The outcomes of SGLT-2 inhibitor utilization in diabetic kidney transplant recipients

Abstract

Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) have demonstrated efficacy in reducing cardiovascular events and potentially improving kidney function in diabetic patients. This investigation analyzes the TriNetX database to assess the efficacy of SGLT-2i in diabetic kidney transplant recipients (KTR) concerning all-cause mortality, major adverse cardiac events (MACE), and major adverse kidney events (MAKE). The study includes type 2 diabetic patients over 18 who underwent kidney transplants between June 1, 2015, and June 1, 2023, with a focus on SGLT-2i use within the first three months post-transplant. After propensity score matching, the study compares 1970 SGLT-2i users with matched non-users. With a median follow-up of 3.4 years, SGLT-2i users showed significantly lower rates of all-cause mortality (adjusted hazard ratio [aHR]: 0.32), MACE (aHR: 0.48), and MAKE (aHR: 0.52). These findings indicate that SGLT-2i significantly reduces mortality and adverse events in diabetic KTR, underscoring its potential to improve post-transplant outcomes.

Fig. 1. Algorithm for patient selection and enrollment in the study.

SGLT-2i, sodium-glucose cotransporter 2 inhibitor.

Fig. 2. Assessment of primary and secondary outcomes, specificity analysis, and outcome controls in SGLT-2i users (n = 1970) versus non-users (n = 1970) among diabetic KTR.

aHRs and 95% CIs are presented, with the centre defined as the aHR and error bars representing the CIs. The vertical line indicates an aHR of 1.00. ACEi angiotensin-converting enzyme inhibitor; AKI acute kidney injury; aHR adjusted hazard ratio; AMI acute myocardial infarction; ARB angiotensin II receptor blocker; CI confidence interval; KTR kidney transplant recipient; MACE major adverse cardiovascular event; MAKE major adverse kidney event; SGLT-2i sodium-glucose cotransporter 2 inhibitor; UTI urinary tract infection; Vit.C vitamin C.

Fig. 3. Subgroup analysis.

Forest plots of aHRs for SGLT-2i users (n = 1,970) versus non-users (n = 1,970) after kidney transplant, regarding the long-term risks assessed in a sensitivity analysis for all-cause mortality, MACE, and MAKE. aHRs and 95% CIs are presented, with the centre defined as the aHR and error bars representing the CIs. The vertical line indicates an aHR of 1.00. Baseline characteristics were assessed based on data collected from one year before and up to the day before the index date; medication usage was evaluated within the initial 90 days following the index date. Definitions for SGLT-2i user types and dosages are as follows: A ‘Long-term SGLT-2i user’ is defined as a patient who was already using SGLT-2i before the transplant, whereas a ‘New SGLT-2i user’ refers to a patient who began using SGLT-2i after their transplant. Regarding dosage, ‘Low dose SGLT-2i’ includes dapagliflozin 5 mg/once daily, canagliflozin 100 mg/once daily, empagliflozin 10 mg/once daily, or ertugliflozin 5 mg/once daily. ‘High dose SGLT-2i’ is defined as dapagliflozin 10 mg/once daily, canagliflozin 300 mg/once daily, empagliflozin 25 mg/once daily, or ertugliflozin 15 mg/once daily. ACEi angiotensin-converting enzyme inhibitor; aHR adjusted hazard ratio; ARB angiotensin II receptor blocker; BMI body mass index; CI confidence interval; eGFR estimated glomerular filtration rate; HbA1c hemoglobin A1c; MACE major adverse cardiovascular event; MAKE major adverse kidney event; MMF mycophenolate mofetil; SGLT-2i sodium-glucose cotransporter 2 inhibitor.