Please select the eligibility criteria that correspond to the clinical trial below.
Title: Empagliflozin in Post-Transplantation Diabetes Mellitus
Brief Summary: RELEVANCE:

Up to 50% of patients without previously known disorders of glucose metabolism develop posttransplantation diabetes mellitus (PTDM) after renal transplantation, which is associated with cardiovascular events. Although PTDM is triggered by immunosuppressive agents (calcineurin inhibitors, glucocorticoids), there is consensus against switching patients from potent tacrolimus to the less diabetogenic cyclosporin. Full-blown PTDM must therefore be treated aggressively. Empagliflozin inhibits sodium-glucose cotransporter 2 in the proximal tubule of the kidney and dramatically reduced cardiovascular risk in type 2 diabetics in a recent randomized trial. Especially in diabetics with impaired renal function, empagliflozin was safe, well tolerated, and effective against hyperglycemia and against high blood pressure. Data on SGLT2 inhibition after transplantation are completely lacking. Therefore, the potential antidiabetic of choice is currently withheld from the vulnerable PTDM population.

METHODS, STUDY DESIGN:

Prospective, single-center, non-inferiority study. Inclusion criteria: PTDM (antidiabetic therapy ≥6 months, based on prior 2-h BG ≥200 mg/dL, fasting BG ≥125 mg/dL (2 times) or HbA1c ≥6.5%); stable renal allograft function \>6 months; eGFR ≥30 mL/min/1.73m2. Most important exclusion criteria: type 1 and 2 diabetes; insulin demand \>40 IU/day; HbA1c \>8.5%. After study inclusion, patients will record 4 weeks of 4-times daily BG measurements before undergoing an OGTT, lab work and urine analysis (including ketones, urinary culture). Empagliflozin (10 mg) will be started and insulin discontinued within 3 days. Patients will be asked to perform urinary dipstick tests at home (i.e. ketones), and to continue recording BG. Study visits at 2 and 4 weeks (second OGTT + lab work (as above)). If control over hyperglycemia is insufficient, insulin therapy will be added back, otherwise study patients remain on empagliflozin monotherapy for 1 year. Statistics will include the paired t-test.


Options:
A: Inclusion Criteria:

* Renal transplant recipients more than 1 year post transplant with stable renal function (less than 20% deviation in serum creatinine within the last 2 months) and stable prednisolone dose (maximum 5 mg/day) the last three months before inclusion
* Diagnose of PTDM on standard clinical follow-up performed 8 weeks and 1 year post transplant at OUS-Rikshospitalet (fasting plasma glucose ≥ 7.0 mmol/l and/or 2-hour plasma glucose ≥ 11.1 mmol/l following an oral glucose tolerance test) OR
* Non-diabetic renal transplant recipients with a normal glucose tolerance test (control group)
* \> 18 years of age
* BMI 18.5-29.9 kg/m2
* Signed informed consent

Exclusion Criteria:

* Severe liver disease
* Pancreatitis (chronic or acute), previous bowel resection, inflammatory bowel disease, malignancy (previous or actual)
* Estimated GFR \< 25 ml/min/1.73 m2
* Pregnant or nursing mothers
B: Inclusion Criteria: - Type 2 diabetes - Age min. 50 years at screening and concomitant cardiovascular, cerebrovascular or peripheral vascular disease or chronic renal failure or chronic heart failure OR age min. 60 years at screening and other specified risk factors of cardiovascular disease - HbA1c: 7.0% or above - Anti-diabetic drug naive or treated with one or more oral anti-diabetic drugs (OADs) or treated with human NPH insulin or long-acting insulin analogue or premixed insulin, alone or in combination with OAD(s) Exclusion Criteria: - Type 1 diabetes - Use of a glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide or other) or pramlintide or any dipeptidyl peptidase 4 (DPP-4) inhibitor within the 3 months prior to screening (trial start) - Use of insulin other than human NPH insulin or long-acting insulin analogue or premixed insulin within 3 months prior to screening. Short-term use of other insulin during this period in connection with intercurrent illness is allowed, at Investigator's discretion
C: Inclusion Criteria:

* adult patients
* diabetic
* end stage renal disease undergoing cadaveric renal transplant

Exclusion Criteria:

* enrolled in concurrent study to test impact of a drug on graft function after transplant
D: Inclusion Criteria:

* Diagnosed PTDM defined as: A transplant patient requiring antidiabetic therapy, based on a previous 2-hour plasma glucose level ≥ 200 mg/dL in the OGTT (75mg glucose), based on previous blood glucose levels ≥ 200 mg/dL during random controls or based on fasting glucose levels ≥ 125 mg/dL twice or HbA1c ≥ 6.5%
* Stable graft function for more than 6 months post transplantation (eGFR ≥ 30 ml/min/1.73m2)
* At least 6 months of standard of care antidiabetic therapy (usually basal insulin) for PTDM

Exclusion Criteria:

* Age\< 18 years
* Patients with prior history of type 1 or type 2 diabetes
* Pregnancy
* Severe renal impairment (GFR \< 30 mL/min./1.73 m2)
* Severe blood glucose elevation with the need for therapy with insulin \> 40 IU/day or HbA1c \>8.5%

Answer: D