Effects of RAS and SGLT2 inhibitors alone or in combination on end-stage kidney disease and/or all-cause death in patients with both diabetes and hypertension: a nationwide cohort study.

Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE

Original Publication: London : BioMed Central, [2002-

Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use ; Sodium-Glucose Transporter 2 Inhibitors*/adverse effects ; Kidney Failure, Chronic*/mortality ; Kidney Failure, Chronic*/diagnosis ; Kidney Failure, Chronic*/prevention & control ; Hypertension*/drug therapy ; Hypertension*/mortality ; Hypertension*/diagnosis ; Hypertension*/physiopathology ; Diabetes Mellitus, Type 2*/drug therapy ; Diabetes Mellitus, Type 2*/mortality ; Diabetes Mellitus, Type 2*/diagnosis ; Diabetic Nephropathies*/mortality ; Diabetic Nephropathies*/diagnosis ; Diabetic Nephropathies*/prevention & control ; Diabetic Nephropathies*/drug therapy ; Renin-Angiotensin System*/drug effects ; Angiotensin Receptor Antagonists*/therapeutic use ; Angiotensin Receptor Antagonists*/adverse effects ; Angiotensin-Converting Enzyme Inhibitors*/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors*/adverse effects ; Antihypertensive Agents*/therapeutic use ; Antihypertensive Agents*/adverse effects; Humans ; Male ; Female ; Middle Aged ; Aged ; Risk Factors ; Treatment Outcome ; Republic of Korea/epidemiology ; Databases, Factual ; Time Factors ; Risk Assessment ; Cause of Death ; Drug Therapy, Combination ; Retrospective Studies

Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the Institutional Review Board of the Kangbuk Samsung Hospital (KBSMC 2022-04-016), which waived the requirement for informed consent due to the use of deidentified data. Consent for publication: Not applicable. Competing interests: None.
Background: Renin-angiotensin-aldosterone system (RAS) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors are key treatments for diabetic kidney disease. However, their independent and combined effects on end-stage kidney disease (ESKD) and mortality remain unclear. This study evaluates their impact, alone or in combination, on ESKD and all-cause mortality in patients with diabetes and hypertension.
Methods: A nationwide cohort study using the Korean National Health Database included 261,783 individuals with type 2 diabetes and hypertension (2015-2017). Participants were grouped into (1) no RAS or SGLT2 inhibitors (reference), (2) SGLT2 inhibitors alone, (3) RAS inhibitors alone, and (4) combination therapy. Cox regression models were used to estimate hazard ratios (HRs) for ESKD, mortality, and their composite.
Results: Over 5.38 years, 2,674 (1.02%) developed ESKD and 20,866 (7.97%) died. Combination therapy showed the greatest risk reduction for composite outcomes [HR 0.68, 95% confidence interval (CI) 0.56-0.82] and mortality (HR 0.68, 95% CI 0.56-0.83). SGLT2 inhibitors alone reduced composite risk (HR 0.71, 95% CI 0.61-0.84) and mortality (HR 0.68, 95% CI 0.57-0.81). RAS inhibitors alone had modest effects (HR 0.96, 95% CI 0.93-0.98) on composite outcomes and mortality (HR 0.94, 95% CI 0.91-0.97). Notably, only combination therapy was associated with lower ESKD risk (HR 0.63, 95% CI 0.37-1.07), but this was not statistically significant. SGLT2 inhibitors consistently reduced ESKD and mortality, while RAS inhibitors were beneficial mainly in non-SGLT2 inhibitor users.
Conclusion: Combination therapy may provide the greatest renal and survival benefit for diabetic patients with hypertension. SGLT2 inhibitors alone significantly reduced mortality, while RAS inhibitors alone had a modest impact.
(© 2025. The Author(s).)

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Keywords: All-cause mortality; Chronic kidney disease; End-stage kidney disease; Hypertension; Renin-angiotensin system inhibitors; Sodium-glucose cotransporter-2 inhibitors; Type 2 diabetes

0 (Sodium-Glucose Transporter 2 Inhibitors)
0 (Angiotensin Receptor Antagonists)
0 (Angiotensin-Converting Enzyme Inhibitors)
0 (Antihypertensive Agents)

Date Created: 20250714 Date Completed: 20250715 Latest Revision: 20250718

20250718

PMC12257671

10.1186/s12933-025-02846-x

40660221