SGLT2 Inhibition and Left Ventricular Mass

• Status: Terminated
• Trial end date: 2017-09-27
• Target enrollment: 0
• Participant gender: All

Summary

Patients with type 2 diabetes mellitus are exposed to an excessive heart failure risk secondary to left ventricular hypertrophy and impaired diastolic filling, a condition not addressed by currently available treatments. The abnormality results from obesity-induced volume overload, increased blood pressure, and myocardial fat accumulation. By improving metabolism, body weight, and blood pressure, Empagliflozin addresses the root causes of type 2 diabetes-associated myocardial disease. We will assess left ventricular mass, function, and lipid content in patients with type 2 diabetes mellitus using cardiac magnetic resonance imaging and spectroscopy as well as echocardiography before and after empagliflozin or glimepiride treatment. We expect to observe improvements in left ventricular mass, function, and fat content with empagliflozin. The results of the study will help to position empagliflozin as an antidiabetic agent with the added value of protecting the heart.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hannover Medical School
• Collaborators: Boehringer Ingelheim; Hannover Clinical Trial Center GmbH
• Treatments: Empagliflozin; Glimepiride

Criteria

Inclusion Criteria:

1. women and men ≥40 and <80 years of age

2. patients with type 2 diabetes mellitus on stable anti-diabetic treatment for the last 3 months; at screening the following treatment conditions are allowed:

• metformin + sulfonylurea with HbA1c ≥6.5% and ≤9.0%

• metformin monotherapy with HbA1c ≥7.5% and ≤ 9.0%

• metformin + dipeptidylpeptidase-IV inhibitor with ≥6.5% and ≤9.0%

3. waist circumference ≥80 cm in women or ≥94 cm in men

4. office blood pressure ≤150/95 mm Hg with a stable dose of a maximum of 4 antihypertensive medications for the last 3 months (24h ambulatory blood pressure measurement (ABPM) is allowed to check accuracy of office values; inclusion with 24h mean blood pressure ≤145/90 mm Hg is possible)

5. women without childbearing potential defined by:

• at least 6 weeks after surgical sterilization by bilateral tubal ligation or bilateral oophorectomy

• hysterectomy

• ≥ 50 years and in postmenopausal state > 1 year

• < 50 years and in postmenopausal state > 1 year with serum follicle-stimulating Hormone (FSH) > 40 IU/l and serum estrogen < 30 ng/l or a negative estrogen test, both at screening

6. women of childbearing potential with a negative serum pregnancy test at screening who agree to meet one of the following criteria from the time of screening, during the study and for a period of 4 days following the last administration of study medication:

• correct use of reliable contraception methods. The following are acceptable:

hormonal contraceptives (combined oral contraceptives, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release), intrauterine device (IUD/IUS) or a double barrier method, e.g. condom and occlusive cap (diaphragm or cervical/vault caps) with spermicide (foam, gel, film, cream or suppository)

• true abstinence (periodic abstinence and withdrawal are not acceptable methods of contraception)

• sexual relationship only with female partners

• sterile male partners

7. signed written informed consent and willingness to comply with treatment and follow-up

8. capability of understanding the investigational nature, potential risks and benefits of the clinical trial

Exclusion Criteria:

1. diabetes mellitus type 1

2. uncontrolled diabetes mellitus type 2 with fasting glucose > 13.3 mmol/l confirmed on a second day

3. previous treatment with insulin, glucagon-like peptide-1 analogues, or pioglitazone during the last year before screening

4. previous treatment with empagliflozin

5. acute illness at screening or randomization according to judgement by the investigator or patient

6. known or suspected hypersensitivity to empagliflozin, glimepiride or any excipients; known or suspected hypersensitivity to sulfonylureas or sulfonamides

7. history of multiple severe hypoglycemic episodes

8. any condition prohibiting MRI studies (e.g. metal implants, claustrophobia, body weight too high) including any suspected reaction after contrast agent application

9. patient actively attempted to lose weight or experienced unintentional clinically significant weight loss during the last 3 months

10. bariatric surgery or other gastrointestinal surgery procedures that induce chronic malabsorption

11. treatment with any weight loss drug in the preceding 6 months

12. planned significant changes of pre-study physical activity level during study participation

13. heart failure New York Heart Association (NYHA) III - IV

14. patients with known severe cardiovascular disease (e.g. myocardial infarction, unstable angina, stable coronary artery disease, stroke or transient ischemic attack)

15. calculated glomerular filtration rate (eGFR) <60 ml/min/1,73 m2

16. treatment with loop diuretics

17. chronic diarrhea, any clinical signs of volume depletion or a haematocrit > 48 % (women) and > 53 % (men)

18. history of severe volume depletion that required medical therapy

19. chronic lower urinary tract infections (but not simple asymptomatic bacteriuria)

20. known acute or chronic liver disease or screening liver enzymes > 3 x upper limit of normal (ULN)

21. serum potassium < 3.6 or > 5.0 mmol/l

22. glucose-6-phosphate dehydrogenase deficiency

23. anemia of unknown origin

24. pregnancy or lactation period

25. treatment with systemic glucocorticoids during the last 3 months before screening

26. chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs)

27. changes in thyroid hormone dosage (stable doses of thyroid hormones for the last 3 months are acceptable)

28. history of drug or alcohol abuse or current abuse

29. psychosomatic or psychiatric diseases requiring hospitalization during the last 12 months; ongoing treatment with one tricyclic or selective serotonin re-uptake Inhibitor (SSRI) antidepressant drug at a stable dose since the last 3 months is acceptable except for fluoxetine

30. medical history of cancer except for strictly localized tumors

31. any medical or surgical intervention planned for the next 7 months after randomization not allowing study participation according to the investigator´s judgment

32. current participation in any other clinical trial or participation in another clinical trial within 30 days before screening