUD GmbH / Studienzentrum Hanefeld

Dresden, Germany

Outcomes

Primary Outcomes

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.

Time frame: 12 weeks (at baseline and at EOT)

Secondary Outcomes

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)

Time frame: 12 weeks (at baseline and at EOT)

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)

Time frame: 12 weeks (at baseline and at EOT)

Data from ClinicalTrials.gov

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