Recently, SGLT2 inhibitors (SGLT2i) have been proven to provide cardiovascular and renal protection for patients with chronic kidney disease (CKD), effectively slowing renal function decline and reducing proteinuria and blood pressure, regardless of diabetes status.
However, in kidney transplant recipients (KTRs), concerns have arisen regarding potential drug interactions and adverse effects due to concurrent use of immunosuppressants. Research on this population has been limited.
This article examines the latest data from the GREAT-ASTRE study conducted in France to assess the efficacy and safety of SGLT2 inhibitors in kidney transplant recipients.
The GREAT-ASTRE study is a multicenter real-world study conducted across 13 kidney transplant centers in France, evaluating the safety and short-term efficacy of SGLT2 inhibitors in kidney transplant recipients. A total of 347 patients participated, with the majority (96.6%) receiving dapagliflozin.
The study population had an average age of 62.6 years, with males comprising 76.4% of participants. On average, patients began SGLT2 inhibitor treatment 6.7 years post-transplantation.
Diabetic patients accounted for 65.1% of the cohort, with most starting treatment more than a year after transplantation.
Initially, proteinuria levels were high, but after 3 months of SGLT2 inhibitor use, a significant reduction was observed (p<0.0001). This effect persisted at 6 months (p=0.0002), though no additional reduction was noted between months 3 and 6 (p=0.690).
Among diabetic patients, proteinuria also significantly decreased at 3 months (p=0.001) and remained statistically lower at 6 months (p=0.032). However, no substantial decrease was observed between months 3 and 6 (p=0.256).
Similarly, in non-diabetic patients, proteinuria significantly decreased at 3 months (p=0.0007). However, there was no statistically significant further reduction between months 3 and 6 (p=0.083).
These graphs illustrate that SGLT2 inhibitors can significantly reduce proteinuria in kidney transplant recipients, regardless of diabetes status. Notably, the treatment demonstrated a rapid onset of effect, which persisted for at least 6 months, making it clinically valuable.
A 64-year-old male, 7 years post-kidney transplantation, had a history of diabetes and hypertension. Despite post-transplant treatment, he continued to experience persistent proteinuria and uncontrolled hypertension. He was started on dapagliflozin.
At the beginning of treatment, his estimated glomerular filtration rate (eGFR) was 50 ml/min, daily proteinuria was 1200 mg, and blood pressure was 150/90 mmHg.
After 3 months on dapagliflozin, his proteinuria decreased to 800 mg, and his blood pressure improved to 140/85 mmHg. At 6 months, these benefits were maintained, with a slight reduction in eGFR to 48 ml/min, though without significant clinical implications. No adverse effects or drug interactions with immunosuppressants were reported.
Among the 347 patients in the GREAT-ASTRE study, 25.9% reported side effects, but severe adverse events were rare. The most common side effect was urinary tract infection (6.6%), while genital infections were minimal (0.6%).
The discontinuation rate due to side effects was 15.6%, primarily due to worsening graft function and infections.
Patients with severely impaired renal function (eGFR < 30 ml/min) exhibited a higher discontinuation rate, indicating the need for cautious prescribing in this subgroup.
The GREAT-ASTRE study found no clinically significant drug interactions between SGLT2 inhibitors and common immunosuppressants, such as calcineurin inhibitors (CNIs), mycophenolate mofetil, or steroids. Current evidence suggests that SGLT2 inhibitors can be safely used alongside immunosuppressive therapies.
Since this study was conducted over less than a year, long-term effects on graft survival, cardiovascular disease prevention, and mortality remain unknown. Additional long-term follow-up is necessary.
The GREAT-ASTRE research team has planned a 5-year follow-up study, which is expected to provide more definitive insights into the cardiovascular benefits and renal protection of SGLT2 inhibitors in kidney transplant patients.
The preliminary findings of the GREAT-ASTRE study suggest that SGLT2 inhibitors can be safely and effectively used in kidney transplant recipients with relatively preserved renal function. The drug demonstrated notable benefits in reducing proteinuria and improving blood pressure.
However, caution is required when prescribing SGLT2 inhibitors to patients with significantly impaired renal function (eGFR < 30 ml/min) due to a higher likelihood of treatment discontinuation.
To date, no clinically relevant drug interactions between SGLT2 inhibitors and immunosuppressants have been identified. Until further long-term data become available, periodic monitoring and cautious prescribing remain advisable.
L Maigret et al., Sodium-Glucose Cotransporter-2 Inhibitor in Diabetic and Nondiabetic Renal Transplant Recipients, Kidney International Reports, 2025, Volume 10, Pages 816–827. https://doi.org/10.1016/j.ekir.2024.11.033
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