Sodium-glucose co-transporter 2 (SGLT2) inhibitors are safe for kidney transplant recipients (KTRs) with diabetes, and the therapies appear to improve renal outcomes, according to the findings of multiple studies presented at the 2022 American Transplant Congress in Boston, Massachusetts.
Studies demonstrated that KTRs treated with SGLT2 inhibitors experienced improvements in estimated glomerular filtration rate (eGFR) and proteinuria compared with those receiving standard of care.
Investigators from Virginia Commonwealth University Hospital in Richmond analyzed data from 118 KTRs with preexisting or new-onset type 2 diabetes who received treatment with SGLT2 inhibitors (90 who received empagliflozin, 22 canagliflozin, and 6 dapagliflozin).
At 6 and 12 months, the patients experienced a significant 2.95 and 4.09 mL/min/1.73 m2 increase in eGFR, investigator Gaurav Gupta, MD, reported in an oral presentation on behalf of his team. Over 12 months, they also experienced a significant 0.53 mg/mg mean decrease in urine protein to creatinine ratio and a significant mean 1.35 kg decline in body weight. The investigators observed no significant change in HbA1c at 12 months.
With regard to safety, 1 patient (0.01%) experienced euglycemic diabetic ketoacidosis and 18 (15%) had a symptomatic urinary tract infection. No patient had an amputation or had volume depletion.
Dr Gupta told listeners that “patients treated with SGLT2 inhibitors had a significant improvement in kidney function at 6 and 12 months post-initiation, along with an improvement in metabolic profiles.” The risk of adverse events with SGLT2 inhibitors in KTRs was comparable to published data from other cohorts, he said.
In a separate study of KTRs with type 2 diabetes, Jude Yagan, MD, from Hamed Al-Essa Organ Transplant Center in Kuwait, and colleagues compared 98 patients who received SGLT2 inhibitors for at least 3 months in addition to standard of care and a control arm of 96 patients who received standard of care alone. Standard of care included metformin, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and insulin. The groups were similar with respect to demographics and clinical characteristics.
Among patients with an eGFR above 90 and 45-59 mL/min/1.73 m2, the SGLT2 inhibitor group patients had an increase in eGFR at 12 months compared with a decrease in the control arm, Dr Yagan reported.
Use of SGLT2 inhibitors appeared to be safe, with no significant development of urinary tract and genital infections, graft dysfunction, or rejection, she reported.
The SGLT2 inhibitor group experienced a significant decrease in body mass index (BMI), whereas the control arm did not, Dr Yagan reported in an oral presentation.
The safety and positive effects of SGLT2 inhibitors in diabetic KTRs also emerged in a study by Tarek Mahmoud, MD, also from Hamed Al-Essa Organ Transplant Center in Kuwait, and colleagues. They analyzed data from 98 KTRs who received SGLT2 inhibitors and 41 who received GLP-1RAs. They compared these patients with a control group of 70 KTRs with diabetes who received only standard of care. KTRs were matched by age, sex, BMI, donor type, diabetes type, post-transplant duration, and immunosuppression. The patients were at least 3 months past transplant surgery, had stable kidney function at study inclusion, and had an eGFR of 25 mL/min/1.73 m2 or higher.
Overall, the 3 study arms displayed no significant difference in eGFR at 12 months. Among patients with an eGFR above 90 mL/min/1.73 m2, however, the SGLT2 inhibitor and GLP-1RA groups had a significantly improved eGFR compared with the control group.
Further, at 12 months, the albumin-to-creatinine ratio decreased significantly by a median of 28 mg/mmol in the SGLT2 inhibitor group and 20 mg/mmol in the GLP-1RA group, but increased by 3.5 mg/mmol in the control group.
The SGLT2 inhibitor and GLP-1RA groups experienced a significant 0.66% and 0.61% decrease in HbA1c, respectively, whereas HbA1c did not change significantly in the control group.
Dr Mahmoud concluded that SGLT2 inhibitors and GLP-1RAs appear to be safe and associated with good outcomes, noting that eGFR was maintained “despite fear of renal dysfunction in response to negative fluid balance and reduction in intraglomerular pressure with the use of SGLT2 inhibitors.”
He also stated, “Renal protection in the form of reduction of proteinuria was observed and matched the results seen in the outcome trials.”
Song C, Brown A, Winstead R, et al. Intermediate term outcomes of SGLT2 inhibitors among diabetic kidney transplant recipients. Presented at: ATC 2022, June 4-8, 2022. Abstract 30.
Yagan J, Mahmoud TS, Hasan A, et al. Sodium-glucose co-transporter 2 inhibitors; short-term outcome in diabetic kidney transplant recipients. Presented at: ATC 2022, June 4-8, 2022. Abstract 24.
Mahmoud TS, Yagan J, Hasan A, et al. Outcomes of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in diabetic kidney transplant recipients. Presented at: ATC 2022, June 4-8, 2022. Abstract 29.