Early safety observations of peri-transplant SGLT2 inhibitor use in lung transplant recipients

Introduction

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce renal glucose and sodium reabsorption and were initially approved for the treatment of type 2 diabetes mellitus (T2DM). Early trials demonstrated improvements in glycemic control, weight, and blood pressure, and subsequent randomized studies established cardio-renal benefits, including reductions in heart failure hospitalization and slowing of chronic kidney disease (CKD) progression (1-6).

Rationale and knowledge gap

Solid organ transplant (SOT) recipients face a high burden of post-transplant metabolic and renal complications driven by pre-existing risk factors and immunosuppressive therapy. However, transplant recipients were generally excluded from major SGLT2i trials due to concerns about genitourinary infections, volume depletion/hypotension, reduced kidney function, and potential drug-drug interactions in immunosuppressed patients (2,7). In 2015, the U.S. Food and Drug Administration added warnings regarding diabetic ketoacidosis (DKA) and serious urinary tract infections, further reinforcing uncertainty in vulnerable populations (8).

Objective

Despite these concerns, emerging transplant-focused evidence suggests that SGLT2i may be feasible in carefully selected SOT recipients, with generally low rates of severe adverse events in published cohorts, including kidney, heart, liver, and mixed SOT populations (9-14). In lung transplantation (LTx), early single-center data have also begun to describe the clinical use of glucagon-like peptide-1 receptor agonists in selected recipients, further supporting growing interest in post-transplant metabolic therapy in this population (15). In contrast, data specific to LTx remain limited, and the safety of SGLT2i in the early peri-transplant period and their association with long-term outcomes such as chronic lung allograft dysfunction (CLAD) are not well defined (16). Accordingly, we evaluated early complications and long-term outcomes associated with SGLT2i exposure before transplantation or within the first 90 days after LTx in a single-center cohort, hypothesizing that SGLT2i therapy would not be associated with worse short- or long-term post-transplant outcomes. SGLT2i have demonstrated renal protective effects, including reductions in glomerular pressure and slower progression of CKD. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0642/rc).

Methods

Study design and population

This was a retrospective cohort study of all eligible adult lung transplant recipients (≥18 years) who underwent LTx at a single tertiary care center between January 2018 and May 2024. Clinical data were obtained from the electronic medical record and the institutional lung transplant database at Northwestern Memorial Hospital (Chicago, IL, USA). Potential SGLT2i-related adverse events, including genitourinary infections, were assessed by retrospective review of the electronic medical record, including clinician documentation, microbiology results, and urine studies. Multi-organ transplants and redo lung transplant procedures were excluded; only primary isolated lung transplants were included in the analytic cohort. The study protocol was approved by the Institutional Review Board of Northwestern University (Nos. STU00207250 and STU00213616). The requirement for informed consent for data collection and analysis was waived because of the retrospective nature of the study. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. All transplants were performed according to institutional protocols, United States regulations, and the principles of the Declaration of Istanbul on Organ Trafficking and Transplant Tourism; no organs were procured from prisoners or other unethical sources. Peri-operative and post-operative management at our center has been described previously (17-23). Additional details of the study methods are provided in Appendix 1.

SGLT2i exposure and SGLT2-related complications

Use of SGLT2i was ascertained from medication reconciliation records, pharmacy data, and treating physician documentation. For this study, peri-transplant SGLT2i exposure was defined as either (I) ongoing SGLT2i therapy at the time of LTx (pre-LTx use) or (II) de novo initiation of an SGLT2i within the first 90 days after transplantation (de novo post-LTx initiation). Pre-LTx SGLT2i use was defined as active treatment with any SGLT2i at the time of transplantation; for these patients, the interval from SGLT2i initiation to transplantation was recorded in months. De novo post-LTx initiation was defined as new initiation of any SGLT2i after transplantation in a recipient not receiving SGLT2i therapy at the time of LTx; for these patients, the interval from transplantation to SGLT2i initiation was recorded in days. For long-term outcome analyses, recipients who survived to postoperative day 90 were classified into three groups: pre-LTx SGLT2 users, de novo post-LTx initiators within 90 days, and recipients without SGLT2i use within 90 days. At Northwestern University Feinberg School of Medicine, SGLT2i are generally discontinued once LTx is planned or donor acceptance occurs, given the urgent nature of transplantation and the risk of euglycemic DKA. In the early postoperative period, these agents are generally not resumed until the patient is clinically stable and oral intake has been re-established.

The specific SGLT2i used (e.g., empagliflozin, canagliflozin, dapagliflozin) and the primary indication for therapy were abstracted from the prescribing documentation. Potential SGLT2-related complications were defined a priori as DKA, acute kidney injury (AKI), volume depletion or hypotension, or other adverse events that the treating team considered at least possibly attributable to SGLT2i therapy. For patients who received SGLT2i after LTx, discontinuation of therapy and the reason for discontinuation were recorded, and time from LTx to SGLT2i discontinuation (months) was calculated among those who stopped treatment.

Outcomes

Outcomes were defined a priori. Early postoperative outcomes included primary graft dysfunction (PGD) grade 3 at 72 hours [graded per International Society for Heart and Lung Transplantation (ISHLT) criteria] (24), postoperative extracorporeal membrane oxygenation (ECMO) use, thromboembolic events, and renal outcomes during the index hospitalization. Long-term outcomes included CLAD (defined per ISHLT consensus criteria) (25) and overall survival. Potential SGLT2i-related adverse events included DKA, volume depletion/hypotension, AKI, and genitourinary infections, as documented by the treating team.

Statistical analysis

Continuous variables were compared using the Mann-Whitney U test and categorical variables using Fisher’s exact test. To mitigate immortal-time bias, time-to-event analyses used a postoperative day-90 landmark; follow-up for CLAD and survival began at day 90 among patients alive and CLAD-free at that time. Kaplan-Meier methods and log-rank tests were used for unadjusted comparisons, and Cox proportional hazards models were used for adjusted analyses with prespecified covariates. Logistic regression was used for PGD grade 3. Two-sided P<0.05 was considered statistically significant.

Results

Clinical characteristics of SGLT2i-treated recipients

A total of 461 lung transplant recipients were screened, and 443 patients met the inclusion criteria for analysis (Figure 1). Among 443 lung transplant recipients in this cohort, 11 (2.5%) were treated with SGLT2i either before transplantation or within 90 days after LTx (Table 1). The median age of these patients was 64 years (range, 41–73 years), and 5 were male. The median body mass index (BMI) was 27.1 kg/m² (range, 22.0–33.9 kg/m²), with a median body surface area of 1.9 m² (range, 1.6–2.6 m²). Most patients had a history of smoking (9/11) and hypertension (10/11). Diabetes mellitus was present in 6 patients, and 3 patients had pre-existing CKD, although none required dialysis preoperatively. Median glycated hemoglobin (HbA1c) is 5.9% (range, 5.6–6.9%), and the median pre-transplant serum creatinine was 0.9 mg/dL (range, 0.6–1.5 mg/dL).

Figure 1 Flow diagram of cohort selection and classification according to SGLT2i exposure. From January 2018 to August 2024, 461 lung transplant recipients were screened. After excluding multi-organ transplants (n=9) and redo lung transplants (n=9), 443 recipients who underwent isolated primary LTx comprised the final cohort for short-term outcome analyses and were stratified according to pre-transplant SGLT2i use (pre-LTx SGLT2 use, n=7; no pre-LTx SGLT2 use, n=436). For long-term outcome analyses, 15 recipients who died within 90 days after transplantation were excluded, leaving 428 postoperative day-90 survivors. These patients were classified into three exposure groups: pre-LTx SGLT2 users (n=7), de novo post-LTx initiators within 90 days after transplantation (n=4), and recipients without SGLT2i use within 90 days after transplantation (n=417). LTx, lung transplantation; SGLT2, sodium-glucose cotransporter-2; SGLT2i, sodium-glucose cotransporter-2 inhibitors.

SGLT2i were prescribed primarily for diabetes mellitus (6/11 patients) or congestive heart failure (5/11 patients, including 1 with concomitant CKD). Empagliflozin was the most frequently used agent (8 patients), followed by dapagliflozin (2 patients) and canagliflozin (1 patient). Seven patients were already receiving an SGLT2i before LTx and continued therapy early after transplantation, whereas 4 patients initiated SGLT2i treatment de novo within 90 days after transplantation.

Underlying etiologies were interstitial lung disease (ILD) in 6 patients, chronic obstructive pulmonary disease (COPD) in 4, and pulmonary arterial hypertension in 1 patient. Single and bilateral LTx were performed in 6 and 5 patients, respectively. The median operative time was 4.2 hours (range, 1.8–6.4 hours). Intraoperative transfusion requirements were modest [median 0 units of packed red blood cells (pRBCs)], with only 1 patient receiving fresh frozen plasma (FFP) and 1 patient receiving platelets. Veno-arterial ECMO (VA-ECMO) was used intraoperatively in 3 patients.

Baseline characteristics of the study cohort

A total of 443 patients underwent LTx during the study period (Table 2). The median age at transplantation was 63.0 years [interquartile range (IQR), 54.0–68.0 years], and 249 patients (56.2%) were male. Only 7 patients (1.6%) were receiving SGLT2i at the time of transplantation. Baseline characteristics were generally similar between patients with and without pre-LTx SGLT2 use, although COPD was more frequent among pre-LTx users (57.1% vs. 19.0%, P=0.03). Among the 428 patients included in the long-term outcome cohort, 7 were pre-LTx SGLT2 users, 4 initiated SGLT2i de novo within 90 days after transplantation, and 417 had no SGLT2 exposure within 90 days. In this three-group descriptive comparison, de novo initiators more often had diabetes mellitus, higher pre-transplant creatinine levels, shorter operative times, and less frequent intraoperative VA-ECMO use than non-users. All 4 de novo initiators had ILD as the underlying diagnosis.

Postoperative complications and SGLT2i treatment course in SGLT2i-treated recipients

Patient-level postoperative courses of the 11 recipients who received SGLT2i either before or within 90 days after LTx are summarized in Table 3. Among them, 7 patients were already receiving SGLT2i at the time of transplantation. In these 7 pre-LTx SGLT2i users, no cerebrovascular accident, bowel ischemia, digital ischemia, or deep vein thrombosis occurred. Five patients developed AKI, however dialysis during the index hospitalization was not required. PGD grade 3 at 72 hours was observed in only 1 of the 7 patients. SGLT2i-related events and long-term outcomes were evaluated in all 11 SGLT2i-treated recipients (Table 3). SGLT2i therapy was continued without interruption in 10 patients, whereas 1 patient developed DKA 27 months after transplantation.

The only DKA event occurred in a 66-year-old man with COPD status post right single- LTx, who developed euglycemic DKA approximately 27 months after transplantation during admission for coronavirus disease 2019 (COVID-19) pneumonia with acute hypoxemic respiratory failure. He had been receiving empagliflozin
10 mg, and the treating team attributed the event to SGLT2i use in the setting of critical illness, dehydration, and AKI. Initial evaluation showed venous pH 7.09, partial pressure of carbon dioxide (pCO₂) 48 mmHg, venous bicarbonate 15 mmol/L, serum CO₂ 14 mmol/L, anion gap 19, beta-hydroxybutyrate 3.00, normal lactate, and glucose 180 mg/dL, consistent with euglycemic DKA. Regarding immunosuppression, his home prednisone dose was 5 mg daily, which was held while he received dexamethasone 6 mg daily for COVID-19; mycophenolate was temporarily held because of infection, and tacrolimus was initially held in the setting of AKI and supratherapeutic levels. He was treated with an insulin protocol and subsequently transitioned from insulin infusion to subcutaneous insulin; beta-hydroxybutyrate decreased to 0.15, and the DKA was documented as resolved during hospitalization. Empagliflozin was discontinued indefinitely, and he was discharged on basal and correctional/prandial insulin with endocrinology follow-up.

During follow-up (range, 331–1,112 days), CLAD with a bronchiolitis obliterans syndrome (BOS) phenotype occurred in 1 patient, and 2 patients died; the remaining 9 patients were alive at last follow-up.

Comparison of postoperative outcomes according to pre-transplant SGLT2i use in the entire cohort

Postoperative complications and early clinical course were compared between patients with and without pre-transplant SGLT2i use among all 443 lung transplant recipients (Tables 4,5). Overall rates of cerebrovascular accident, bowel or digital ischemia, pulmonary embolism, postoperative ECMO use, PGD grade 3, and durations of intensive care unit (ICU) stay, mechanical ventilation, and hospital stay were similar between groups, with no statistically significant differences. Deep vein thrombosis tended to be less frequent in patients receiving pre-LTx SGLT2i (14.3% vs. 52.5%, P=0.06), although the small number of SGLT2i-treated patients limited the power to detect meaningful differences. Overall, pre-transplant SGLT2i use was not clearly associated with an increased risk of early postoperative complications.

Predictors of PGD grade 3

Univariate logistic regression identified several perioperative factors associated with PGD grade 3 (Table S1). Among pre-operative characteristics, older age [odds ratio (OR) =0.98 per year; 95% confidence interval (CI): 0.96–1.00; P=0.02], pre-transplant dialysis (OR =6.48; 95% CI: 2.61–15.82; P<0.001), and the presence of an ECMO bridge (OR =6.46; 95% CI: 3.27–12.7; P<0.001) were significantly associated with PGD grade 3. Higher baseline creatinine (OR =2.35 per mg/dL; 95% CI: 1.11–5.77; P=0.04), lower hemoglobin (OR =0.87 per g/dL; 95% CI: 0.78–0.98; P=0.02), and longer partial thromboplastin time (PTT) (OR =1.02 per second; 95% CI: 1.00–1.04; P=0.03) were also associated with increased risk. Regarding intra-operative factors, longer operative time (OR =1.25 per hour; 95% CI: 1.09–1.43; P=0.001), larger volumes of intra-operative pRBC (OR =1.15 per unit; 95% CI: 1.09–1.22; P<0.001), FFP (OR =1.22 per unit; 95% CI: 1.11–1.35; P<0.001), and platelet transfusion (OR =1.48 per unit; 95% CI: 1.24–1.80; P<0.001), as well as VA-ECMO use (OR =2.04; 95% CI: 1.12–3.91; P=0.02), were significantly associated with PGD grade 3 on univariate analysis. Pre-transplant SGLT2i use was not significantly associated with PGD grade 3 (OR =1.11; 95% CI: 0.06–6.65; P=0.93). In the multivariable model including age, ECMO bridge, pre-LTx SGLT2 use, baseline creatinine, and intra-operative pRBC units, higher creatinine (OR =4.40; 95% CI: 1.54–12.61, P=0.006) and larger pRBC transfusion volume (OR =1.15 per unit; 95% CI: 1.08–1.23; P<0.001) remained independently associated with PGD grade 3, whereas pre-LTx SGLT2 use was not (OR =1.22; 95% CI: 0.13–11.35, P=0.86). Because only 7 recipients were exposed to SGLT2i at the time of transplantation, estimates for the exposure effect were imprecise. Based on the observed PGD grade 3 rate in the unexposed group, the study had 80% power only to detect a very large increase in risk (minimum detectable OR =10.7). Thus, moderate harmful or protective effects could not be excluded.

Association between SGLT2i use and CLAD

Among the 428 patients who were alive and free of CLAD at postoperative day 90, 7 were pre-LTx SGLT2 users, 4 initiated SGLT2i de novo within 90 days after transplantation, and 417 had no SGLT2 use within 90 days. In 5-year postoperative day-90 landmark analyses, CLAD-free survival was described across these three groups. The Kaplan-Meier curves showed no statistically significant difference, but estimates were imprecise because of the small number of exposed patients (log-rank P=0.17; Figure S1). In univariable Cox regression (Table S2), none of the pre-operative characteristics were significantly associated with CLAD, although older age showed a trend toward a lower risk [hazard ratio (HR) =0.98 per year; 95% CI: 0.97–1.00; P=0.06]. Among postoperative variables, SGLT2i use within 90 days after transplantation was not associated with CLAD (HR =0.98; 95% CI: 0.13–7.09; P=0.98). In the multivariable Cox model including age, BMI, etiology (ILD vs. others), ECMO bridge, bilateral LTx, PGD grade 3, AKI, and SGLT2 use within 90 days, SGLT2 therapy remained unassociated with CLAD (HR =1.27; 95% CI: 0.17–9.42; P=0.81).

Overall survival according to SGLT2i use

Among the 428 patients who survived to postoperative day 90 and had information on SGLT2 exposure, 7 were pre-LTx SGLT2 users, 4 initiated SGLT2i de novo within 90 days after transplantation, and 417 had no SGLT2 use within 90 days. In 5-year postoperative day-90 landmark analyses, overall survival was described across these three groups. Although the Kaplan-Meier curves showed some numerical separation, estimates were imprecise because of the very small number of exposed patients, particularly de novo initiators (log-rank P=0.10; Figure 2). In univariate Cox regression, several pre- and post-transplant factors were associated with worse overall survival, including CKD, pre-transplant dialysis, higher baseline creatinine, and multiple severe postoperative complications such as cerebrovascular accident, bowel or digital ischemia, deep vein thrombosis, pulmonary embolism, postoperative ECMO use, AKI, dialysis during the index hospitalization, hemodialysis after discharge, PGD grade 3, and longer ICU stay, ventilator duration, and hospital stay (Table S3). In the multivariable model including age, sex, BMI, CKD, etiology (ILD vs. others and COPD vs. others), ECMO bridge, bilateral vs. single LTx, and SGLT2 use within 90 days, CKD (HR =1.72; 95% CI: 1.01–2.91; P=0.04) and COPD etiology (HR =1.88; 95% CI: 1.07–3.32; P=0.03) remained independently associated with higher mortality, whereas bilateral LTx was associated with lower mortality (HR =0.55; 95% CI: 0.34–0.90; P=0.02). SGLT2i use within 90 days of transplantation was not independently associated with overall survival, but CIs were wide and included clinically important harm and benefit (HR =0.61; 95% CI: 0.15–2.51; P=0.49). In the postoperative day-90 landmark cohort, only 11 of 428 recipients (2.6%) were exposed to SGLT2i. With this exposure prevalence and the observed event counts, the study had 80% power only to detect very large HRs (minimum detectable HR =8.84 for CLAD and 5.29 for overall survival). Therefore, these time-to-event analyses should be interpreted as descriptive and hypothesis-generating.

Figure 2 Kaplan-Meier curves for overall survival stratified by SGLT2i use within 90 days after LTx. Five-year postoperative day-90 landmark Kaplan-Meier curves for overall survival stratified by SGLT2i exposure pattern. Patients were classified into three groups: no SGLT2i use within 90 days after transplantation, pre-LTx SGLT2 use, and de novo post-LTx initiation within 90 days. Follow-up was administratively censored at 5 years. Shaded areas indicate 95% CIs, and the table below shows the number of patients at risk at each time point. Because of the very small number of exposed patients, CIs are wide and the apparent overlap or separation of curves should not be interpreted as evidence of equivalence. The P value was calculated using the log-rank test. CI, confidence interval; LTx, lung transplantation; SGLT2, sodium-glucose cotransporter-2; SGLT2i, sodium-glucose cotransporter-2 inhibitors.

Sensitivity analysis

To further explore potential treatment-selection bias, we performed a descriptive sensitivity analysis restricted to recipients who did not require intraoperative VA-ECMO. In this subset, 5-year postoperative day-90 landmark analyses showed no statistically significant difference in overall survival or CLAD-free survival across the three exposure groups (log-rank P=0.10 and P=0.17, respectively; Figures S2,S3). However, these estimates remained imprecise because of the very small number of exposed patients, and no exposed patients remained at risk at 5 years. Accordingly, 5-year estimates were stably estimable only for the no-SGLT2 group, in whom 5-year overall survival was 50.1% (95% CI: 39.0–64.3%) and 5-year CLAD-free survival was 69.8% (95% CI: 58.7–83.0%).

Discussion

Key findings

In this single-center retrospective cohort of lung transplant recipients, exposure to SGLT2i before transplant or within the first 90 days after transplantation was uncommon, and no clear excess of adverse early or long-term outcomes was observed among the small number of exposed recipients. However, these descriptive observations should not be interpreted as evidence of comparative safety, and clinically meaningful harm or benefit cannot be excluded given the very small number of exposed patients and sparse events. Taken together, these findings provide an initial, reassuring safety and feasibility signal for SGLT2i use in carefully selected lung transplant recipients, although interpretation is limited by the small sample size and should be viewed as hypothesis-generating.

Strengths and limitations

Cardiovascular safety is a major consideration when introducing SGLT2i in the peri-transplant period, given the hemodynamic instability and high burden of cardiopulmonary disease in lung transplant recipients. In contemporary lung-transplant cohorts, post-transplant myocardial infarction and cardiovascular death are uncommon but not rare, and among recipients without pre-existing cardiovascular disease, major adverse cardiac events have been reported in 4.7% over >54 months of follow-up (26). In the present cohort, no myocardial infarctions or cardiovascular deaths were observed among SGLT2i-exposed patients during follow-up. Two deaths occurred in the SGLT2i group, both attributable to pneumonia rather than cardiovascular causes. While the small sample size and low event rates preclude robust comparative analyses of cardiovascular versus non-cardiovascular mortality, the absence of an observed signal for excess cardiovascular death is reassuring and aligns with safety data reported in other SOT populations. Consistent with this, prior transplant-specific data—most robustly in kidney transplantation, including randomized evidence for empagliflozin in post-transplant diabetes mellitus—have suggested acceptable short-term tolerability of SGLT2i under careful monitoring (10). Observational reports in heart and liver transplantation, as well as mixed solid-organ transplant programs, similarly describe feasible use without a dominant signal for severe adverse events, although these studies are limited by selection bias and heterogeneity (11,13,14). In contrast, lung transplant–specific evidence remains sparse. More broadly, recent lung transplant literature has highlighted the clinical importance of metabolic risk, including reports that preexisting or perioperative diabetes mellitus may be associated with worse long-term outcomes after transplantation (27). A previous retrospective cohort suggested that SGLT2i use is feasible and generally well tolerated in lung transplant recipients, providing preliminary support for the reassuring safety signal observed in our cohort and underscoring the need for larger, multicenter studies (16). Extending this prior work, our study specifically examines peri-transplant exposure (pre-transplant or within 90 days post-transplant) and evaluates lung allograft alongside mortality, addressing an important evidence gap in this highest-risk clinical window. This study has several important limitations, including its single-center retrospective design, small number of SGLT2i-exposed patients, heterogeneity in timing and indication for SGLT2i use, and potential for residual confounding and exposure misclassification. The study was not powered to detect modest differences in infrequent outcomes such as cardiovascular death, DKA, or specific infectious complications. Another important limitation is potential confounding by underlying disease etiology. COPD was overrepresented among pre-LTx SGLT2 users, possibly reflecting the clinical indication for therapy, including cardiometabolic comorbidity such as heart failure. Because COPD recipients may differ systematically from recipients with ILD or PAH in baseline cardiovascular risk, frailty, and post-transplant trajectory, the apparent descriptive safety signal may have been confounded by underlying etiology in addition to treatment selection. Accordingly, these findings should be interpreted as descriptive and hypothesis-generating (9).

Comparison with similar research

DKA is a recognized but uncommon adverse event associated with SGLT2i therapy. In our cohort, one recipient developed DKA 27 months after transplantation, which was judged possibly related to SGLT2i exposure and led to permanent discontinuation. In non-transplant populations, the absolute rate of SGLT2i-associated DKA is low—reported at approximately 0.6–2.2 per 1,000 person-years in randomized trials and 0.6–4.9 per 1,000 person-years in observational studies—with large cardiovascular outcomes data similarly showing infrequent events (0.3% with dapagliflozin vs. 0.1% with placebo) (28,29). Although the absolute risk appears low, SGLT2i-associated DKA can be life-threatening if missed, underscoring the need for vigilant clinical monitoring and prompt evaluation of compatible symptoms, with temporary drug interruption during acute illness, reduced oral intake, or peri-procedural periods.

Explanations of findings

Concerns regarding genitourinary infections represent a common barrier to SGLT2i use in immunosuppressed patients; however, available kidney-transplant data suggest that these events are generally infrequent under careful patient selection and monitoring [pooled kidney-transplant studies report urinary tract infection in 14/132 (10.6%) and genital mycosis in 1/72 (1.4%), and a large multicenter cohort reported UTIs in 6.6% and genital mycosis in 0.6%] (30,31). In a small prospective pilot study of empagliflozin in kidney transplant recipients with PTDM, bacterial UTIs occurred in 5/14 participants (vs. 9/24 matched reference patients), balanitis occurred in 1 participant (32). No genitourinary infections were identified among the SGLT2i-exposed recipients during follow-up. However, given the very small number of exposed patients, this absence of observed events should not be interpreted as evidence of low true infection risk. These findings should therefore be viewed as descriptive only.

Implications and actions needed

Future multicenter studies with larger sample sizes and standardized definitions of exposure, perioperative management, and adverse events are needed to better characterize the safety profile of SGLT2i in lung transplant recipients. Prospective studies may also help clarify whether the cardio-renal benefits observed in non-transplant populations translate meaningfully to this high-risk group.

Conclusions

In this single-center cohort, peri-transplant SGLT2i exposure was uncommon, and no clear excess of adverse outcomes was observed among the small number of exposed recipients. These descriptive observations are compatible with feasibility in carefully selected lung transplant recipients but cannot exclude clinically meaningful harm or benefit. Larger multicenter studies are needed to better define safety and clinical utility in this population.

Acknowledgments

We thank Elena Susan for English proofreading.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0642/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0642/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0642/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-0642/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of Northwestern University (Nos. STU00207250 and STU00213616), and the requirement for informed consent was waived because of the retrospective nature of the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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