SGLT-2 inhibitors and cardiovascular outcomes in patients with and without a history of heart failure: a systematic review and meta-analysis

Abstract

Aims Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have cardiovascular (CV) benefits in patients with heart failure with reduced ejection fraction (HFrEF). Whether these medications improve CV outcomes irrespective of heart failure history or left ventricular ejection fraction (LVEF) in HFrEF remains unknown. Methods and Results All randomized, placebo-controlled trials of SGLT-2 inhibitors reporting similar CV outcomes were searched in PubMed from January 1, 2010 to October 1, 2021. The primary outcome was the composite of hospitalization for heart failure or CV death. Secondary outcomes included all-cause mortality. Pooled hazard ratios (HR) and 95% confidence intervals (CI) were used as effect estimates and calculated with a random-effects model. Data from eleven trials and a total of 66,957 patients (n = 36,758 SGLT-2 group, n = 30,199 placebo group) were included. SGLT-2 inhibitors reduced the risk of hospitalization for heart failure or CV death in patients with (HR 0.76 95% CI 0.71–0.80) and without (HR 0.76 95% CI 0.68–0.86; pinteraction = 0.69) heart failure. Patients with (HR 0.87 95% CI 0.80–0.95) and without (HR 0.84 95% CI 0.73–0.95; pinteraction = 0.67) heart failure treated with SGLT-2 inhibitors had a reduction in all-cause mortality. Reduction in the primary outcome was consistently observed in HFrEF patients with (HR 0.68 95% CI 0.59–0.78) and without (HR 0.84 95% CI 0.71–0.99; pinteraction = 0.13) severely reduced LVEF, and in heart failure with preserved ejection fraction patients (HR 0.80 95% CI 0.70–0.92; pinteraction = 0.65). Conclusion SGLT-2 inhibitors improved CV outcomes irrespective of heart failure history or type, and severity of LVEF reduction. PROSPERO registration: https://www.crd.york.ac.uk/prospero/CRD42020219082.

All‐cause mortality and cardiovascular outcomes with sodium‐glucose Co‐transporter 2 inhibitors, glucagon‐like peptide‐1 receptor agonists and with combination therapy in people with type 2 diabetes

“…Finally, SGLT2i have also showed a marked reduction in the progression in CKD in patients with or without type 2 diabetes (CREDANCE with canagliflozin, 22 DAPA‐CKD with dapagliflozin 10 and SCORED with sotagliflozin 23 and EMPA‐KIDNEY with empagliflozin 24 ). These landmark RCTs showed the pleiotropic benefits of SGLT2i 25 resulting in licensing authorizations in those with type 2 diabetes, heart failure with reduced ejection fraction and CKD. The results of our study further support the ubiquitous mortality and cardiovascular benefits of SGLT2i therapy in people with type 2 diabetes through showing these effects in the real world.…”

Insulin Therapy is Associated With Increased Myocardial Interstitial Fibrosis and Cardiomyocyte Apoptosis in a Rodent Model of Experimental Diabetes

“…In fact, several GLP-1 agonists have already been shown to reduce adverse cardiovascular outcomes among diabetics ( Sheahan et al, 2020 ). SGLT2i, such as Empagliflozin ( Anker et al, 2021 ) and Dapagliflozin ( McMurray et al, 2019 ), bestow favorable cardiovascular effects, regardless of the patients’ diabetic status ( McMurray et al, 2019 ; Anker et al, 2021 ; Razuk, 2022 ).…”

The Roles of Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists and Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors in Decreasing the Occurrence of Adverse Cardiorenal Events in Patients With Type 2 Diabetes

“…Studies have shown that SGLT-2i have been approved for heart failure patients with reduced ejection fraction (HFrEF) even if they do not have diabetes [ 30 ]. Perhaps one of the most important benefits of using SGLT-2i is its cardiac benefits, including the reduction of major cardiovascular events, hospitalization rates due to heart failure, and death.…”