SGLT-2is Mitigate Risk of Cardiovascular, Kidney Diseases in Patients with Type 2 Diabetes and AKD

Heng-Chih Pan, MD

Credit: ResearchGate

Findings from a recent study are underscoring the importance of sodium-glucose cotransport protein 2 inhibitors (SGLT-2is) for managing acute kidney injury (AKI) and mitigating the risks of major cardiovascular and kidney diseases in patients with type 2 diabetes and acute kidney disease (AKD).

Using global healthcare data from the TriNetX database to compare outcomes in SGLT-2i users and nonusers, investigators found administration of SGLT-2is was associated with significant reductions in all-cause mortality, major adverse kidney events (MAKEs), and major adverse cardiovascular events (MACEs) when compared with nonuse.¹

The US Centers for Disease Control and Prevention estimates 1 in 3 adults with diabetes has chronic kidney disease. According to the National Kidney Foundation, people with kidney disease and type 2 diabetes are 3 times more likely to die from a heart attack or stroke than people with type 2 diabetes alone. SGLT-2is prevent the reabsorption of filtered glucose from the tubular lumen to improve blood sugar control in people with type 2 diabetes and have been shown to improve kidney-related and cardiovascular outcomes, alluding to potential protective benefits in patients with type 2 diabetes and AKD.^2,3

“With the increasing incidence of AKI among hospitalized patients in various settings, AKD is also becoming increasingly prevalent,” wrote Heng-Chih Pan, MD, of Keelung Chang Gung Memorial Hospital in Taiwan, and colleagues.¹ “Thus, effective management of AKD is vital to prevent further kidney damage and adverse outcomes.”

To examine the long-term associations of SGLT-2is with outcomes among patients with type 2 diabetes and AKD, investigators leveraged data from the TriNetX database, a global health collaborative clinical research platform, from September 30, 2002, to September 30, 2022. Patients from 76 healthcare organizations encompassing hospitals, primary care units, and specialists were included in the study. To be eligible for inclusion, patients were required to be 18-90 years of age, have a diagnosis of type 2 diabetes, and receive dialysis during hospitalization.¹

Applying these criteria, investigators enrolled 230,366 patients in the study, dividing the cohort into 2 groups based on receipt of a prescription for an SGLT-2i during the study period: the SGLT-2i group (n = 5319) and the nonuser group (n = 225,047). Propensity score matching was used to select a cohort of patients based on age, sex, race and ethnicity, comorbidities, medications, and laboratory data. In total, 5317 SGLT-2i users were matched to 5317 nonusers.¹

Follow-up was conducted with a maximum duration of 5 years or until the occurrence of an outcome or death. The primary outcome was mortality, and the secondary outcomes were MAKEs, defined as redialysis, dialysis dependence, or mortality, and MACEs, defined as cerebral infarction, hemorrhagic stroke, acute myocardial infarction, cardiogenic shock, or mortality.¹

The 5-year all-cause mortality rate was 9.0% in the SGLT-2i group and 18.7% in the control group. Upon analysis, use of SGLT-2is was associated with a lower mortality rate (Adjusted hazard ratio [aHR], 0.69; 95% Confidence interval [CI], 0.62-0.77). Investigators also observed a decreased risk of MAKEs in the SGLT-2i group (9.5%) compared with the control group (21.0%; aHR, 0.62; 95% CI, 0.56-0.69), as well as a lower risk of MACEs (13.5% for SGLT-2i vs 25.8% for control; aHR, 0.75; 95% CI, 0.65-0.88).¹

Of note, the risk reduction associated with SGLT-2is remained significant even among patients without hypertension (Adjusted odds ratio [aOR], 0.67; 95% CI, 0.59-0.76), those with advanced chronic kidney disease (aOR for eGFR 45 mL/min/1.73 m2, 0.73; 95% CI, 0.64-0.84), and those not receiving other hypoglycemic agents (aOR for metformin, 0.60; 95% CI, 0.51-0.71).¹

Findings were also validated in an external cohort of 1233 patients with type 2 diabetes and AKD from the Chang Gung Research Database. In this analysis, SGLT-2i use was associated with a significantly lower risk of mortality (aHR, 0.43; 95% CI, 0.21-0.86; P = .02), MAKEs (aHR, 0.39; 95% CI, 0.24-0.63; P < .001), and MACEs (aHR, 0.47; 95% CI, 0.29-0.75; P = .002) compared with the control group.¹

“These findings highlight the potential benefit of SGLT-2is and suggest that clinicians should consider incorporating them into the management of type 2 diabetes with AKD,” investigators concluded.¹

References:

1. Pan H, Chen J, Chen H, et al. Sodium-Glucose Cotransport Protein 2 Inhibitors in Patients With Type 2 Diabetes and Acute Kidney Disease. JAMA Netw Open. 2024;7(1):e2350050. doi:10.1001/jamanetworkopen.2023.50050
2. US Centers for Disease Control and Prevention. Chronic Kidney Disease (CKD). Diabetes. December 30, 2022. Accessed January 3, 2023. https://www.cdc.gov/diabetes/managing/diabetes-kidney-disease.html
3. National Kidney Foundation. Does Type 2 Diabetes Increase Your Risk for Kidney Disease? Yes. Accessed January 3, 2023. https://www.kidney.org/atoz/content/does-type-2-diabetes-increase-your-risk-kidney-disease-yes