A Systematic Review of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and Sympathetic Nervous System Inhibition: An Underrated Mechanism of Cardiorenal Protection

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have many actions beyond glycemic control. The drug leads to favorable cardiovascular and renal outcomes. In this review, we focused on how SGLT2 inhibitors produce these outcomes and what role it plays in the inhibition of the sympathetic nervous system in diabetic patients. We searched PubMed, Google Scholar, and Biomed Central databases from January 2016 to February 2022. The authors used specific keywords and the Medical Subject Heading (MeSH) strategy. We identified a total of 3,961 records. Strict inclusion-exclusion criteria were followed to gather relevant data. From 3,961 results found through electronic databases, we finally selected 161 studies after the removal of duplicates, excluding irrelevant studies and those that did not fall into inclusion criteria. Forty-one studies underwent an extensive content search and quality appraisal using specific tools. It included a total of 12 best studies to conduct the systematic review supporting data from 17 other studies. Our review found that the SGLT2 inhibitors significantly reduced cardiovascular endpoints, including cardiovascular death, heart failure hospitalization, and all-cause mortality, with varying effects on major adverse cardiovascular (MACE). There were nominal improvements in renal outcomes (decline in renal disease progression, decreased albuminuria, less need for renal replacement therapy [RRT], and stable estimated glomerular filtration rate [eGFR]). Inhibition of the sympathetic nervous system (SNS) is an important and under-studied mechanism of SGLT2 inhibitors. This systematic review explores that SGLT2 inhibitors decrease the time to first cardiovascular event or death, less heart failure hospitalizations (HFH), and reduced MACE. Improvements in renal function preserved eGFR and reduction in RRT. Also, this drug inhibits SNS further by aiding in cardiorenal protection.