Diastolic Dysfunction in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Examination of the effect of Linagliptin versus placebo on diastolic function in patients with type 2 diabetes mellitus and diastolic dysfunction as assessed by transthoracic echocardiography. Furthermore the effect on serum levels of NT-pro BNP as a biomarker of heart failure will be investigated.

Detailed Description
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Treatment: The Patients will receive Linagliptin 5 mg QD or placebo for a period of 6 months. The echocardiography and 24h RR measurement will be performed at baseline and 6 months after initiation of the therapy. The blood chemistry (Glucose, HbA1c, BNP) will be evaluated at baseline as well as 3 and 6 months after initiation of the therapy.

Official Title
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Effect of Linagliptin Therapy on Myocardial Diastolic Function in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus Type 2 (T2DM), Left Ventricular Diastolic Dysfunction

Intervention / Treatment
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* Drug: Linagliptin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes mellitus Type 2 Age > 50 years HbA1c > 7% Left ventricular diastolic dysfunction determined by echocardiography as average E/é ≥13 or average E/é≥8 and LA volume ≥34ml/m2 Stable anti-diabetic medication for the last 6 weeks which should include a maximal tolerated dose of metformin (unless contraindication or intolerance to metformin does exist). Indication to increase anti-diabetic medication as judged by the investigator Written informed consent prior to study participation Exclusion Criteria: Diabetes mellitus type 1 Echocardiography: decreased left ventricular systolic function, ejection fraction (EF) <45% regional wall motion abnormalities hypertrophic cardiomyopathy (septum >15mm) severe valvular dysfunction Uncontrolled hypertension Atrial fibrillation Obstructive sleep apnea syndrome Use of DPP-4 Inhibitor (Dipeptidyl-peptidase IV Inhibitor), GLP 1 agonists, Thiazolindinedione Kidney disease CKD 4 and more (GFR < 30 ml/min/1.73) Liver disease (ALT or AST > 3 times the upper limit of norm) or known liver cirrhosis Active malignant disease HbA1c > 8.5% Recent (<3 months) clinically significant coronary or cerebral vascular event Pregnant females as determined by positive [serum or urine] hCG test at Screening or prior to dosing. Participants of child-bearing age should use adequate contraception as defined in the study protocol. Lactating females The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication. The subject received an investigational drug within 30 days prior to inclusion into this study The subject has any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study The subject is unwilling or unable to follow the procedures outlined in the protocol The subject is mentally or legally incapacitated

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Linagliptin<br>Linagliptin 5 mg (tablets) once daily for 6 month | Drug: Linagliptin<br> <br> * Other names: Trade name Trajenta® by Boehringer Ingelheim (BI) Pharma GmbH & Co KG, Biberach, Germany;|
| Placebo Comparator: Placebo<br>Placebo (tablets) once daily for 6 month | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular diastolic function | Change in left ventricular diastolic function between baseline and after 6 month as determined by 2D and novel 3D parameter global Strain Rate E Change in left ventricular diastolic function between baseline and after 6 month as determined by standardized parameter E/é and left atrial (LA) volume | baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum NT-pro BNP levels | Change in serum NT-pro BNP levels | baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T2DM, diastolic dysfunction