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Sodium-Glucose Co-Transporter-2 Inhibitors and Cardiovascular Effects in Kidney Transplant Recipients With Diabetes
Idit Dotan1, Amir Polansky1, Idan Bergman2
1Institute of Endocrinology, Diabetes and Metabolism, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel; Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Objectives:
Sodium-glucose co-transporter-2 inhibitors (SGLT2is) reduce major adverse cardiovascular events and mortality in patients with type 2 diabetes mellitus, but kidney transplant recipients (KTRs), a high-risk group, were excluded from major trials. We aimed to evaluate the association between SGLT2i use and cardiovascular outcomes in KTRs with diabetes.
Methods:
In this retrospective matched-cohort study at a large transplant center, KTRs with diabetes treated with SGLT2i were compared to matched controls receiving other antihyperglycemic agents. Major outcomes were: (1) a composite of acute coronary syndrome, stroke/transient ischemic attack, or all-cause mortality; and (2) a composite of heart failure hospitalizations (hHFs) or all-cause mortality.
Results:
A total of 480 patients (240 per group; 20% women; median age 63-64 years) were included. Treatment with SGLT2i was started 5.9 years (IQR 2.0-13.9) after the transplant surgery, and patients were followed for up to 3 years. The incidence of acute coronary syndrome, stroke/transient ischemic attack, or death was 7.9 vs 13.6 events per 100 person-years in the SGLT2i and control groups, respectively (adjusted hazard ratio 0.64, 95% confidence interval 0.42-0.97, P = .039). HHFs or death occurred less frequently in SGLT2i users (5.7 vs 11.6 events per 100 person-years), though the difference was not statistically significant after adjustment (hazard ratio 0.82, 95% confidence interval 0.50-1.32, P = .410).
Conclusions:
SGLT2i use was associated with lower rates of major cardiovascular events in KTRs with diabetes, without a significant reduction in hHF. Given the elevated cardiovascular risk in KTRs, these findings support further investigation of SGLT2i therapy in this population.
Insights
Sodium-glucose cotransporter-2 (SGLT2) inhibitor use in kidney transplant recipients with diabetes was linked to fewer major cardiovascular events. Further research is recommended for this high-risk group.
Area of Science:
- Cardiology
- Nephrology
- Endocrinology
Background:
- Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are proven to reduce cardiovascular events and mortality in type 2 diabetes mellitus (T2DM).
- Kidney transplant recipients (KTRs) with diabetes represent a population at high risk for cardiovascular events, yet were excluded from major SGLT2i trials.
Purpose of the Study:
- To evaluate the association between SGLT2 inhibitor use and cardiovascular outcomes in diabetic kidney transplant recipients.
Main Methods:
- A retrospective matched-cohort study compared diabetic KTRs treated with SGLT2i to those receiving other antihyperglycemic agents.
- Major outcomes included a composite of acute coronary syndrome (ACS), stroke/transient ischemic attack (TIA), or all-cause mortality, and a composite of heart failure hospitalizations or all-cause mortality.
Main Results:
- The study included 480 patients (240 per group), with SGLT2i initiation a median of 5.9 years post-transplant.
- SGLT2i use was associated with a significantly lower incidence of ACS, stroke/TIA, or death (adjusted HR 0.64; p=0.039).
- A trend towards fewer heart failure hospitalizations or deaths was observed in the SGLT2i group, but did not reach statistical significance (adjusted HR 0.82; p=0.410).
Conclusions:
- SGLT2 inhibitor therapy is associated with reduced major cardiovascular events in kidney transplant recipients with diabetes.
- While not statistically significant, a potential benefit regarding heart failure hospitalizations warrants further investigation.
- Given the high cardiovascular risk in KTRs, SGLT2i therapy merits further study in this population.
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01:27Glucose Transporters
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes: