SGLT2 Inhibitor Use is Safe, Efficacious in Kidney Transplant Patients with Diabetes, Study Finds

Shirley Shuster, MD

New research from the Kingston Health Sciences Centre at Queen’s University has produced results in favor of SGLT2 inhibitor use in patients with diabetes who have undergone a kidney transplant.

A review of literature from 9 studies, results provide clinicians with what could be the largest overview yet detailing the efficacy and safety of SGLT2 inhibitor use in diabetic kidney transplant patients.

“Our literature review offers promising results suggesting the beneficial outcomes of SGLT2 inhibitor use in diabetic kidney transplant patients. Furthermore, its use did not result in significant adverse effects or complications,” said Shirley Shuster, MD, an internal medicine resident at Queen’s University, during her ENDO 2021 presentation.

In the last decade, knowledge surrounding the potential uses for SGLT2 inhibitors has expanded at a historic rate. With multiple agents within the class demonstrating benefits in heart failure and chronic kidney disease, Shuster and a team of colleagues sought to explore the efficacy and safety of these agents in kidney transplant patients with diabetes.

To do so, investigators designed their study as a literature review of studies assessing SGLT2 inhibitor use in patients with type 2 diabetes mellitus or new-onset diabetes after transplant (NODAT). Outcomes of interest for the analysis included changes in blood pressure, glycemic control, body weight, kidney function, proteinuria, and adverse events.

A search performed by investigators resulted in the identification of 9 articles for inclusion in their review, including 4 case series, 3 cohort studies, a case report, and a randomized clinical trial. In total, data from 144 patients was extracted from the articles. Most of the study cohort had NODAT (n=92) or type 2 diabetes mellitus (n=50).

Investigators noted the largest study was a prospective trial from Norway, which assessed empagliflozin in 44 patients. Empagliflozin (n=82) was the most commonly used SGLT2 inhibitor in the review, followed by canagliflozin (n=34), and dapagliflozin (n=28). All patients using SGLT2 inhibitors had an eGFR greater than 30 mL/min/1.73m2 and an HbA1c greater than 6.5% at baseline.

Upon analysis, investigators found SGLT2 inhibitor use in kidney transplant patients was associated with a small or non-significant reduction in blood pressure and modest improvements in glycemic control. Further analysis indicated SGLT2 inhibitor use was associated with reductions in insulin resistance and moderate-to-significant weight reductions. Investigators highlighted their review suggested SGLT2 inhibitor use did not negatively impact graft function and a single study indicated SGLT2 inhibitor use was associated with a reduction in proteinuria.

When assessing safety, investigators found urinary tract infection (n=13) was the most common adverse effect. Results of the safety analysis further supported the use of SGLT2 inhibitors in these patients. The most common adverse event in the review was urinary tract infection and investigators also pointed out there were no cases of diabetic ketoacidosis or development of new ischemic lower limb ulcerations or amputations seen with SGLT2 inhibitor use.

Based on the results of this study and previous research, Queens University will be conducting a prospective study in the future to further demonstrate the safety and efficacy of these agents in kidney transplant patients with diabetes.

“Our tertiary care center in Kingston, Ontario is launching a prospective study, which will assess the use of SGLT2 inhibitors in the kidney transplant population,” Shuster added.

This study, “Efficacy and Safety of SGLT2 Inhibitors in Diabetic Kidney Transplant Patients: Review of the Current Literature,” was presented virtually as part of ENDO 2021.