Empagliflozin in Post-Transplantation Diabetes Mellitus
Status:
Completed
Trial end date:
2018-05-31
Target enrollment:
Participant gender:
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.