SGLT2 Inhibition and Left Ventricular Mass (EMPATROPHY)
Diabetes Mellitus Type 2
About this trial
This is an interventional treatment trial for Diabetes Mellitus Type 2
Eligibility Criteria
Inclusion Criteria:
- women and men ≥40 and <80 years of age
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%
- waist circumference ≥80 cm in women or ≥94 cm in men
- 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)
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
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
- signed written informed consent and willingness to comply with treatment and follow-up
- capability of understanding the investigational nature, potential risks and benefits of the clinical trial
Exclusion Criteria:
- diabetes mellitus type 1
- uncontrolled diabetes mellitus type 2 with fasting glucose > 13.3 mmol/l confirmed on a second day
- previous treatment with insulin, glucagon-like peptide-1 analogues, or pioglitazone during the last year before screening
- previous treatment with empagliflozin
- acute illness at screening or randomization according to judgement by the investigator or patient
- known or suspected hypersensitivity to empagliflozin, glimepiride or any excipients; known or suspected hypersensitivity to sulfonylureas or sulfonamides
- history of multiple severe hypoglycemic episodes
- any condition prohibiting MRI studies (e.g. metal implants, claustrophobia, body weight too high) including any suspected reaction after contrast agent application
- patient actively attempted to lose weight or experienced unintentional clinically significant weight loss during the last 3 months
- bariatric surgery or other gastrointestinal surgery procedures that induce chronic malabsorption
- treatment with any weight loss drug in the preceding 6 months
- planned significant changes of pre-study physical activity level during study participation
- heart failure New York Heart Association (NYHA) III - IV
- patients with known severe cardiovascular disease (e.g. myocardial infarction, unstable angina, stable coronary artery disease, stroke or transient ischemic attack)
- calculated glomerular filtration rate (eGFR) <60 ml/min/1,73 m2
- treatment with loop diuretics
- chronic diarrhea, any clinical signs of volume depletion or a haematocrit > 48 % (women) and > 53 % (men)
- history of severe volume depletion that required medical therapy
- chronic lower urinary tract infections (but not simple asymptomatic bacteriuria)
- known acute or chronic liver disease or screening liver enzymes > 3 x upper limit of normal (ULN)
- serum potassium < 3.6 or > 5.0 mmol/l
- glucose-6-phosphate dehydrogenase deficiency
- anemia of unknown origin
- pregnancy or lactation period
- treatment with systemic glucocorticoids during the last 3 months before screening
- chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs)
- changes in thyroid hormone dosage (stable doses of thyroid hormones for the last 3 months are acceptable)
- history of drug or alcohol abuse or current abuse
- 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
- medical history of cancer except for strictly localized tumors
- any medical or surgical intervention planned for the next 7 months after randomization not allowing study participation according to the investigator´s judgment
- current participation in any other clinical trial or participation in another clinical trial within 30 days before screening
Sites / Locations
- Hannover Medical School
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Empagliflozin
Glimepiride
25 mg/d empagliflozin + matching glimepiride placebo for 24 weeks.
2 or 4 mg/d glimepiride+ matching empagliflozin placebo for 24 weeks.