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Updated: Jan 3, 2026
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
The Effects of SGLT2 Inhibitors on Cardiovascular and Renal Outcomes in Diabetic Patients: A Systematic Review and
Kevin Bryan Lo1, Fahad Gul2, Pradhum Ram3
1Department of Medicine, Einstein Medical Center, Philadelphia, Pennsylvania, USA, lokevinmd@gmail.com.
Background:
Previous meta-analyses demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) primarily on patients with established atherosclerotic cardiovascular disease (ASCVD), but with questionable efficacy on patients at risk of ASCVD. Additionally, evidence of beneficial cardiorenal outcomes in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 with the CV outcomes trials remains unclear. Canagliflozin, one of the SGLT2i, has recently been studied in a large randomized controlled trial in diabetic patients with chronic kidney disease. Thus, there is a need to understand the combined outcomes on the population targeted for treatment with SGLT2i as a whole, regardless of ASCVD status. This meta-analysis will therefore assess the efficacy of SGLT2i in cardiovascular and renal outcomes in general, and in patients with eGFR under 60 mL/min/1.73 m2 in particular.
Methods:
We searched PubMed and Cochrane databases for randomized, placebo-controlled studies involving SGLT2i. We examined composite cardiovascular outcomes of death from cardiovascular causes, nonfatal myocardial infarctions, nonfatal stroke, and heart failure hospitalizations. Renal composite outcomes and progression of albuminuria were also analyzed. Pooled relative risks (RR) and their 95% confidence intervals (CI) were calculated using a fixed-effects model.
Results:
The search yielded a total of 252 articles. Four studies were ultimately included in the meta-analysis after exclusion of other irrelevant studies. The pooled RR (95% CI) for the composite cardiovascular outcome was 0.93 (0.87-0.99) with a number needed to treat (NNT) of 167 in the general study population and 0.89 (0.77-1.02) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for all-cause mortality was 0.9 (0.84-0.97) with NNT = 143. The pooled RR for death from cardiovascular causes alone was 0.89 (0.81-0.99) in the general population and 0.82 (0.62-1.07) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for heart failure hospitalizations was 0.71 (0.63-0.79) with NNT = 91. With respect to renal outcomes, the pooled RR for the composite renal outcome was 0.63 (0.56-0.71) with NNT = 67; this was true even in patients with eGFR <60 mL/min/1.73 m2 0.67 (0.59-0.76). Lastly, the pooled RR for progression of albuminuria was 0.80 (0.76-0.84).
Conclusion:
SGLT2i are associated with significantly lower major adverse cardiovascular events, heart failure hospitalizations, and all-cause mortality. The evidence is strongest in reducing heart failure hospitalizations. However, the evidence is weaker when it comes to the population subset with eGFR <60 mL/min/1.73 m2. SGLT2i are also associated with significantly lower adverse renal events, with these effects apparent even in the population with eGFR <60 mL/min/1.73 m2.
Insights
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular events, heart failure hospitalizations, and all-cause mortality. SGLT2i also demonstrate significant renal benefits, particularly in patients with reduced estimated glomerular filtration rate (eGFR).
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Previous meta-analyses showed SGLT2 inhibitors (SGLT2i) benefit patients with established atherosclerotic cardiovascular disease (ASCVD), but efficacy in at-risk populations and those with eGFR <60 mL/min/1.73 m2 remains unclear.
- A need exists to evaluate SGLT2i efficacy across a broader population, including those without established ASCVD and with impaired renal function.
- This meta-analysis assesses the combined cardiovascular and renal outcomes of SGLT2i in general and in patients with eGFR <60 mL/min/1.73 m2.
Approach:
- A systematic literature search of PubMed and Cochrane databases identified relevant randomized, placebo-controlled trials of SGLT2 inhibitors.
- Key outcomes analyzed included composite cardiovascular events (CV death, MI, stroke, HF hospitalization), renal composite outcomes, and albuminuria progression.
- Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using a fixed-effects model.
Key Points:
- SGLT2i significantly reduced major adverse cardiovascular events (RR 0.93, 95% CI 0.87-0.99) and all-cause mortality (RR 0.9, 95% CI 0.84-0.97).
- Heart failure hospitalizations showed the strongest evidence of benefit (RR 0.71, 95% CI 0.63-0.79).
- Significant renal benefits were observed, including a reduction in composite renal outcomes (RR 0.63, 95% CI 0.56-0.71) and albuminuria progression (RR 0.80, 95% CI 0.76-0.84), even in patients with eGFR <60 mL/min/1.73 m2.
Conclusions:
- SGLT2 inhibitors offer significant cardiovascular protection, particularly in reducing heart failure hospitalizations.
- Renal outcomes are consistently improved by SGLT2i, with benefits evident even in patients with moderate to severe chronic kidney disease (eGFR <60 mL/min/1.73 m2).
- While overall cardiovascular benefits are clear, the efficacy in patients with eGFR <60 mL/min/1.73 m2 warrants further investigation, though renal benefits are robust in this group.
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