Efficacy and Safety of SGLT2 Inhibitors in Diabetic Kidney Transplant Patients: Review of the Current Literature

Introduction: SGLT2 inhibitors are oral hypoglycemic medications used in type 2 diabetes mellitus (T2DM). They act by blocking glucose and sodium reabsorption in the proximal renal tubules. In patients with T2DM and cardiovascular disease, SGLT2 inhibitors have been shown to improve glycemic control, promote weight loss, and reduce major adverse cardiovascular events (MACE). They have also been shown to have favorable renal outcomes in patients with chronic kidney disease (CKD) reducing albuminuria and progression to end-stage renal disease; however, all studies have excluded kidney transplant patients. The objective of this review was to determine the efficacy and safety of SGLT2 inhibitors in the kidney transplant population. Methods: We conducted a literature review to identify studies which assessed the use of SGLT2 inhibitors in kidney transplant patients with either T2DM or new onset diabetes after transplant (NODAT). The outcomes assessed included blood pressure, glycemic control, body weight, kidney function, proteinuria and complications. Results: Nine studies, which included 144 patients, were extracted for review. These included x4 case series, x3 cohort studies, x1 randomized control trial (RCT), and x1 case report. The largest study was a prospective RCT from Norway, which assessed empagliflozin versus placebo in 44 patients. Majority of patients had NODAT (n=92) or T2DM (n=50). All patients had estimated glomerular filtration rate (eGFR) >30mL/min/1.73m(2) and HbA1C >6.5%. The most commonly used SGLT2 inhibitors were empagliflozin (n=82), canagliflozin (n=34), and dapagliflozin (n=28). SGLT2 inhibitor use in kidney transplant patients was found to demonstrate a small or non-significant reduction in blood pressure, modest improvement in glycemic control and decrease in insulin resistance, and moderate-to-significant weight reduction. It also resulted in stable graft function and one study demonstrated a reduction in proteinuria. The most common adverse effect was urinary tract infection (n=13). There were no cases of diabetic ketoacidosis or development of new ischemic lower limb ulcerations or amputations. Conclusion: Our literature review suggests beneficial outcomes of SGLT2 inhibitor use in diabetic kidney transplant patients, with no significant adverse effects or complications. Given the limited evidence in this population, we are launching a prospective study in kidney transplant patients with either T2DM or NODAT, and with eGFR ≥30mL/min/1.73m(2), to assess the efficacy and safety of SGLT2 inhibitor use in this population. To our knowledge, this will be the first prospective study in Canada assessing SGLT2 inhibitor use in diabetic kidney transplant patients.