The Effects of Sodium-Glucose Cotransporter-2 Inhibitors (SLGT-2i) on Cardiovascular and Renal Outcomes in Non-diabetic Patients: A Systematic Review

Abstract

Globally, cardiovascular disease (CVD) and chronic kidney disease (CKD) are the leading causes of mortality. Despite medical advances, these illnesses are still underdiagnosed and undermanaged. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have recently emerged as a potential class of medications with promising cardiovascular and renal safety in non-diabetic patients. In this systematic review, we explored the outcomes of cardiovascular and renal protective effects utilizing SGLT-2i in three large randomized clinical trials with a cohort of both diabetes and non-diabetes patients. In these studies, data conferred that there is a significant reduction in heart failure (HF) hospitalization, as well as cardiovascular and all-cause mortality. Moreover, SGLT-2i impede the progression to and death from CKD. Additionally, we reviewed trials solely done on non-diabetics which demonstrated benefits in patients with established HF with reduced ejection fraction, though the fact that these studies had a smaller sample size. We also discussed some of the potential mechanisms of action of SGLT-2i on cardiovascular and renal outcomes that are beyond anti-hyperglycemic control. There is ongoing research involving a larger number of non-diabetes patients that may provide more information about the efficacy of these drugs besides anti-diabetic medications in the future. Finally, this is the first systematic review that has provided a perspective on the currently available trials, which offer evidence supporting the potential benefits of SGLT-2i on cardiovascular and renal outcomes in non-diabetic individuals.

Cost-effectiveness of screening for chronic kidney disease using a cumulative eGFR-based statistic

“…When combined with ACE/ARBs inhibitors, these agents have shown a capacity to reduce cardiovascular mortality and heart failure events [ 43 , 44 ]. Additionally, they have demonstrated a potential in slowing the progression of kidney dysfunction in patients, irrespective of their diabetic status [ 45 , 46 ]. Given the limited data on SGLT2 inhibitors cost-effectiveness in CKD management and limited incorporation into standard care practices, we adopted a conservative approach in assuming that the efficacy of SGLT2 inhibitors on kidney function is comparable between patients with and without diabetes.…”

Guía mexicana de práctica clínica para el diagnóstico y el tratamiento de la insuficiencia cardiaca

“…Una RS publicada en 2022 por Ravindran et al 148 tuvo como objetivo evaluar el beneficio de los iSGLT-2 en pacientes con ERC e insuficiencia cardiaca, en pacientes con diabetes y sin diabetes. Los autores evaluaron los efectos protectores cardiovasculares y renales con los SGLT-2i en tres grandes ECAs con una cohorte de pacientes con y sin diabetes.…”

“…Los resultados concluyen que existe una reducción significativa de las hospitalizaciones por insuficiencia cardíaca y de muerte cardiovascular y por todas las causas. Además, los iSGLT-2 impiden la progresión y la muerte por ERC 148 . Una RS publicada por Spanella et al 149 en 2020 tuvo como objetivo evaluar el impacto de sacubitrilo/valsartán en la progresión de la ERC.…”

Relationship between sodium–glucose cotransporter-2 inhibitors and muscle atrophy in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

“…The pathophysiology of the cardioprotective outcome produced by the application of SGLT-2i is not known. Possible mechanisms of action include its role in anti-inflammatory and oxidative stress pathways ( 10 ). A recent review summarized animal studies and clinical trials of SGLT-2i analogs, which showed that they have pharmacological effects in the treatment of diabetes by attenuating oxidative stress associated with T2DM, which may explain their cardiovascular benefits and have promising applications in the treatment of T2DM ( 11 ).…”