Empagliflozin in Renal Transplant Recipients (EMPA-RenalTx)

Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Post-transplantation Diabetes Mellitus

This is a single-center, prospective, controlled, double-blind, randomized study. A total of 50 renal transplant recipients diagnosed with post-transplantation diabetes mellitus (PTDM) will be included more than 1 year after transplantation and randomized 1:1 to empagliflozin (Jardiance®) 10 mg or placebo once daily for 24 weeks. Patients with estimated glomerular filtration rate below 30 mL/min will be excluded. Oral glucose tolerance test, 72h continuous glucose monitoring (iPro™2), measurement of arterial stiffness, body composition (including visceral fat), 24h blood pressure and 24h urinary glucose excretion will be performed at baseline and after 24 weeks in addition to standard safety measurements. Two safety visits will be performed at week 8 and 16. All concomitant medication, diet and exercise will be kept stable during the study period. The objective of the present study is to answer whether empagliflozin safely and effectively improves glucose metabolism together with weight loss in renal transplant recipients with PTDM.

Empagliflozin tablets enclosed with red capsules (Capsugel AAEL) by Kragerø Tablettproduksjon AS for blinding purpose

Placebo tablets made by Kragerø Tablettproduksjon AS and enclosed with red capsules (Capsugel AAEL) for blinding purpose

The primary endpoint will be change from baseline in weighted mean glucose at week 24 compared to placebo. Each patient will perform continuous plasma glucose monitoring (CGM, iProTM2) for 72 hours at baseline and after 24 weeks.

Measurement of bone mineral density, using low dosage radiation (dual-energy X-ray absorptiometry (DEXA) scan) to assess the amount (grams) of mineral that are packed into a segment of bone

Body composition (visceral fat, metabolic measurement) will be determined using the software CoreScan (encore version 14.10, GE Healthcare) on the DEXA scans. This will allow us to analyze changes in body fat compartments to explain overall weight reduction

Pulse wave velocity, using a SphygmoCor device, measuring arterial stiffness will be performed in addition to pulse wave analysis evaluating the shape and amplitude of the aortic pulse wave

Renal function, defined as glomerular filtration rate (GFR), will be evaluated by creatinine and cystatin C-based estimated GFR using the chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Fasting plasma creatinine and Cystatin C will be drawn at the same time and analyses will be performed at the Hospital central laboratory

Trough levels of immunosuppressive drugs (tacrolimus); number of participants with abnormal laboratory values

Inclusion Criteria: Renal transplant recipient transplanted more than 1 year ago Stable renal function (<20% deviation in serum creatinine within last 2 months) Stable immunosuppressive therapy ≥3 months before inclusion Diagnosed with PTDM: (fasting plasma glucose ≥7.0 mmol/l and/or 2-hour plasma glucose ≥11.1 mmol/l following an oral glucose tolerance test) -Signed informed consent and expected cooperation of the patients Exclusion Criteria: Estimated GFR <30 ml/min/1.73 m2 Pregnant or nursing mothers Hypersensitivity to the active substance (IMP) or to any of the excipients Any reason why, in the opinion of the investigator, the patient should not participate

Lo C, Toyama T, Oshima M, Jun M, Chin KL, Hawley CM, Zoungas S. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients. Cochrane Database Syst Rev. 2020 Jul 30;8(8):CD009966. doi: 10.1002/14651858.CD009966.pub3.

Halden TAS, Kvitne KE, Midtvedt K, Rajakumar L, Robertsen I, Brox J, Bollerslev J, Hartmann A, Asberg A, Jenssen T. Efficacy and Safety of Empagliflozin in Renal Transplant Recipients With Posttransplant Diabetes Mellitus. Diabetes Care. 2019 Jun;42(6):1067-1074. doi: 10.2337/dc19-0093. Epub 2019 Mar 12.