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. 2025 Jun 30:19:11795468251347777.
doi: 10.1177/11795468251347777. eCollection 2025.

Evaluating the Safety and Efficacy of SGLT-2 Inhibitors on Reducing Cardiovascular and Renal Mortality, Morbidity and Inflammatory Outcomes in Various Patient Populations: A Systematic Review and Meta-Analysis of 92 920 Patients

Syed Hamza Haider  1 , Areeka Irfan  1 , Samir Mustafa Sheikh  1 , Muhammad Omar Larik  2 , Alishba Raza  1 , Yumna Khabir  1
Affiliations

Evaluating the Safety and Efficacy of SGLT-2 Inhibitors on Reducing Cardiovascular and Renal Mortality, Morbidity and Inflammatory Outcomes in Various Patient Populations: A Systematic Review and Meta-Analysis of 92 920 Patients

Syed Hamza Haider et al. Clin Med Insights Cardiol. .

Abstract

Background: The effect of Sodium Glucose Co-Transporter 2 inhibitors on cardiovascular, renal, dyslipidemia, and inflammatory markers has not been analyzed simultaneously. The goal is to determine if SGLT2 inhibitors significantly reduce cardiovascular and renal mortality, and improve these health outcomes.

Methods: PubMed, Cochrane Library and MEDLINE databases were used to conduct a comprehensive literature search from inception to September 2023. Randomized control trials with follow-up for at least 8 weeks, with a group taking SGLT2 inhibitors being compared with a group taking either placebo or other medication, in which cardiovascular outcomes, renal outcomes, lipid biomarkers, and inflammatory markers were reported as the primary outcomes were included. The statistical analyses were conducted using Review Manager with a random-effects model.

Results: Thirteen studies comprising 92 920 patients were analyzed for several outcomes. The analysis revealed a significant reduction in overall mortality, death due to heart failure, cardiovascular causes, and renal causes in the SGLT2 inhibitor group as compared to placebo. Pooled results also revealed a significant reduction in the frequency of renal replacement therapy and renal composite endpoint in patients on SGLT2 inhibitors. There was also a significant reduction in IL-6, TNF-a, systolic blood pressure in the same group. On the other hand, Flow Mediated Dilation (FMD), lipid profile, and the incidence of amputations and fractures showed no significant associated SGLT2 inhibitor therapy.

Conclusion: Our analysis indicates that diabetics and non-diabetics suffering from cardiovascular and renal diseases experience a significant reduction in morbidity and mortality from SGLT2 inhibitor therapy, leading to a better prognosis of such conditions in the long-term.

Keywords: SGLT2 inhibitor; cardiology; cardiovascular; endothelial dysfunction; heart failure; meta analysis; pharmacology.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Forest plot of systolic BP: (MD: −1.41; 95% CI [−2.53 to −0.30]; P = .01).
Figure 2.
Figure 2.
(A) Forest plot of renal composite: (RR: 0.65; 95% CI [0.54-0.78]; P < .00001; I2 = 59%) and (B) post sensitivity forest plot of renal composite: (RR: 0.58; 95% CI [0.52-0.66]; P < .00001; I2 = 0%).
Figure 3.
Figure 3.
Forest plot of renal replacement therapy: (RR: 0.72; 95% CI [0.59-0.88]; P = .002).
Figure 4.
Figure 4.
Forest plot of hospitalization for HF: (RR: 0.71; 95% CI [0.67-0.75]; P < .00001).
Figure 5.
Figure 5.
Forest plot of death from heart failure: (RR: 0.80; 95% CI [0.76-0.86]; P < .00001).
Figure 6.
Figure 6.
Forest plot of death from renal causes: (RR: 0.27; 95% CI [0.11-0.68]; P = .005).
Figure 7.
Figure 7.
Forest plot of death from CVS causes: (RR: 0.88; 95% CI [0.81-0.95]; P = .0007).
Figure 8.
Figure 8.
Forest plot of death from any cause: (RR: 0.89; 95% CI [0.84-0.95]; P = .0006).
Figure 9.
Figure 9.
(A) Forest plot of FMD: (MD: 1.25; 95% CI [−0.57 to 3.08]; P = .18; I2 = 73%) and (B) post sensitivity forest plot of FMD: (MD: 0.40; 95% CI [−0.41 to 1.21]; P = .33; I2 = 0%).
Figure 10.
Figure 10.
(A) Forest plot of total cholesterol levels: (MD: −0.80; 95% CI [−11.07 to 9.47]; P = .88; I2 = 78%) and (B) post sensitivity forest plot of total cholesterol levels: (MD: 3.11; 95% CI [−4.59 to 10.82]; P = .43; I2 = 39%).
Figure 11.
Figure 11.
Forest plot of triglycerides: (MD: −5.43; 95% CI [−17.06 to 6.19]; P = .36).
Figure 12.
Figure 12.
Forest plot of LDL: (MD: 2.05; 95% CI [−2.33 to 6.43]; P = .36).
Figure 13.
Figure 13.
Forest plot of TNF-a: (MD: −0.20; 95% CI [−0.28 to −0.12]; P ⩽ .00001).
Figure 14.
Figure 14.
Forest plot of IL-6: (MD: −0.2; 95% CI [−0.27 to −0.12]; P ⩽ .00001).
Figure 15.
Figure 15.
Forest plot of fractures: (RR: 1.04; 95% CI [0.95 to 1.15]; P = .38).
Figure 16.
Figure 16.
Forest plot of amputations: (RR: 1.06; 95% CI [0.91 to 1.22]; P = .46).
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