SGLT2 inhibition with empagliflozin in patients with type 2 diabetes mellitus: Influences on left ventricular mass, function, and lipid content of myocardium (EMPATROPHY)

Phase 1

• Conditions: Patients with type 2 diabetes mellitus on background metformin treatment.; MedDRA version: 18.0Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2014-003313-28-DE
• Lead Sponsor: Hannover Medical School

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-06-18
• Last Update Posted: 16 May 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

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 + DPP-IV inhibitor withHbA1c = 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 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 ß-hCG 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

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, GLP-1 analogues, or pioglitazone during the last year before screening
4. previous participation in another empagliflozin trial
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)
9. patient akctively 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 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. eGFR <60 ml/min/1,73 m²
16. treatment with loop diuretics
17. acute or chronic diarrhea, any clinical signs of volume depletion or a hematocrit > 48 % (women) and > 53 % (men)
18. chronic lower urinary tract infections
19. known acute or chronic liver disease or screening ALT or AST > 3 x ULN
20. serum potassium < 3.6 or > 5.0 mmol/l
21. glucose-6-phosphate dehydrogenase deficiency
22. anemia of unknown origin
23. pregnancy or lactation period
24. treatment with systemic glucocorticoids during the last 3 months before screening
25. chronic treatment with NSAIDs
26. changes in thyroid hormone dosage (stable doses of thyroid hormones for the last 3 months are acceptable)
27. history of drug or alcohol abuse or current abuse
28. psychosomatic or psychiatric diseases requiring hospitalization during the last 12 months; ongoing treatment with one tricyclic or SSRI antidepressant drug at a stable dose since the last 3 months is acceptable
29. medical history of cancer except for strictly localized tumors
30. any planned medical or surgical intervention planned for the next 7 months after randomization that does not allow study participation according to the investigator´s judgment
31. current participation in any other clinical trial or participation in another clinical trial within 30 days before screening

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: • changes in cardiac dimensions, function, and metabolism<br>• changes in glucose homeostasis<br>• changes in body composition<br>• changes in ambulatory blood pressure<br>• changes in systemic and adipose tissue inflammatory markers and markers of insulin resistance<br>;Primary end point(s): Change in left ventricular mass determined by cardiac MRI as the difference between 24 weeks and baseline.;Timepoint(s) of evaluation of this end point: Week 24;Main Objective: To demonstrate that left ventricular mass is reduced with empagliflozin treatment compared to glimepiride treatment on top of stable metformin background medication.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • change in left ventricular end-systolic and end-diastolic volume (cMRI, 24 weeks – baseline)<br>• changes in left ventricular function (cMRI, 24 weeks – baseline)<br>• change in intramyocardial lipid content (cMR spectroscopy, 24 weeks – baseline)<br>• change in diastolic function (echocardiography, 24 weeks – baseline)<br>• change in HbA1c (24 weeks – baseline)<br>• change in fasting glucose and insulin (24 weeks – baseline)<br>• changes in body weight, waist circumference, and body fat mass (24 weeks – baseline)<br>• change in ambulatory blood pressure (24 weeks – baseline)<br>;Timepoint(s) of evaluation of this end point: Week 24