Efficacy and Safety of Sglt-2 Inhibitors In Renal Allograft Recipients: an Open-Label, Single-Center Prospective Study.

Aim    To evaluate the safety and efficacy of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) inhibitor therapy in kidney transplant recipients (KTRs) with and without post-transplant diabetes mellitus (PTDM).Material and methods     KTRs (n=2146, with PTDM n=303, or 14%) who had undergone transplantation more than one year ago, with stable graft function (estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m2), after excluding patients with combined kidney and pancreas transplantation (n=57), type 1 diabetes mellitus (DM) (n=124), and type 2 DM diagnosed before kidney allotransplantation (KAT) (n=74), were prescribed SGLT-2i (empagliflozin 25 mg/day or dapagliflozin 10 mg/day; n=107), the rest of the KTRs (n=1784) did not receive SGLT-2i. After pseudo-randomization, two groups were formed and included in an open, single-center prospective study: an experimental group with SGLT-2i (n=78; with PTDM n=45) and a control group, without SGLT-2i (n=78; n=45 with PTDM). The groups were comparable in the PTDM duration and the period from KAT to inclusion in the study, as well as in clinical characteristics, including gender, age, history of acute myocardial infarction (AMI) before KAT, levels of glycated hemoglobin (HbA1c), systolic blood pressure (SBP) and diastolic blood pressure (DBP), GFR, microalbuminuria (MAU), blood uric acid concentration, blood lipid profile (total cholesterol (TC), low-density lipoproteins (LDL)), basal blood concentration (C0) of calcineurin inhibitors (CNI), and therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), statins, and metformin (p >0.05).Results     The relative risk (RR) of all-cause death in the experimental group was reduced by 60% compared with the control group (RR 0.40; 95% confidence interval (CI) 0.17-0.98 vs. RR 2.44; 95% CI 1.01-5.86; p=0.04). The RR of adverse coronary outcomes in the experimental group was reduced by 75% compared with the control group (RR 0.25; 95% CI 0.06-0.89 vs. 4.0; 95% CI 1.11-14.42; p=0.03). The RR of adverse renal outcomes in the experimental group was reduced by 72% compared with the control group (RR 0.28; 95% CI 0.09-0.85 vs. 3.50; 95% CI 1.16-10.49; p=0.02). In addition, in the experimental group, compared to the control group, the GFR decline was slower (-1.29±0.763 ml/min/1.73 m2/year vs. -3.33±0.767 ml/min/1.73 m2/year; p=0.047). Also, a pronounced advantage in the dynamic decline in GFR was observed throughout the entire study period (-3.10±1.73 ml/min/1.73 m2 vs. -7.87±1.87 ml/min/1.73 m2; p=0.040).Conclusion SGLT2i effectively reduce cardiovascular and renal mortality, the risk of adverse renal and coronary outcomes, and slow the progression of chronic kidney disease in KTRs, regardless of the presence of PTDM. A large-scale study evaluating the efficacy of SGLT2i in KTRs is warranted to formulate appropriate clinical recommendations.