Intervention: Empagliflozin
Trial phase: Phase 1 | Phase 2
ATC code: A10BD19 | A10BD20 | A10BD27 | A10BK03
SMILES: OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(O[C@H]4CCOC4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 6
Group description: Individuals receive empagliflozin 25mg/day orally for 12 weeks

Empagliflozin 25 MG: Oral empagliflozin daily
Eligibility criteria:
Inclusion criteria:

Age 18 to 70 years old
Impaired glucose tolerance (two-hour plasma glucose 140-199 mg/dL) or impaired fasting glucose (100-125mg/dL) or HbA1c 5.7-6.4%
BMI ≥ 30 kg/M2
The ability to provide informed consent

Exclusion criteria:

Criteria Related to Medical Diagnoses/Conditions/Treatments:

Diabetes type 1 or type 2, as defined by a fasting plasma glucose of 126 mg/dL or greater, a two-hour plasma glucose of 200 mg/dL or greater, HbA1c ≥6.5%, or the use of anti-diabetic medication
Pregnancy or breast-feeding. Women of child-bearing potential will be required to have undergone tubal ligation or to be using an oral contraceptive or barrier methods of birth control
Cardiovascular disease such as myocardial infarction within six months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
Presence of implanted cardiac defibrillator or pacemaker
History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
History of pancreatitis or pancreatic surgery
History or presence of immunological or hematological disorders
Clinically significant gastrointestinal impairment that could interfere with drug absorption
History of advanced liver disease with cirrhosis
Individuals with an eGFR<45 mL/min/1.73 m2, where eGFR is determined by the four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 • Scr-1.154 • age-0.203 • (0.742 if female)
Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
Treatment with anticoagulants
Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
History of alcohol abuse (>14 per week for men and >7 per week for women) or illicit drug use
Treatment with any investigational drug in the one month preceding the study
Previous randomization in this trial
Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study

Inability to comply with the protocol in the opinion of the principal investigator, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study

Criteria Related to Known Adverse Effects of Drug:

Uncircumcised men or men with history of balanitis
History of urinary incontinence
History of recurrent (>3) episodes of vulvovaginitis per year, or severe symptoms
History of Fournier's gangrene
History of recurrent (≥3) UTIs per year or pyelonephritis
History of symptomatic hypotension or conditions predisposing to volume depletion
Known peripheral vascular disease, neuropathy, history of foot ulcers or lower limb amputations
Treatment with loop diuretics furosemide, torsemide, bumetanide, ethacrynic acid
Known or suspected allergy to trial medications, excipients, or related products
Contraindications to study medications, worded specifically as stated in the product's prescribing information