Sodium–Glucose Cotransporter-2 Inhibitors and the Risk for Dialysis and Cardiovascular Disease in Patients With Stage 5 Chronic Kidney Disease
Publication: Annals of Internal Medicine
Visual Abstract. Sodium–Glucose Cotransporter-2 Inhibitors and the Risk for Dialysis and Cardiovascular Disease in Patients With Stage 5 Chronic Kidney Disease
Current guidelines support the initiation of a sodium–glucose cotransporter-2 inhibitor (SGLT2i) in patients with diabetes mellitus who have chronic kidney disease with an estimated glomerular filtration rate (eGFR) of 20 mL/min/1.73 m2 or greater. However, these guidelines do not address whether similar patients with an eGFR less than 20 mL/min/1.73 m2 should start receiving an SGLT2i because the randomized controlled trials supporting the guidelines did not include persons with eGFR levels that low. This article describes an observational study that emulated such a trial and reports outcomes that include the risk for dialysis, cardiovascular events, and all-cause mortality.
Abstract
Background:
No studies have reported the long-term outcomes of initiating sodium–glucose cotransporter-2 inhibitors (SGLT2is) in patients with estimated glomerular filtration rates less than 20 mL/min/1.73 m2 to predialysis.
Objective:
To compare the risk for dialysis, cardiovascular events, and death between SGLT2i users and nonusers in patients with type 2 diabetes (T2D) and stage 5 chronic kidney disease (CKD).
Design:
Target trial emulation study.
Setting:
Taiwan’s National Health Insurance Research Database (NHIRD).
Participants:
By applying sequential target trial emulation principle, 23 854 SGLT2i users and 23 892 SGLT2i nonusers were selected from the NHIRD for patients with T2D and stage 5 CKD from 1 May 2016 to 31 October 2021.
Measurements:
Conditional Cox proportional hazards models were used to compare the risks for dialysis, hospitalization for heart failure, acute myocardial infarction (AMI), diabetic ketoacidosis (DKA), acute kidney injury (AKI), and all-cause mortality between SGLT2i users and nonusers.
Results:
In the intention-to-treat model, compared with no SGLT2i use, SGLT2i use was associated with lower risks for dialysis (hazard ratio [HR], 0.34 [95% CI, 0.27 to 0.43]), hospitalization for heart failure (HR, 0.80 [CI, 0.73 to 0.86]), AMI (HR, 0.61 [CI, 0.52 to 0.73]), DKA (HR, 0.78 [CI, 0.71 to 0.85]), and AKI (HR, 0.80 [CI, 0.70 to 0.90]), but there was no difference in the risk for all-cause mortality (HR, 1.11 [CI, 0.99 to 1.24]). The Kaplan–Meier curves and subgroup analyses also showed that initiation of an SGLT2i in stage 5 CKD was associated with a lower risk for long-term dialysis than no SGLT2i use.
Limitation:
This result may not apply to patients without T2D.
Conclusion:
This emulated target trial showed that SGLT2i use was associated with a lower risk for dialysis, cardiovascular events, DKA, and AKI than no SGLT2i use in patients with T2D and stage 5 CKD.
Primary Funding Source:
National Health Research Institutes, Taiwan.
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Information & Authors
Information
Published In
Annals of Internal Medicine
History
Published online: 30 April 2024
Keywords
- Cardiovascular diseases
- Chronic kidney disease
- Coronary heart disease
- Glomerular filtration rate
- Heart diseases
- Heart failure
- Hospital medicine
- Medical dialysis
- Mortality
- Myocardial infarction
- Nephrology
- Population statistics
- Prevention, policy, and public health
- Renal diseases
- Renal physiology
- Vital statistics
Copyright
© 2024 American College of Physicians.
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Sodium–Glucose Cotransporter-2 Inhibitors and the Risk for Dialysis and Cardiovascular Disease in Patients With Stage 5 Chronic Kidney Disease. Ann Intern Med. [Epub 30 April 2024]. doi:10.7326/M23-1874
Sodium–Glucose Cotransporter-2 Inhibitors and the Risk for Dialysis and Cardiovascular Disease in Patients With Stage 5 Chronic Kidney Disease. Ann Intern Med. [Epub 30 April 2024]. doi:10.7326/M23-1874
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