Study the effect of sodium-glucose cotransporter-2 inhibition versus dipeptidyl peptidase-4 inhibition in diabetic kidney transplant recipients

Authors

Torki Alotaibi; Zakaria Alsayed; Ahmed Yahya; Mohamed Shaker; Mahmoud Khaled; Mohamed Emam; Mohamed Mostafa; Mohamed Hammad; Ahmed Deneawar; Mohamed Dahab; Nabil Elserwy; Ayman Maher; Mohamed Abdelmonem; Osama A. Gheith

Citation

Arab J Nephrol Transplant. 2026;8(3):105–113. doi: 10.4103/AJNT.AJNT_5_26

Abstract

Background Post‑transplant diabetes mellitus (PTDM) and pre‑existing type 2 diabetes significantly impact kidney transplant outcomes. While sodium‑glucose cotransporter‑2 inhibitors (SGLT2i) and dipeptidyl peptidase‑4 inhibitors (DPP‑4i) have demonstrated cardiorenal benefits in the general population, comparative data in kidney transplant recipients remain limited. Aim Therefore, this study aims to compare the effects of SGLT2i versus DPP4i on renal, cardiovascular, glycemic, and safety outcomes in diabetic kidney transplant recipients, addressing a critical evidence gap to inform optimal antidiabetic therapy selection in this high‑risk population. Patients and methods This observational cohort study included 237 diabetic kidney transplant recipients (93 on SGLT2i, 144 on DPP‑4i) followed at Hamed Al‑Essa Organ Transplant Center in Kuwait. Patients were followed prospectively for 60 months with clinical evaluations every 3 months during the first year and annually thereafter. Outcomes included changes in blood pressure, body weight, HbA1c, proteinuria, serum creatinine, graft failure, and urinary tract infection (UTI) episodes. Results The SGLT2i group had a significantly higher mean age (58.5±11.9 vs. 54.4±12.9 years, P = 0.016) and baseline HbA1c (7.53±2.11 vs. 5.30±3.71%, P < 0.001). Despite poorer baseline glycemic control, the SGLT2i group achieved comparable HbA1c levels by 12 months. SGLT2i was associated with sustained weight loss at 6, 12, 36, and 60 months (all P < 0.05), and a modest but significant reduction in systolic blood pressure at 3 months (136.2±17.4 vs. 131.8±15 mmHg, P = 0.043). Notably, proteinuria decreased significantly in the SGLT2i group at 12 months (65.5±96.2 vs. 40±68.5 mg/day, P = 0.024) and 24 months (101.7±114 vs. 67.8±93.3 mg/day, P = 0.017). Despite safety concerns, the SGLT2i group experienced significantly fewer recurrent UTI episodes during the study period (11±11.8 vs. 12±8.3 episodes, P = 0.043). Serum creatinine remained stable throughout follow‑up, and graft failure rates were comparable between groups (2.2% vs. 2.8%, P = 0.63). No major cardiovascular events were reported in either group. Conclusions In diabetic kidney transplant recipients, SGLT2 inhibitors demonstrated superior metabolic and renal benefits compared with DPP‑4i, including sustained weight loss, significant proteinuria reduction, stable graft function, and a lower incidence of recurrent UTIs. These findings support the safety and efficacy of SGLT2i in this high‑risk population and challenge traditional concerns regarding UTI risk. Larger randomized controlled trials are warranted to confirm these observations.

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The Arab Journal of Nephrology and Transplantation is the peer-reviewed open-access journal of ASNRT, published since 2008.

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