Sodium-glucose Cotransporter-2 Inhibitors in Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with Type 2 Diabetes Mellitus: A Meta-analysis

ABSTRACT

Background: The available evidence was systematically reviewed to evaluate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) on cardiovascular (CV) and renal outcomes in people with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors (MRF), with or without heart failure (HF), and per estimated glomerular filtration rate (eGFR) rate at baseline. Methods: We comprehensively searched three electronic databases to retrieve publications up to 30th November 2019, which were screened for inclusion. The data extracted for the outcomes according to baseline ASCVD, HF, and eGFR levels were meta-analyzed using fixed effects model. Results: Of the 735 screened citations, 15 primary and secondary publications from five CV or renal outcome trials were included. SGLT2is reduced the risk of CV death or hospitalization for HF (HHF), HHF alone, and composite renal-specific outcome, irrespective of ASCVD and HF at baseline. The three-point major adverse cardiovascular events (3P-MACE) risk was reduced by 14% (p<0.001) in patients with ASCVD and by 10% (p = 0.018) in those without baseline HF compared with their counterparts. SGLT2is significantly reduced the risk of MACE (18%) in patients with mild kidney dysfunction (eGFR within the range of 60–<90 mL/min/1.73 m2 and <60 mL/min/1.73 m2 ). Conclusion: SGLT2is are effective for both secondary and primary prevention of composite CV outcomes, and secondary prevention of MACE. The upcoming evidence may strengthen the primary prevention benefits of SGLT2is.