Data Sources and Search Strategies

Between December 2025 and January 2026, relevant studies based on SGLT2 inhibitors and heart transplantation were searched. Data sources included Medical Literature Analysis and Retrieval System Online [MEDLINE] (with its subset PubMed), Web of Science, Cochrane database, Google Scholar, Excerpta Medica dataBASE (EMBASE), and ClinicalTrials.gov.

Reference lists of selective previously published studies were also searched for relevant papers.

The following search terms and phrases were used during this search process:

‘SGLT2 inhibitors and heart transplant’; ‘SGLT2 inhibitors and organ transplant’; ‘SGLT2 inhibitors and diabetes mellitus and heart transplant’; ‘SGLT2 inhibitors and heart transplant and clinical outcomes’.

Criteria For Inclusion and Exclusion

The criteria for inclusion were:

(a)

Studies that were based on participants with DM following heart transplantation and who were taking SGLT2 inhibitors;

(b)

Studies that reported clinical outcomes;

(c)

Studies that were published in English.

Criteria for exclusion were:

(a)

Systematic reviews, meta-analyses, mini-reviews, and literature reviews;

(b)

Repeated studies or studies that involved the same trial.

Outcomes, Definitions, and Follow-up

The clinical outcomes that were reported in the original studies are listed in Table 1.

Table 1 Clinical outcomes reported in the original studies

The primary clinical outcomes that were assessed included:

(a)

Mortality risk

(b)

Sepsis following heart transplantation

(c)

Rejection following heart transplantation

The secondary clinical outcomes that were assessed included:

(a)

Change in body weight: the body weight (in kilograms) at follow-up versus at baseline;

(b)

Change in body mass index (BMI): the BMI at follow-up versus at baseline;

(c)

Changes in serum creatinine levels: the creatinine level at follow-up versus at baseline;

(d)

Changes in HbA1c levels: change in glycated hemoglobin, at follow-up time period versus at baseline, to know if there has been any improvement in HbA1c.

(e)

Changes in glomerular filtrate rate (eGFR): Changes in eGFR signified kidney damage, more appropriately, diabetic nephropathy.

The average follow-up time period ranged from 7 to 210 months, as shown in Table 1.

Data Extraction and Quality Assessment

The authors independently extracted the following data: names of authors, publication date, types of study, types of surgery, clinical outcomes reported in each original study, the follow-up time period reported in each original study, number of participants who were assigned to an SGLT2 group and number of participants who were assigned to a control group, the baseline features of the participants, the number of events at baseline versus at follow-up, and number of events in the SGLT2 versus the control groups.

All the studies included in this analysis were observational. Therefore, the quality assessment of the studies was conducted using the Newcastle–Ottawa Scale (NOS) [7].

Statistical Analysis

The statistical analysis was carried out by the RevMan software version 5.4. This is a meta-analysis where heterogeneity is common. Heterogeneity was assessed by the Q statistic test and the I2 statistic test. When the Q statistic test was considered, a P value less or equal to 0.05 was considered statistically significant whereas a P value greater than 0.05 was considered insignificant. Assessment through the I2 statistic test was based on an increasing I2 value, implying an increasing heterogeneity. A random-effects statistical model was used during subgroup analysis.

In addition, for dichotomous data, risk ratios (RR) with 95% confidence intervals (CI) were used to present the results of the analysis. However, for continuous data with the mean and standard deviation provided, the weighted mean difference (WMD) with 95% CI was used to summarize the data post hoc.

A sensitivity analysis was also conducted to verify consistency across the studies. This sensitivity analysis was conducted using an exclusion method. Each study involved in the assessment of an endpoint was excluded one at a time, and a new analysis was carried out each time to observe for any deviation or significant difference from the main results. For example, if studies A, B, and C were involved in assessing graft rejection, the main result would include all three studies. However, when sensitivity analysis was carried out, study A was excluded, and a new analysis was carried out using studies B and C. Then another analysis was carried out using studies A and C, and A and B, respectively, and the results were compared with the main results for any significant differences. This meta-analysis consisted of fewer than ten studies; therefore, publication bias was visually observed through funnel plots that were generated through the RevMan software.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Therefore, ethical approval was not required.