Use of Empagliflozin in Renal Transplant Recipients with Post Transplantation Diabetes Mellitus: Short Term Safety
Thea A S Halden1, Karsten Midtvedt1, Kine E Kvitne1, Anders Åsberg1,2, Anders Hartmann1,3, Trond G Jenssen1,4.
1Department of Transplantation Medicine, Section of Nephrology, Oslo University Hospital Rikshospitalet, Oslo, Norway; 2Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway; 3Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 4Metabolic and Renal Research Group, UiT, The Arctic University of Norway, Tromsø, Norway
Introduction: Development of post transplantation diabetes mellitus (PTDM) in renal transplant recipients (RTRs) is associated with increased cardiovascular risk and impaired patient survival. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) represent the most recent class of glucose-lowering drugs. The SGLT2i empagliflozin has been shown to improve both renal and cardiovascular outcomes in non-transplant patients with type 2 diabetes and established cardiovascular disease. We aim to evaluate whether empagliflozin (Jardiance®) safely and effectively improves glucose metabolism in RTRs with PTDM.
Materials and Methods: This is an ongoing investigator initiated, prospective, placebo controlled, double-blind, randomized study. A total of 50 RTRs diagnosed with PTDM will be included >1 year after transplantation and randomized 1:1 to empagliflozin 10 mg or placebo once daily for 24 weeks. Patients with eGFR <30 mL/min/1,73m2 will be excluded. The primary endpoint will be change in weighted mean glucose measured over 72h with continuous glucose monitoring (iProTM2). Safety in RTRs will also be investigated (ClinicalTrials.gov; NCT03157414).
Results: This interim analysis presents baseline and 24 weeks safety data for the presently 44 included patients with a mean age of 59.9 ±11.4 (33 males/11 females) studied 4.5 ±4.6 years after transplantation. Twenty-two patients have completed the study. No serious adverse events have been reported, but moderate hypoglycemia (plasma glucose between 2.0 and 3.9 mmol/L) is observed in four patients on concomitant sulphonylurea and/or DPP-4 inhibitor treatment. Two women have reported urinary tract infection and one of them developed genital fungal infection. No interactions with immunosuppressive drugs or other clinically relevant changes in blood parameters, including estimated GFR, have been observed. Pooled preliminary demographic and safety data are shown in Table 1.
|
BASELINE (N = 22) |
24 WEEKS (N = 22) |
P VALUE
|
|
|---|---|---|---|
| BMI (kg/m2) | 30.2 ± 5.6 | 29.9 ± 5.8 | 0.12 |
| HbA1c (%) | 7.3 ± 1.1 | 7.1 ± 1.0 | 0.30 |
| Fasting plasma glucose (mmol/L) | 8.0 ± 2.1 | 8.1 ± 2.2 | 0.78 |
| Systolic blood pressure (mmHg) | 138 ± 12 | 138 ± 15 | 0.96 |
| Diastolic blood pressure (mmHg) | 78 ± 7 | 78 ± 8 | 0.81 |
| Pulse Wave Velocity (m/s) | 11.1 ± 3.3 | 10.6 ± 2.9 | 0.37 |
| eGFR (ml/min/1.73 m2) | 61.6 ± 12.1 | 60.8 ± 12.2 | 0.51 |
Discussion: Since this study is double-blinded, there are currently no comparable results between groups.
Conclusion: Preliminary results indicate that the use of empagliflozin is safe in RTRs with PTDM.
The South-Eastern Regional Health Authority Norway .
