#1254 SGLT-2 inhibitors in patients with type 2 diabetes with acute kidney disease
Authors: Wu Vin-Cent , Pan Heng-Chih , Chen Jui-Yi 
Published: May 2024

Abstract

Background and Aims
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been observed to exhibit correlative relationships with favorable impacts on renal and cardiovascular outcomes among individuals diagnosed with type 2 diabetes. Nonetheless, the extent of the influence of SGLT-2 inhibitors on patients with type 2 diabetes concomitant with acute kidney disease (AKD) remains enigmatic.

Method
This investigation leveraged expansive global healthcare data from TriNetX, spanning the timeframe from September 2002 to September 2022. Propensity score matching was systematically applied to meticulously curate a patient cohort, with a subsequent follow-up period extending over 5 years or until the manifestation of a defined outcome or mortality. The underlying research design took the form of an observational cohort study.
The primary objective of this study was to scrutinize the enduring associations of Sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients afflicted with type 2 diabetes and concurrent acute kidney disease (AKD). Particular emphasis was directed towards evaluating the impact on mortality rates, major adverse kidney events (MAKEs), and major adverse cardiovascular events (MACEs) over the specified temporal continuum.
The primary outcomes measured were mortality, MAKEs, and MACEs. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were calculated to compare the risks between SGLT-2 inhibitor users and non-users, representing the average treatment effect among the treated.

Results
A total cohort of 230, 366 individuals diagnosed with AKD, boasting a mean age of 67.1 years and a male representation of 53.1%, formed the basis of this study. Within this cohort, 5 319 subjects (constituting 2.3%) were identified as users of SGLT-2 inhibitors. The incidence rates for mortality, MAKEs, and MACEs among non-users were recorded at 18.7%, 21.0%, and 25.8%, respectively.
Following the meticulous application of propensity score matching, absolute differences in the incidence rates of mortality, MAKEs, and MACEs between SGLT-2 inhibitor users and non-users were calculated at 9.7%, 11.5%, and 12.3%, respectively. In the treated population, SGLT-2 inhibitor users exhibited a notably lower risk of mortality (adjusted Hazard Ratio [aHR]: 0.69, 95% Confidence Interval [CI]: 0.62-0.77), MAKEs (aHR: 0.62, 95% CI: 0.56-0.69), and MACEs (aHR: 0.75, 95% CI: 0.65-0.88) in comparison to their non-using counterparts.
The robustness of these observed benefits was validated externally using a multicenter cohort dataset comprising 1, 233 AKD patients who were SGLT-2 inhibitor users, thereby affirming the positive outcomes. Importantly, the risk reduction associated with SGLT-2 inhibitors persisted significantly even among subpopulations devoid of hypertension, those with advanced chronic kidney disease, and individuals not concurrently receiving other oral hypoglycemic agents.

Conclusion
In this meticulously conducted cohort study involving individuals diagnosed with type 2 diabetes and AKD receiving treatment with SGLT-2 inhibitors, our findings suggest a potential association with diminished rates of mortality, MAKEs, and MACEs. These results underscore the imperative for subsequent and more in-depth investigations into the precise associations of SGLT-2 inhibitors within this distinctively treated population.