The Efficacy and Safety of SGLT2 Inhibitors in Diabetes Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

Kanachai Boonpiraks; Pajaree Krisanapan; Suthiya Anumas; Charat Thongprayoon; Wisit Cheungpasitporn; Pattharawin Pattharanitima

doi:10.12688/f1000research.162502.1

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Systematic Review

The Efficacy and Safety of SGLT2 Inhibitors in Diabetes Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

[version 1; peer review: 1 approved]

Kanachai Boonpiraks¹, Pajaree Krisanapan², Suthiya Anumas ¹, Charat Thongprayoon³, Wisit Cheungpasitporn³, Pattharawin Pattharanitima ¹

Kanachai Boonpiraks¹, Pajaree Krisanapan², [...] Suthiya Anumas ¹, Charat Thongprayoon³, Wisit Cheungpasitporn³, Pattharawin Pattharanitima ¹

PUBLISHED 25 Mar 2025

Author details Author details

¹ Chulabhorn International College of Medicine, Klong Luang, Pathum Thani, 12120, Thailand
² Internal Medicine, Thammasat University, Klong Luang, Pathum Thani, 12120, Thailand
³ Department of Medicine, Mayo Clinic Minnesota, Rochester, Minnesota, 55905, USA

Kanachai Boonpiraks
Roles: Conceptualization, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Pajaree Krisanapan
Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Software, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Suthiya Anumas
Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Methodology, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Charat Thongprayoon
Roles: Conceptualization, Formal Analysis, Methodology, Supervision, Writing – Review & Editing

Wisit Cheungpasitporn
Roles: Conceptualization, Formal Analysis, Methodology, Supervision, Writing – Review & Editing

Pattharawin Pattharanitima
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Background

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have shown cardiorenal benefits in the general population; however, evidence regarding their efficacy and safety in kidney transplant recipients (KTRs) remains sparse. This meta-analysis seeks to evaluate the therapeutic efficacy and safety profile of SGLT-2 inhibitors specifically in the diabetes KTR population.

Methods

We conducted a systemic review and meta-analysis following a registered protocol in the PROSPERO (CRD42023404886). A comprehensive literature search was performed using PubMed, Cochrane, and Scopus databases up to October 23^th, 2024. We included observational and clinical trials which compared SGLT-2 inhibitors with control groups in KTRs. Risk of bias was evaluated by funnel plot. We reported differences in treatment effects as risk ratios (RRs) or weighted mean difference (WMD) with 95% confidence intervals (CIs).

Results

A total of seven studies comprising 2,713 patients were included in this analysis. SGLT-2 inhibitors were associated with a significant reduction in HbA1c levels (WMD -0.37%; 95% CI -0.73 to -0.01; p = 0.04) and BMI (WMD -0.89 kg/m²; 95% CI -1.27 to -0.50; p < 0.001). Additionally, SGLT-2 inhibitors demonstrated a beneficial effect in reducing mortality (RR 0.25; 95% CI 0.06 to 0.98; p = 0.05) and cardiovascular disease (CVD) (RR 0.41; 95% CI 0.17 to 0.98; p = 0.04). However, SGLT-2 inhibitors did not demonstrate benefit in kidney-related outcomes. Importantly, there was no significant increase in adverse events, including urinary tract infections, genital mycotic infections, urosepsis, or allograft rejection.

Conclusions

SGLT-2 inhibitors effectively reduced mortality, cardiovascular disease, HbA1c levels and BMI in KTRs without increasing the risk of infections or allograft rejection. However, they did not demonstrate a significant benefit in kidney-related outcomes.

Keywords

SGLT-2 inhibitors, diabetes mellitus, kidney transplant

Corresponding authors: Suthiya Anumas, Pattharawin Pattharanitima

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2025 Boonpiraks K et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Boonpiraks K, Krisanapan P, Anumas S et al. The Efficacy and Safety of SGLT2 Inhibitors in Diabetes Kidney Transplant Recipients: A Systematic Review and Meta-Analysis [version 1; peer review: 1 approved]. F1000Research 2025, 14:329 (https://doi.org/10.12688/f1000research.162502.1) First published: 25 Mar 2025, 14:329 (https://doi.org/10.12688/f1000research.162502.1) Latest published: 25 Mar 2025, 14:329 (https://doi.org/10.12688/f1000research.162502.1)

Introduction

Diabetes mellitus (DM) and post-transplantation DM (PTDM) is a well-recognized transplant comorbidity. Despite the distinct pathophysiological mechanisms, both conditions contribute to poorer prognosis and decreased survival rates in kidney transplantation recipients (KTRs).^1,2

A recent meta-analysis indicated a significant increase in all-cause mortality and graft failure in PTDM patients with hazard ratios (HR) of 1.67 and 1.35, respectively.³ Moreover, transplant recipients carry a significantly higher cardiovascular (CV) risks compared to the general population.^4,5 This risk is further heightened with comorbid pretransplant DM or PTDM.^6,7 For instance, a long-term study in KTRs reported that PTDM and pretransplant DM were associated with a 1.2-fold and 5.1-fold increased risk of all-cause mortality, respectively, with CV events being the leading cause of death.⁷ Therefore, in order to improve outcomes among kidney transplant patients, it is crucial to prioritize proper glycemic control and reduce CV risks.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors demonstrate substantial potential in mitigating cardiovascular risks and improving long-term renal outcomes.^8,9 The EMPA-REG OUTCOME trial first reported the CV benefits of Empagliflozin in type 2 diabetic mellitus (T2DM) patients, demonstrating a notable decrease in CV death.¹⁰ Subsequently, there has been a surge of interest in SGLT-2 inhibitors. Several meta-analyses have consistently demonstrated a reduction in the risk of major adverse cardiovascular events (MACE), including non-fatal myocardial infarction (MI), non-fatal stroke and CV deaths as well as a reduction in hospitalized heart failure.^11,12

In patients with chronic kidney disease (CKD), strong evidence from large randomized controlled trials (RCTs) has consistently shown that SGLT-2 inhibitors can significantly reduce kidney disease progression and cardiac death by 28-39%.^20–22 These reno-protective effects are particularly notable in patients, irrespective of coexisting type 2 diabetes (T2DM).⁹ Nevertheless, there remains a paucity of large-scale randomized controlled trials (RCTs) and comprehensive meta-analyses to conclusively validate the efficacy and safety profile of SGLT-2 inhibitors in KTRs. As a result, clinical guidelines for the administration of SGLT-2 inhibitors in this specific population are currently constrained.

A recent meta-analysis¹³ performed in 2020, comprising 8 studies involving a total of 132 participants, has provided evidence of the effectiveness of SGLT-2 inhibitors in treating DM among KTRs. The analysis demonstrated that SGLT-2 inhibitors effectively lower HbA1c levels, reduce body weight, and preserve kidney function, without reporting any serious adverse events. Previous research has primarily concentrated on evaluating differences between baseline and study endpoint measures, rather than employing a comparative analysis with a control group. Thus, we conducted this meta-analysis to compare the outcomes of SGLT-2 inhibitors with control groups. The aim of this study is to investigate the efficacy of SGLT-2 inhibitors in terms of renal benefits, glycemic control, metabolic profile improvement, mortality, and CVD outcome, as well as the safety profiles of SGLT-2 inhibitors among KTRs.

Methods

Search strategy and selection criteria

The meta-analysis was conducted following a registered protocol in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42023404886). A systematic literature search of PubMed, Cochrane and Scopus databases from the inception until October 23, 2024 was conducted independently by three investigators (K.B., P.K. and P.P.). The search terms, including “Kidney” AND “Transplant” AND “Sodium glucose co-transporter 2 inhibitor” were used to assess the efficacy and safety of SGLT-2 inhibitors among kidney transplant recipients. Supplement material (Supplement; Table S1) provides a comprehensive description of the search strategy employed. The search was limited to human studies, and no language restrictions were applied. Additionally, a manual search of the references of the included studies was conducted for additional relevant studies. The implementation and reporting of this meta-analysis adhered to the standards of the PRISMA Statement.¹⁴

Studies were included in this meta-analysis if they were observational (case-control or cohort) or clinical trials that evaluated cardiovascular and kidney outcomes of SGLT-2 inhibitors compared to a control group in adults aged 18 years or older who had undergone kidney transplantation. Eligible studies had to report alterations in at least one of the following outcomes: estimated glomerular filtration rate (eGFR), urine protein creatinine ratio (UPCR), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and adverse outcomes. Studies that primarily reported other outcomes or that included other glucose lowering medications without a subgroup report for SGLT-2 inhibitors alone were excluded. Retrieved studies were independently reviewed for eligibility by three investigators (K.B., S.A. and P.P.). Discrepancies were resolved through discussion among all authors.

Data extraction and quality assessment

Data collection was done independently by three investigators (K.B., S.A. and P.P). A standardized data collection form was used to collect the following variables from each included study: study title, author names, publication year, study type, the country where the study was conducted, study drugs, number of participants, age, gender, type of DM (T2DM vs PTDM), transplant duration, immunosuppressive drugs, follow-up time, eGFR, UPCR, HbA1c, BMI, SBP, DBP, and adverse events.

The quality of each study was independently assessed by each investigator (P.P. and P.K.). Randomized controlled trials (RCTs) were evaluated using the Cochrane Risk of Bias (RoB 2) tool¹⁵ (Supplement; Table S2), while non-randomized control studies were evaluated by the Risk of Bias In Non-randomized Studies – of Interventions (ROBIN-I) tool¹⁶ (Supplement; Table S3). Publication bias was examined by a funnel plot.

Statistical analysis

This meta-analysis was conducted using Review Manager (RevMan) [Computer program] Version 5.4. The Cochrane Collaboration, 2020. The differences in effects were reported as risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference (WMD) with 95% CIs for continuous outcomes. In cases where the required data was not originally provided in the articles, we procured it through direct communication with the investigators. Participants in RCTs were analyzed in intention-to-treat groups.

Heterogeneity was evaluated using χ² and/or the I² statistic, where an I² value above 50% or a p-value below 0.1 indicated significant heterogeneity. In cases of significant heterogeneity, a random-effect model was employed for the meta-analysis. Publication bias was assessed by funnel plot.¹⁷. Planned subgroup analysis for the primary outcomes stratified by the types of publication (observational studies vs. controlled trials) was not performed due to insufficient data. For all analyses, statistical significance was defined as a p-value less than 0.05.

Results

Study characteristics

Our search strategy identified a total of 611 potential articles as shown in Figure 1, with 92 duplicates identified and subsequently removed. The remaining 519 articles underwent an initial screening based on their titles and abstracts, leading to the exclusion of 351 articles due to their lack of relevance. Consequently, 168 articles underwent a full comprehensive review. 161 studies were excluded based on factors such as publication type, lack of outcomes of interest, inappropriate population of interest, ongoing trials, and full-text unavailable. As a result, a total of 7 studies were included in this meta-analysis, consisting of 5 retrospective cohort studies,^17–21 1 RCT,²² and 1 prospective interventional trial,²³ with baseline characteristics summarized as shown in Table 1.

Figure 1. PRISMA flow of search methodology and selection process.

Table 1. Characteristics of the Included Studies.

Author (Year)	Halden et al. (2019)	Schwaiger et al. (2019)	Hisadome et al. (2021)	Lim et al. (2022)	Demir et al. (2023)	Mahmoud et al. (2023)	Lim et al. (2024)
Study type	Double-blinded, randomized controlled trial	Prospective, interventional trial (with 2 phases of insulin and a switch to SGLT2i)	Retrospective cohort with IPTW analysis	Retrospective cohort with propensity score matching	Retrospective cohort	Retrospective cohort with case-matching	Retrospective cohort with propensity score matching
Country	Norway	Austria	Japan	Korea	Türkiye	Kuwait	Korea
Total participants, n	44	14^a	85	2083	57	168^f	254
SGLT2i	22	8	28	226	36	98	127
Control	22	14	57	1857	21	70	127
Study drug(s)	Empagliflozin	Empagliflozin	Various SGLT2i^b	Empagliflozin or dapagliflozin	Empagliflozin or dapagliflozin	Canagliflozin	Empagliflozin or dapagliflozin
Control(s)	Placebo	Insulin	Other oral hypoglycemic agents^c	Metformin or DDP-4 inhibitors or insulin	Other antiglycemic therapies, including insulin	Metformin, sulfonylurea, DPP4 inhibitors or insulin	Metformin, Sulfonylurea, DPP4 inhibitors or insulin
Total follow-up duration, months	6	12	12	9^e	12	12	56.3
Type of DM, n (%)
PTDM	44 (100)	14 (100)	0	475 (22.8)	31 (54.4)	75 (44.6)	43 (16.9)
T2DM	0	0	85 (100)	1608 (77.2)	26 (45.6)	93 (55.4)	211 (83.1)
Duration of DM, years	N/A	5.7 ± 4.8	N/A	N/A	14.8 ± 11.0	N/A	N/A
Male, n (%)	34 (77.3)	7 (50)	65 (76.5)	1399 (67.2)	36 (63.2)	107 (63.7)	179 (70.5)
Age, years	SGLT-2i: 63 [31, 72] Control: 59 [21,75]	56.5 ± 7.9	55.4 ± 8.7	52.4 ± 10.7	51.3 ± 11.0	SGLT-2i: 56 [N/A] Control: 57 [N/A]	SGLT-2i: 54 [46, 60] Control: 55 [47, 60]
Weight, kg	SGLT-2i: 92 [81.8, 104.5] Control: 84 [79.3, 94.0]	74.8 ± 17.2	71.0 ± 10.4	N/A	N/A	N/A	N/A
BMI, kg/m²	SGLT-2i: 28.8 [24.7, 39.3] Control: 27.5 [22.4, 45.8]	27.3 ± 5.2	25.7 ± 3.6	23.9 ± 3.6	28.5 ± 4.5	SGLT-2i: 31.4 [N/A] Control: 29.7 [N/A]	SGLT-2i: 25.3 [22.0, 27.4] Control: 25.2 [23.1, 27.7]
History of CAD, n (%)	N/A	10 (71)	43 (50.6)	253 (12.1)	27 (47.4)	N/A	33 (13.0)
Systolic BP, mmHg	SGLT-2i: 143 [111, 176] Control: 140 [100, 163]	150 ± 26	128 ± 15	N/A	N/A	N/A	N/A
Diastolic BP, mmHg	SGLT-2i: 79 [63, 94] Control: 82 [55, 94]	86 ± 14	73 ± 10	N/A	N/A	N/A	N/A
eGFR, ml/min/1.73m²	SGLT-2i: 66 [41, 83] Control: 59 [44, 82]	55.6 ± 20.3	48.5 ± 13.4	68.2 ± 19.9	72.4 ± 18.7	SGLT-2i: 67.2 [N/A] Control: 63.8 [N/A]	N/A
Creatinine, mg/dL	N/A	1.3 ± 0.4	N/A	1.2 ± 0.5	1.1 ± 0.3	N/A	N/A
UPCR (mg/g)	SGLT-2i: 100 [60, 150] Control: 90 [50, 120]	289 [190-808]	400 ± 600	N/A	SGLT-2i: 321 [45, 2565] Control: 229 [63, 909]	N/A	N/A
Fasting blood sugar (mg/dL)	SGLT-2i: 144 [90, 236] Control: 132 [81, 225]	N/A	N/A	143 ± 67	N/A	N/A	N/A
HbA1c (%)	SGLT-2i: 6.9 [6.5, 8.2] Control: 6.8 [6.1, 7.2]	6.5 ± 0.8	7.6 ± 1.2	7.3 ± 1.4	8.1 ± 1.9	SGLT-2i: 8.0 [N/A] Control: 7.2 [N/A]	SGLT-2i: 7.1 [6.3, 8.1] Control: 6.9 [6.1, 7.8]
Hemoglobin (g/dL)	SGLT-2i: 13.9 [13.1, 14.4] Control: 13.2 [12.1, 14.6]	12.7 ± 1.9	N/A	N/A	N/A	N/A	N/A
Hematocrit (%)	SGLT-2i: 43 [39, 45] Control: 43 [39, 44]	38.8 ± 5.4	N/A	N/A	N/A	N/A	N/A
Other glucose-lowering therapy, n (%)
Insulin	8 (18.2)	14 (100)	61 (71.8)	1155 (55.4)	29 (50.9)^d	102 (60.7)	N/A
Metformin	2 (4.5)	N/A	4 (4.7)^d	1224 (58.8)	N/A	136 (81)	N/A
Sulfonylurea	7 (15.9)	N/A	4 (4.7)^d	725 (34.8)	N/A	16 (9.5)	N/A
DPP4 inhibitors	N/A	N/A	42 (49.4)^d	1144 (54.9)	N/A	66 (39.3)	N/A
Time Since Transplant, years	SGLT-2i: 3 [1, 16] Control: 3 [1, 15]	5.8 ± 4.8	N/A	0.25	SGLT-2i: 5 [0, 13] Control: 1.5 [0, 9]	7.4 ± N/A	1.12 [0.2, 2.51]
Living donor, n (%)	16 (36)	N/A	N/A	1483 (71.2)	54 (94.7)	127 (75.6)	200 (78.7)
Immunosuppressive drugs, n (%)
Tacrolimus	35 (79.5)	11 (79)	83 (97.6)	1705 (81.9)	57 (100)	127 (75.6)	221 (87.0)
Cyclosporin	6 (13.6)	3 (21)	3 (3.5)	406 (19.5)	N/A	31 (18.5)	36 (14.2)
Everolimus	2 (4.5)	0	25 (29.4)	N/A	N/A	N/A	N/A
Mycophenolate	40 (90.9)	14 (100)	61 (71.8)	N/A	57 (100)	N/A	N/A
Steroid	43 (97.7)	14 (100)	85 (100)	2038 (97.9)	57 (100)	N/A	N/A
Trough level, ng/mL
Tacrolimus	SGLT-2i: 5.4 [4.6, 6.9] Control: 6.2 [5.0, 6.8]	8.4 ± 3.1	2.0 ± 1.1	6.0 ± 1.5	N/A	N/A	N/A
Cyclosporin	SGLT-2i: 94 [80, 105] Control: 100 [94, 100]	64.0 ± 11.5	N/A	N/A	N/A	N/A	N/A
Everolimus	SGLT-2i: 6.2 [6.2, 6.2] Control: 10 [10, 10]	N/A	N/A	N/A	N/A	N/A	N/A
Source of funding	South-Eastern Norway Regional Health Authority, the Norwegian Diabetes Association, and Oslo Diabetes Research Centre.	None	None	Ministry of Health & Welfare, Republic of Korea and the Korean Society of Nephrology	None	None	Ministry of Health & Welfare, Republic of Korea and the Ministry of Education

a Started with 14 patients but completed study with only 8

b Canagliflozin or Ipragliflozin or Luseogliflozin or Empagliflozin or Dapagliflozin or Tofogliflozin

c DDP-4 inhibitors or Glinides or Metformin or Sulfonylureas or Alpha-glucosidase inhibitors-1

d Exclusively in the control group

e Total follow-up time was 62.9 ± 42.2 months but the efficacy outcomes were reported after 9 months from the baseline

f Counted only patients received SGLT2i and the control group

Overall, a total of 2,713 patients were included in this systematic review, with 545 patients in the SGLT-2 inhibitors group. These agents were primarily indicated for T2DM (74%) more than PTDM (26%). Specific SGLT-2 inhibitors prescription was reported in 383 participants from 5 studies,^{17–19,22,23} empagliflozin was the most frequently administered, accounting for 48%, followed by canagliflozin (28%), dapagliflozin (20.6%), ipragliflozin (1.8%), luseogliflozin (1.3%), and tofogliflozin (0.3%). In the control group, only one RCT²² used a placebo, while the remaining studies^17–21,23 utilized other hypoglycemic agents, including insulin, metformin, dipeptidyl peptidase 4 (DPP-4) inhibitors, and sulfonylurea. Insulin was prescribed for 13.4% of 2,451 patients, whereas metformin was the most common oral hypoglycemic agent (OHA), accounting for 57% of 2,380 patients evaluated,^18–20,22 followed by DPP-4 inhibitors, which accounted for 54% of 1,252 patients evaluated.^18–20

The median total follow-up duration was 9 [9, 12] months. Most patients were male (67%) with a mean age of 53.1 ± 11.7 years and a BMI of 24.7 ± 4.3 kg/m². The baseline HbA1c was 7.3 ± 1.4, and the duration of DM was reported in only 2 studies^17,23 with a mean of 13.0 ± 10.1 years among 99 patients evaluated. Notably, only 15% of the 2,501 patients evaluated^{17–19,21,23} had a history of coronary artery disease (CAD).

In terms of baseline allograft function, the mean serum creatinine (Cr) was 1.2 ± 0.5 mg/dL among 2,154 evaluated patients,^17,19,23 and the mean eGFR was 67 ± 21 ml/min/1.73 m² among 2,451 evaluated patients. Of the 200 available patients, the mean UPCR was 293 ± 919 mg/g of Cr.^17,18,22,23 The time since transplant ranged from 3 months to 7.4 years with a median duration of 1.8 [0.3, 5.6] years. Nearly two-thirds (77%) of 2,454 reported patients received kidneys from living-donors.^17,19–22 The most predominant immunosuppressive medication was tacrolimus. Among 2,226 patients, the tacrolimus trough level was 5.9 ± 1.7 ng/mL.^18,19,22,23

Efficacy of SGLT-2 inhibitors on kidney-related outcomes

Kidney related outcomes were evaluated based on changes in eGFR and reductions in UPCR from baseline. Among 6 studies,^{17–20,22,23} the use of SGLT-2 inhibitors did not result in a significantly higher eGFR compared to the control, with a weighted median difference (WMD) of 0.69 mL/min/1.73 m² (95%CI -0.96, 2.34; p = 0.41; I² = 55%) as shown in Figure 2A. In terms of UPCR reduction, only 3 studies^17,18,22 involving 186 patients reported no statistically significant decrease in UPCR during the follow-up period (WMD = 9.42 mg/g; 95%CI -18.93, 37.76; p =0.51, I² = 0%) as shown in Figure 2B.

Figure 2. Forest plots of the efficacy of SGLT-2 inhibitors on kidney-related outcomes.

Efficacy of SGLT-2 inhibitors on metabolic profiles

Across 6 studies,^{17–20,22,23} SGLT-2 inhibitors resulted in a significant reduction in HbA1c levels by -0.37% (95% CI -0.73, -0.01; p = 0.04) compared with the control, with significant heterogeneity (I² = 93%) as shown in Figure 3A. Additionally, SGLT-2 inhibitors significantly reduced BMI from baseline compared with the control, with a WMD of -0.89 kg/m² (95% CI -1.27, -0.50, p <0.001, I² = 55%) as shown in Figure 3B.

Figure 3. Forest plots of the efficacy of SGLT-2 inhibitors on metabolic profiles.

However, regarding the effect on blood pressure, data on systolic blood pressure (SBP) were reported in only 3 studies^18,20,22 involving a total of 297 patients. The analysis revealed no significant reduction in SBP with SGLT-2 inhibitors compared to the control, with a WMD of -0.18 mmHg (95%CI -8.57, 8.21; p = 0.97), with significant heterogeneity (I² = 89%) as shown in Figure 3C.

Efficacy of SGLT-2 inhibitors on all-cause mortality and cardiovascular diseases

Among the 7 studies involving 2,168 patients, there were only 40 deaths reported, primarily in 3 studies.^17,19,21 Over a 9-month follow-up period, SGLT-2 inhibitors showed significantly reduced all-cause mortality compared to placebo, with a risk ratio (RR) of 0.25 (95%CI 0.06, 0.98; p = 0.05; I² = 33%) as shown in Figure 4A.

Figure 4. Forest plots of the efficacy of SGLT-2 inhibitors on mortality and CVD.

Regarding CV outcomes only 3 studies^18,20,21 involving 253 patients assessed the impact of SGLT-2 inhibitors on cardiovascular disease (CVD). Over a follow-up period of 9 months, SGLT-2 inhibitors showed significantly reduced CVD compared to the control, with a risk ratio (RR) of 0.41 (95%CI 0.17, 0.98; p = 0.04; I² = 0%) as shown in Figure 4B.

Adverse events of SGLT-2 inhibitors

There were no significant differences in adverse events incidence between the SGLT-2 inhibitors and the control group. In terms of infection, SGLT-2 inhibitors did not significantly increase the risk of overall urinary tract infection (UTI), compared to the control group, with a RR of 0.51 (95% CI 0.25, 1.01; p = 0.05) with a significant heterogeneity (I² = 79%) across 7 studies^17–23 as shown in Figure 5A. When specifically examining genital mycotic infections, only 4 studies with 2,438 patients reported outcomes.^17,19,21,22 SGLT-2 inhibitors also did not significantly increase the risk of genital mycotic infection compared to the control, with a RR of 0.88 (95% CI 0.19, 4.08; p = 0.87; I² = 18%) as shown in Figure 5B. Of 2 studies^20,22 involving 212 patients that evaluated the outcome of urosepsis, SGLT-2 inhibitors also did not significantly increase the risk of urosepsis, with a RR of 1.33 (95% CI 0.17, 10.58; p = 0.79; I² = 0%) as shown in Figure 5C.

Figure 5. Forest plots of the adverse events of SGLT-2 inhibitors.

Regarding other adverse events, SGLT-2 inhibitors did not significantly increase the risk of allograft rejection compared to the control, with a RR of 0.53 (95% CI 0.11, 2.44; p = 0.23; I² = 31%) across 3 studies,^17,18,22 involving 186 patients as shown in Figure 5D. There were no any diabetic ketoacidosis (DKA) cases reported among included studies.

Evaluation of publication bias

The funnel plots depicting standard error by mean differences and risk ratios were evaluated, as illustrated in Supplemental Figure S5-S7 (Refer Extended data). These assessments revealed no significant evidence of publication bias, as the plots exhibit symmetry.

Discussion

Our systematic review and meta-analysis focused on the safety and efficacy of SGLT-2 inhibitors among KTRs. Our findings indicate that SGLT-2 inhibitors significantly reduced HbA1c and BMI compared to the control, without increasing adverse events, including infection and allograft rejection. Notably, while SGLT-2 inhibitors showed no measurable impact on kidney-related outcomes, they conferred a substantial benefit by markedly reducing mortality and cardiovascular disease risk among KTRs.

In non-transplant population, a recent meta-analysis of large placebo-controlled trials demonstrated a significant 37% reduction in the kidney disease progression among T2 DM patients using SGLT-2 inhibitors.²⁴ This kidney benefit was consistent across subgroups, regardless of diabetic status, primary kidney diseases, or kidney function.²⁴ The renal benefits of SGLT-2 inhibitors can be attributed to increased urinary glucose excretion, leading to osmotic diuresis and enhanced excretion of sodium and fluid.²⁵ This helps mitigate glomerular hyperfiltration, reduce renal inflammation and fibrosis, and preserve renal function.²⁵ Based on these findings, similar renal benefits may be anticipated in the context of kidney transplant recipients (KTRs). However, the mechanism of SGLT-2 inhibitors, which promotes glucose excretion via urine, could potentially increase infection risk—an important concern in this population.

In contrast to findings in the non-transplant population, our meta-analysis revealed a neutral impact of SGLT-2 inhibitors on kidney function, as assessed by eGFR and UPCR. This finding was consistent with a previous meta-analysis by Chewcharat et al,¹³ which demonstrated no significant decline in eGFR and UPCR by the end of the study with SGLT-2 inhibitors. This neutral effect may be attributed to the comparatively shorter follow-up periods, with a median duration of 12 months. In contrast, non-transplant studies typical have 2-3 years follow-ups, during which the renal benefits of SGLT-2 inhibitors, especially in eGFR, become more pronounced compared to the placebo group after 12 months.^26–28

Given that KTRs have a significant elevated risk of CV death, 10 to 20 times higher than the general population,^5,29 SGLT-2 inhibitors have been proposed as a new hope in this group. Previous meta-analysis in non-transplant CKD patients have shown promising results for SGLT-2 inhibitors in reducing composite CV death or hospitalization for heart failure, with a remarkable 23% decrease compared to placebo. These finding were observed in patients with an average baseline eGFR of 65 mL/min/1.73 m^2.24 The recent EMPA-KIDNEY trial,²⁶ and DAPA-CKD trial,²⁷ which included CKD patients with eGFR as low as 20 and 25 mL/min/1.73 m², respectively, demonstrated a significant reduction in CV death: 16% with empagliflozin and 31% with dapagliflozin over a 2-year follow-up period. This benefit was consistent across a range of eGFR levels, though KTRs were not included in these trials. Despite the absence of large-scale studies specifically involving KTRs, our meta-analysis reveals that SGLT-2 inhibitors significantly reduce mortality and cardiovascular disease in this unique population, offering a compelling new therapeutic avenue to address their elevated cardiovascular risk.

Regarding the efficacy of SGLT-2 inhibitors on metabolic profiles, the reduction of 0.37% in HbA1c levels compared to the control group aligns with previous meta-analyses conducted by Okinomaki et al.³⁰ and Chewcharat et al.,¹³ which reported reductions of 0.45% and 0.57% in HbA1c levels from baseline, respectively. Our findings demonstrated that SGLT-2 inhibitors are also effective when compared to standard therapies, including insulin and other oral hypoglycemic agents. Given that tacrolimus can elevate blood glucose levels by inducing insulin resistance and increasing glucose absorption in the gastrointestinal tract,³¹ it should be noted that 82.5% of our patients received tacrolimus as part of their immunosuppressive regimen. Moreover, our meta-analysis showed that SGLT-2 inhibitors also benefit BMI, with a significant reduction of 0.89 kg/m² compared to the control. This is consistent with the previous 2 meta-analyses conducted in non-diabetic adults with overweight, which reported a reduction of 0.47 kg/m² compared to placebo.^32,33

Within current clinical practice, concerns persist regarding the potential adverse events associated with SGLT-2 inhibitors, particularly UTIs¹³ and DKA,³⁴ which may pose a greater risk for KTRs due to their concurrent administration of immunosuppressive agents.³⁵ However, our meta-analysis observed that SGLT-2 inhibitors did not increase risk of serious infection, including UTIs, genital mycotic infection, and urosepsis, compared to the control group. Notably, a meta-analysis conducted by Li et al.,³⁶ evaluating UTIs and genital infections in non-transplant T2DM patients, revealed that only dapagliflozin 10 mg exhibited a significantly higher incidence of UTIs than placebo. In our analysis, only 20.6% of cases was prescribed with dapagliflozin. The overall infection rate of SGLT-2 inhibitors was comparable to that of the control group. Importantly, our study did not find an increase rate of genital infection with SGLT-2 inhibitors, unlike in non-transplant population.³⁶ This may be attributed to the effective routine post-transplant screening, care, and patient education in transplant clinics. Additionally, our meta-analysis demonstrated that SGLT-2 inhibitors did not increase the risk of DKA and graft rejection. Therefore, our findings shed new light on the safety profile of SGLT-2 inhibitors in kidney transplant recipients.

To the best of our knowledge, our meta-analysis included the most recent studies investigating the efficacy and safety outcomes of SGLT-2 inhibitors in KTRs. This encompasses both preexisting T2DM and PTDM status and is the first to assess mortality and cardiovascular outcomes, which was absent from previous meta-analysis.¹³ However, certain limitations must be acknowledged. Firstly, there are limited studies in our systematic review due to the lack of current studies in KTRs populations, which most existing studies are case series or observational designs without control groups. Secondly, there was significant heterogeneity among included studies, particularly in HbA1c, SBP, and UTI outcomes. This may result from the limited number of studies and the different types of studies for each outcome. Thirdly, the subgroup analysis based on study types (clinical trial vs cohort) and DM type (T2DM vs PTDM) could not be performed due to the limited available data in the included studies. Fourthly, the funnel plots for publication bias need to be interpreted with caution due to the limited number of included studies. Lastly, the follow-up duration in included studies might not have been sufficiently long to fully elucidate the potential renal benefits with SGLT-2 inhibitors.

Conclusion

SGLT-2 inhibitors have demonstrated significant benefits in reducing mortality and cardiovascular disease in diabetes KTRs. Furthermore, they effectively reduced HbA1c and BMI compared to controls, without increasing adverse events, including infections and allograft rejection. However, these agents did not show a significant benefit in kidney-related outcomes.

Ethical considerations

This study was approved by the Human Research Ethics Committee of Thammasat University (Medicine), which provided an exemption for this study (COE 243/2567).

Reporting guidelines

Zenodo: The Efficacy and Safety of SGLT2 Inhibitors in Diabetes Kidney Transplant Recipients: A Systematic Review and Meta-Analysis-supplemental materials and PRISMA checklist, DOI: https://doi.org/10.5281/zenodo.14928362.³⁷

The project contains the following reporting guidelines:

• PRISMA checklist
• Flow chart

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Data availability

No data are associated with this article.

Extended data

Zenodo: The Efficacy and Safety of SGLT2 Inhibitors in Diabetes Kidney Transplant Recipients: A Systematic Review and Meta-Analysis-supplemental materials and PRISMA checklist, DOI: https://doi.org/10.5281/zenodo.14988603.³⁷

This project contains the following extended data:

• Table S1 Search Terms
• Table S2 Risk of bias summary for included RCT
• Table S3 Graph and summary of Risk of Bias in Non-randomized Studies of Interventions (ROBIN-I) for included non-randomized controlled studies
• Figure S4 Funnel Plots of Standard Error on Kidney-Related Outcomes
• Figure S5 Funnel Plots of Standard Error on Metabolic Profiles
• Figure S6 Funnel Plots of Standard Error on Mortality and Cardiovascular Diseases
• Figure S7 Funnel Plots of Standard Error on Adverse Events

Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).

Acknowledgement

This study was supported by the Research Group in Nephrology and Renal Replacement Therapy from the Faculty of Medicine, Thammasat University. We also want to express our sincere gratitude to Dr. Prapasri Kulalert and Dr. Phichayut Phinyo for their invaluable advice and guidance and suggestions regarding the different stages of the meta-analysis presented in this manuscript.

References

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2. Cosio FG, Pesavento TE, Kim S, et al.: Patient survival after renal transplantation: IV. Impact of post-transplant diabetes. Kidney Int. 2002; 62(4): 1440–1446. PubMed Abstract | Publisher Full Text
3. Lin H, Yan J, Yuan L, et al.: Impact of diabetes mellitus developing after kidney transplantation on patient mortality and graft survival: a meta-analysis of adjusted data. Diabetol. Metab. Syndr. 2021; 13(1): 126. PubMed Abstract | Publisher Full Text | Free Full Text
4. Devine PA, Courtney AE, Maxwell AP: Cardiovascular risk in renal transplant recipients. J. Nephrol. 2019; 32(3): 389–399. PubMed Abstract | Publisher Full Text
5. Liefeldt L, Budde K: Risk factors for cardiovascular disease in renal transplant recipients and strategies to minimize risk. Transpl. Int. 2010; 23(12): 1191–1204. PubMed Abstract | Publisher Full Text
6. Cosio FG, Pesavento TE, Osei K, et al.: Post-transplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years. Kidney Int. 2001; 59(2): 732–737. PubMed Abstract | Publisher Full Text
7. Hjelmesaeth J, Hartmann A, Leivestad T, et al.: The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events. Kidney Int. 2006; 69(3): 588–595. PubMed Abstract | Publisher Full Text
8. Li CX, Liang S, Gao L, et al.: Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: A real-world systematic review and meta-analysis. PLoS One. 2021; 16(2): e0244689. PubMed Abstract | Publisher Full Text | Free Full Text
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11. McGuire DK, Shih WJ, Cosentino F, et al.: Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis. JAMA Cardiol. 2021; 6(2): 148–158. PubMed Abstract | Publisher Full Text | Free Full Text
12. Zelniker TA, Wiviott SD, Raz I, et al.: SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019; 393(10166): 31–39. PubMed Abstract | Publisher Full Text
13. Chewcharat A, Prasitlumkum N, Thongprayoon C, et al.: Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis. Med Sci (Basel). 2020; 8(4). Publisher Full Text
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15. Sterne JAC, Savovic J, Page MJ, et al.: RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366: l4898. Publisher Full Text
16. Sterne JA, Hernan MA, Reeves BC, et al.: ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355: i4919. Publisher Full Text
17. Demir ME, Ozler TE, Merhametsiz O, et al.: The results of SGLT-2 inhibitors use in kidney transplantation: 1-year experiences from two centers. Int. Urol. Nephrol. 2023; 55(11): 2989–2999. PubMed Abstract | Publisher Full Text | Free Full Text
18. Hisadome Y, Mei T, Noguchi H, et al.: Safety and Efficacy of Sodium-glucose Cotransporter 2 Inhibitors in Kidney Transplant Recipients With Pretransplant Type 2 Diabetes Mellitus: A Retrospective, Single-center, Inverse Probability of Treatment Weighting Analysis of 85 Transplant Patients. Transplant. Direct. 2021; 7(11): e772. PubMed Abstract | Publisher Full Text | Free Full Text
19. Lim JH, Kwon S, Jeon Y, et al.: The Efficacy and Safety of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients. Transplantation. 2022; 106(9): e404–e412. PubMed Abstract | Publisher Full Text
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21. Lim JH, Kwon S, Seo YJ, et al.: Cardioprotective Effect of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients: A Multicenter Propensity Score Matched Study. Kidney Int Rep. 2024; 9(8): 2474–2483. PubMed Abstract | Publisher Full Text | Free Full Text
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23. Schwaiger E, Burghart L, Signorini L, et al.: Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety. Am. J. Transplant. 2019; 19(3): 907–919. PubMed Abstract | Publisher Full Text | Free Full Text
24. Nuffield Department of Population Health Renal Studies GConsortium SiM-AC-RT: Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022; 400(10365): 1788–1801. PubMed Abstract | Publisher Full Text | Free Full Text
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26. EMPA-Kidney Collaborative Group: Empagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 2023; 388(2): 117–127. PubMed Abstract | Publisher Full Text | Free Full Text
27. Heerspink HJL, Stefansson BV, Correa-Rotter R, et al.: Dapagliflozin in Patients with Chronic Kidney Disease. N. Engl. J. Med. 2020; 383(15): 1436–1446. Publisher Full Text
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30. Oikonomaki D, Dounousi E, Duni A, et al.: Incretin based therapies and SGLT-2 inhibitors in kidney transplant recipients with diabetes: A systematic review and meta-analysis. Diabetes Res. Clin. Pract. 2021; 172: 108604. PubMed Abstract | Publisher Full Text
31. Li Z, Sun F, Zhang Y, et al.: Tacrolimus Induces Insulin Resistance and Increases the Glucose Absorption in the Jejunum: A Potential Mechanism of the Diabetogenic Effects. PLoS One. 2015; 10(11): e0143405. PubMed Abstract | Publisher Full Text | Free Full Text
32. Zheng H, Liu M, Li S, et al.: Sodium-Glucose Co-Transporter-2 Inhibitors in Non-Diabetic Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2021; 12: 706914. PubMed Abstract | Publisher Full Text | Free Full Text
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35. Karuthu S, Blumberg EA: Common infections in kidney transplant recipients. Clin. J. Am. Soc. Nephrol. 2012; 7(12): 2058–2070. Publisher Full Text
36. Li D, Wang T, Shen S, et al.: Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2017; 19(3): 348–355. PubMed Abstract | Publisher Full Text
37. Pattharanitima P, Anumas S: The Efficacy and Safety of SGLT2 Inhibitors in Diabetes Kidney Transplant Recipients: A Systematic Review and Meta-Analysis-supplemental materials and PRISMA checklist. Zenodo. 2025.

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Author details Author details

¹ Chulabhorn International College of Medicine, Klong Luang, Pathum Thani, 12120, Thailand
² Internal Medicine, Thammasat University, Klong Luang, Pathum Thani, 12120, Thailand
³ Department of Medicine, Mayo Clinic Minnesota, Rochester, Minnesota, 55905, USA

Kanachai Boonpiraks
Roles: Conceptualization, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Pajaree Krisanapan
Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Software, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Suthiya Anumas
Roles: Conceptualization, Formal Analysis, Funding Acquisition, Investigation, Methodology, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Charat Thongprayoon
Roles: Conceptualization, Formal Analysis, Methodology, Supervision, Writing – Review & Editing

Wisit Cheungpasitporn
Roles: Conceptualization, Formal Analysis, Methodology, Supervision, Writing – Review & Editing

Pattharawin Pattharanitima
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

The author(s) declared that no grants were involved in supporting this work.

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Boonpiraks K, Krisanapan P, Anumas S et al. The Efficacy and Safety of SGLT2 Inhibitors in Diabetes Kidney Transplant Recipients: A Systematic Review and Meta-Analysis [version 1; peer review: 1 approved]. F1000Research 2025, 14:329 (https://doi.org/10.12688/f1000research.162502.1)

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Reviewer Report 12 May 2025

Tarek Mahmoud, Jaber Al Ahmed Armed Forces Hospital, Subhan, Kuwait

Approved

https://doi.org/10.5256/f1000research.178712.r378428

Article Overview
This study aimed to evaluate the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in kidney transplant recipients (KTRs) with diabetes. After comprehensive literature search including observational and clinical trials they collected seven studies. There results ... Continue reading

Article Overview
This study aimed to evaluate the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in kidney transplant recipients (KTRs) with diabetes. After comprehensive literature search including observational and clinical trials they collected seven studies. There results indicated that SGLT2 inhibitors effectively reduced mortality, cardiovascular disease, HbA1c and BMI without increasing risk of infections and allograft rejection however it did not show clear benefit in kidney outcomes.
Strengths

The systematic review and meta-analysis helped to gather data randomly from the related studies reducing the bias and strengthening the findings.
The improvement in diabetes related and cardiovascular end-points supported the effectiveness of SGLT2 inhibitors in managing diabetes in KTRs.
The absence of serious adverse events, specifically the urinary tract and genital infections, supports the safety of SGLT2 inhibitors in this population.

Limitations

The majority of the included studies were case series and not randomized controlled ones, which is understandable from the available studies in the literature, but this may introduce bias and limit the generalizability of the results.
The criteria for selection may be tight to allow some more studies, specially early ones, to be included.
The selected studies have different designs and inclusion criteria which makes the comparison difficult.
The median follow-up period was 9 (9,12) months, which may not be enough to assess renal outcomes and detect long-term complications or benefits.

Clinical Implications
The study results support the benefits of SGLT2 inhibitors in managing diabetic KTRs with reasonable safety. However, the limitations highlight the need of larger randomized controlled trials including also non-diabetic KTRs with longer follow up duration to confirm these findings and lay down the guidelines for their use.
Conclusion
This systematic review and meta-analysis will add to the knowledge on the use of SGLT2i for KTRs. It should also stimulate further research to validate these findings and establish a comprehensive treatment guidelines.

N.B. in the title " ... Diabetes Kidney Transplant Recipients" It should be " ...Diabetic ..."

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

I cannot comment. A qualified statistician is required.
Are the conclusions drawn adequately supported by the results presented in the review?

Yes
If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.)

Yes

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Kidney transplantation, outcomes in special groups, diabetes, transplant infections, pregnancy, Ramadan Fast.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

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Tarek Mahmoud, Jaber Al Ahmed Armed Forces Hospital, Subhan, Kuwait

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Tarek Mahmoud, Jaber Al Ahmed Armed Forces Hospital, Subhan, Kuwait

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Approved

Article Overview
This study aimed to evaluate the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in kidney transplant recipients (KTRs) with diabetes. After comprehensive literature search including observational and clinical trials they collected seven studies. There results indicated that SGLT2 inhibitors effectively reduced mortality, cardiovascular disease, HbA1c and BMI without increasing risk of infections and allograft rejection however it did not show clear benefit in kidney outcomes.
Strengths

The systematic review and meta-analysis helped to gather data randomly from the related studies reducing the bias and strengthening the findings.
The improvement in diabetes related and cardiovascular end-points supported the effectiveness of SGLT2 inhibitors in managing diabetes in KTRs.
The absence of serious adverse events, specifically the urinary tract and genital infections, supports the safety of SGLT2 inhibitors in this population.

Limitations

The majority of the included studies were case series and not randomized controlled ones, which is understandable from the available studies in the literature, but this may introduce bias and limit the generalizability of the results.
The criteria for selection may be tight to allow some more studies, specially early ones, to be included.
The selected studies have different designs and inclusion criteria which makes the comparison difficult.
The median follow-up period was 9 (9,12) months, which may not be enough to assess renal outcomes and detect long-term complications or benefits.

Clinical Implications
The study results support the benefits of SGLT2 inhibitors in managing diabetic KTRs with reasonable safety. However, the limitations highlight the need of larger randomized controlled trials including also non-diabetic KTRs with longer follow up duration to confirm these findings and lay down the guidelines for their use.
Conclusion
This systematic review and meta-analysis will add to the knowledge on the use of SGLT2i for KTRs. It should also stimulate further research to validate these findings and establish a comprehensive treatment guidelines.

N.B. in the title " ... Diabetes Kidney Transplant Recipients" It should be " ...Diabetic ..."

Are the rationale for, and objectives of, the Systematic Review clearly stated?

Yes
Are sufficient details of the methods and analysis provided to allow replication by others?

Yes
Is the statistical analysis and its interpretation appropriate?

I cannot comment. A qualified statistician is required.
Are the conclusions drawn adequately supported by the results presented in the review?

Yes
If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.)

Yes

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Kidney transplantation, outcomes in special groups, diabetes, transplant infections, pregnancy, Ramadan Fast.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Respond to this report

Responses (0)

[1] 1. Cosio FG, Hickson LJ, Griffin MD, et al.: Patient survival and cardiovascular risk after kidney transplantation: the challenge of diabetes. Am. J. Transplant. 2008; 8(3): 593–599. PubMed Abstract | Publisher Full Text

[2] 2. Cosio FG, Pesavento TE, Kim S, et al.: Patient survival after renal transplantation: IV. Impact of post-transplant diabetes. Kidney Int. 2002; 62(4): 1440–1446. PubMed Abstract | Publisher Full Text

[3] 3. Lin H, Yan J, Yuan L, et al.: Impact of diabetes mellitus developing after kidney transplantation on patient mortality and graft survival: a meta-analysis of adjusted data. Diabetol. Metab. Syndr. 2021; 13(1): 126. PubMed Abstract | Publisher Full Text | Free Full Text

[4] 4. Devine PA, Courtney AE, Maxwell AP: Cardiovascular risk in renal transplant recipients. J. Nephrol. 2019; 32(3): 389–399. PubMed Abstract | Publisher Full Text

[5] 5. Liefeldt L, Budde K: Risk factors for cardiovascular disease in renal transplant recipients and strategies to minimize risk. Transpl. Int. 2010; 23(12): 1191–1204. PubMed Abstract | Publisher Full Text

[6] 6. Cosio FG, Pesavento TE, Osei K, et al.: Post-transplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years. Kidney Int. 2001; 59(2): 732–737. PubMed Abstract | Publisher Full Text

[7] 7. Hjelmesaeth J, Hartmann A, Leivestad T, et al.: The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events. Kidney Int. 2006; 69(3): 588–595. PubMed Abstract | Publisher Full Text

[8] 8. Li CX, Liang S, Gao L, et al.: Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: A real-world systematic review and meta-analysis. PLoS One. 2021; 16(2): e0244689. PubMed Abstract | Publisher Full Text | Free Full Text

[9] 9. Li N, Lv D, Zhu X, et al.: Effects of SGLT2 Inhibitors on Renal Outcomes in Patients With Chronic Kidney Disease: A Meta-Analysis. Front Med (Lausanne). 2021; 8: 728089. PubMed Abstract | Publisher Full Text | Free Full Text

[10] 10. Zinman B, Wanner C, Lachin JM, et al.: Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N. Engl. J. Med. 2015; 373(22): 2117–2128. Publisher Full Text

[11] 11. McGuire DK, Shih WJ, Cosentino F, et al.: Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis. JAMA Cardiol. 2021; 6(2): 148–158. PubMed Abstract | Publisher Full Text | Free Full Text

[12] 12. Zelniker TA, Wiviott SD, Raz I, et al.: SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019; 393(10166): 31–39. PubMed Abstract | Publisher Full Text

[13] 13. Chewcharat A, Prasitlumkum N, Thongprayoon C, et al.: Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis. Med Sci (Basel). 2020; 8(4). Publisher Full Text

[14] 14. Page MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71. Publisher Full Text

[15] 15. Sterne JAC, Savovic J, Page MJ, et al.: RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366: l4898. Publisher Full Text

[16] 16. Sterne JA, Hernan MA, Reeves BC, et al.: ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355: i4919. Publisher Full Text

[17] 17. Demir ME, Ozler TE, Merhametsiz O, et al.: The results of SGLT-2 inhibitors use in kidney transplantation: 1-year experiences from two centers. Int. Urol. Nephrol. 2023; 55(11): 2989–2999. PubMed Abstract | Publisher Full Text | Free Full Text

[18] 18. Hisadome Y, Mei T, Noguchi H, et al.: Safety and Efficacy of Sodium-glucose Cotransporter 2 Inhibitors in Kidney Transplant Recipients With Pretransplant Type 2 Diabetes Mellitus: A Retrospective, Single-center, Inverse Probability of Treatment Weighting Analysis of 85 Transplant Patients. Transplant. Direct. 2021; 7(11): e772. PubMed Abstract | Publisher Full Text | Free Full Text

[19] 19. Lim JH, Kwon S, Jeon Y, et al.: The Efficacy and Safety of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients. Transplantation. 2022; 106(9): e404–e412. PubMed Abstract | Publisher Full Text

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The Efficacy and Safety of SGLT2 Inhibitors in Diabetes Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

Abstract

Background

Methods

Results

Conclusions

Keywords

Introduction

Methods

Search strategy and selection criteria

Data extraction and quality assessment

Statistical analysis

Results

Study characteristics

Figure 1. PRISMA flow of search methodology and selection process.

Table 1. Characteristics of the Included Studies.

Efficacy of SGLT-2 inhibitors on kidney-related outcomes

Figure 2. Forest plots of the efficacy of SGLT-2 inhibitors on kidney-related outcomes.

Efficacy of SGLT-2 inhibitors on metabolic profiles

Figure 3. Forest plots of the efficacy of SGLT-2 inhibitors on metabolic profiles.

Efficacy of SGLT-2 inhibitors on all-cause mortality and cardiovascular diseases

Figure 4. Forest plots of the efficacy of SGLT-2 inhibitors on mortality and CVD.

Adverse events of SGLT-2 inhibitors

Figure 5. Forest plots of the adverse events of SGLT-2 inhibitors.

Evaluation of publication bias

Discussion

Conclusion

Ethical considerations

Reporting guidelines

Data availability

Extended data

Acknowledgement

References

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