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Cardiovascular and Kidney Outcomes following Sodium-Glucose Cotransporter 2 Inhibitor Initiation in CKD: A Swedish
Joakim Österman1, Ehab Al-Sodany1, Peter Hemmingsson1
1Department of Clinical Intervention and Technology (CLINTEC), Renal Medicine, Karolinska Institutet, Huddinge, Sweden.
Key Points:
In nationwide nephrology-referred CKD, sodium-glucose cotransporter 2 inhibitor use was associated with lower cardiovascular event and KRT risk. Associations with cardiovascular events and KRT were consistent in advanced CKD, a group underrepresented in trials. Findings supported the applicability of trial results to a broad nephrology-referred CKD population.
Background:
Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) reduce cardiovascular (CV) and kidney events in randomized trials, yet evidence on their effectiveness in routine nephrology practice remains limited. We examined CV and kidney outcomes associated with SGLT2 inhibitor initiation in adults with CKD receiving specialist nephrology care.
Methods:
In this nationwide cohort study, we included adults with CKD receiving specialist nephrology care, identified through the Swedish Renal Registry between January 1, 2016, and December 31, 2023. Participants had baseline data on eGFR, urine albumin-to-creatinine ratio, and hemoglobin; those with prior KRT were excluded. Follow-up continued until December 31, 2024. SGLT2 inhibitor use was identified through national pharmacy records and analyzed according to an intention-to-treat approach. Outcomes were major adverse cardiovascular events (MACE), initiation of KRT, all-cause mortality, and a composite of heart failure hospitalization or CV death. Associations were estimated using inverse probability-weighted marginal structural models to address time-dependent confounding.
Results:
Among 32,856 participants (median age 73 years [interquartile range, 63-79]; 36% women; mean eGFR 29.3±16.8 ml/min per 1.73 m 2 ), 1493 (4.5%) were prevalent SGLT2 inhibitor users at baseline and 3491 (10.6%) initiated treatment during follow-up (4984 ever-exposed, 15.2%). SGLT2 inhibitor use was associated with a lower risk of MACE (odds ratio 0.80, 95% confidence interval, 0.71 to 0.91) and KRT (0.67, 0.52 to 0.85). No associations were observed for all-cause mortality (0.95, 0.79 to 1.15) or the composite heart failure outcome (0.87, 0.65 to 1.16), although a lower risk was observed in the incident-user analysis (0.61, 0.38 to 0.98). Associations were generally consistent across prespecified subgroups.
Conclusions:
In adults with CKD managed in specialist nephrology care, SGLT2 inhibitor use was associated with a lower risk of MACE and KRT, extending randomized trial evidence to a broad, real-world CKD population.
Insights
Sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly lowered major adverse cardiovascular events and kidney replacement therapy initiation in adults with chronic kidney disease (CKD). This real-world study confirms SGLT2 inhibitors
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Randomized trials show Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular and kidney events.
- Evidence on SGLT2 inhibitor effectiveness in routine nephrology practice is limited.
- This study examines SGLT2 inhibitor initiation outcomes in adults with chronic kidney disease (CKD) under specialist care.
Purpose of the Study:
- To evaluate the real-world effectiveness of SGLT2 inhibitors in adults with CKD.
- To assess the association of SGLT2 inhibitor use with major adverse cardiovascular events (MACE) and kidney replacement therapy (KRT).
- To extend findings from randomized trials to a broader CKD population in specialist care.
Main Methods:
- Nationwide cohort study using the Swedish Renal Registry (2016-2023).
- Included adults with CKD receiving specialist nephrology care, excluding those with prior KRT.
- Analyzed SGLT2 inhibitor use via pharmacy records using inverse probability-weighted marginal structural models.
Main Results:
- SGLT2 inhibitor use was associated with a lower risk of MACE (OR 0.80) and KRT initiation (OR 0.67).
- No significant association was found for all-cause mortality or a composite heart failure outcome.
- A reduced risk for the composite HF outcome was observed in incident-user analysis (OR 0.61).
Conclusions:
- SGLT2 inhibitor use in adults with CKD managed in specialist care is linked to reduced MACE and KRT initiation.
- These findings support the use of SGLT2 inhibitors in real-world CKD management.
- The study extends the evidence base for SGLT2 inhibitors beyond randomized controlled trials.
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