In this real-world cohort of solid organ transplant recipients with diabetes treated with SGLT2 inhibitors, we describe a modest and temporally delayed improvement in glycemic control, a sustained and clinically meaningful reduction in body weight, and a decline in renal function among few participants observed after the first year of therapy. Overall, we recorded a relatively low incidence of genitourinary infections. The discontinuation rate was comparable to that reported in large cardiovascular outcome trials in the T2D population. However, there were some cases of severe infection that may warrant caution with regards to the widespread implementation of therapy with SGLT2 inhibitors for PTDM.

Unlike the early HbA1c reductions consistently described in major randomized trials for T2D [9, 10, 17], the maximal HbA1c reduction in our cohort occurred between years 2 and 3. Significant changes occurred during time in the concomitant use of other diabetes drugs, including GLP-1RA, which could contribute to declining HbA1c levels. This pattern may reflect the unique metabolic environment of transplant recipients, characterized by fluctuating immunosuppressive exposure, variable insulin resistance, heterogeneous β-cell reserve, and dynamic changes in the glucose-lowering regimen. Baseline glycemic control in our population was relatively close to target, which may have limited the early effect. From a clinical standpoint, these findings suggest that in PTDM, SGLT2 inhibitors may contribute to metabolic stabilization and treatment expectations should be framed accordingly.

Weight reduction was progressive and sustained over time, reaching magnitudes comparable to those described in both transplant-specific cohorts and non-transplant T2DM populations. It should be noted that reduction in steroid dose or use, along with increase in exercise, may be factors that enable weight loss after transplantation. Given the high prevalence of overweight, metabolic syndrome, and cardiovascular risk factors in transplant recipients, weight loss may represent one of the most clinically relevant benefits of SGLT2 inhibitors in this setting. Even in the absence of dramatic glycemic changes, weight reduction may contribute to improved blood pressure control, reduced insulin requirements, and long-term cardiovascular risk mitigation.

A challenging finding concerns renal function. While SGLT2 inhibitors have robust renoprotective effects in chronic kidney disease and T2DM populations [8, 18, 19], a few patients with long-term observation in our cohort exhibited a progressive decline in eGFR beyond the first year of therapy. Importantly, the decline did not appear to reflect the early hemodynamic dip typically observed after SGLT2 initiation. In transplant recipients, chronic exposure to calcineurin inhibitors, pre-existing structural kidney damage, hypertension, and long-standing diabetes may create a renal milieu that differs substantially from that of participants in randomized trials. Reassuringly, the incidence of ≥ 50% eGFR decline was 4.2% over 1.6 years, similar to rate observed in the dapagliflozin arm of the DAPA-CKD trial (2.6%/year) and nominally lower to that observed in the placebo arm (4.8%/year) [8]. Although the signal is due to a small number of cases, it underscores the need for cautious renal monitoring and individualized risk–benefit assessment when prescribing SGLT2 inhibitors in PTDM, particularly beyond the first year of therapy. In the absence of a control group, results remain descriptive and it is not possible to determine whether the observed decline represents drug-related harm or the natural progression of chronic kidney dysfunction in this high-risk population.

When compared with the existing literature on SGLT2 inhibitors in PTDM, our findings show some consistencies and substantial divergence. In our cohort compared, the magnitude of HbA1c reduction and weight loss was broadly comparable, and infection rates were slightly lower, although severe cases (urosepsis) were proportionally more represented. The main difference lies in the longer follow-up and the observation of a significant renal decline beyond 2 years, an outcome not captured in previous studies. Therefore, our data do not contradict existing evidence but rather extend it temporally, highlighting the importance of long-term assessment in this population. However, a minority of patients were observed beyond 24 months contributing to the observed decline in eGFR, implying that more data will be needed.

This study has notable strengths. First, the observation time extended beyond the typical 6–12 months follow-up of most prior studies on SGLT2 inhibitor therapy in PTDM. Second, we included multiple organ types rather than kidney transplant recipients alone.

At the same time, important limitations must be acknowledged. The retrospective design and single-center setting limit generalizability. The sample size restricts statistical power and precludes robust subgroup analyses (such as by sex). The absence of a control group makes the study descriptive and prevents causal inference, particularly regarding renal outcomes. Furthermore, baseline renal trajectories prior to SGLT2 initiation were not available, making it impossible to determine whether the observed decline represents acceleration, stabilization, or natural progression. Also, the change in HbA1c and body weight over time should not be entirely attributed to SGLT2 inhibitors, as other therapies changed during the observation, including GLP-1RA and insulin. Therefore, the present results have to be viewed mainly as descriptive, with limited possibility of evaluating the true efficacy of SGLT2 inhibitors in this population.

Future research should prioritize prospective, multicenter studies specifically designed for transplant populations, ideally including matched control groups and predefined renal and cardiovascular composite endpoints analogous to those used in major SGLT2 trials. Long-term follow-up beyond 2 years is essential to clarify whether the renal signal we observe in this study reflects transplant-specific vulnerability or statistical fluctuation. From a clinical perspective, future work should also aim to identify subgroups of transplant recipients who derive the greatest metabolic and cardiovascular benefit with minimal renal risk, enabling more personalized therapeutic strategies.