Mendelian randomization study of sodium–glucose cotransporter 2 inhibitors in cardiac and renal diseases

Abstract

Objective Sodium–glucose cotransporter 2 inhibitors (SGLT2i) target the reabsorption of sodium and glucose in the kidney proximal tubules to reduce blood sugar levels. However, clinical randomized controlled trials on SGLT2i have yielded inconsistent results, necessitating further research into their efficacy and safety for specific cardiac and renal diseases. Methods “Sodium in urine” was selected as a downstream biomarker of SGLT2i. Single nucleotide polymorphisms were extracted from genome-wide association study data as instrumental variables. Mendelian randomization analysis was then conducted for cardiac and renal diseases and potential adverse events. The causal effects of SGLT2i on these diseases were determined based on inverse variance weighted results, followed by sensitivity and pleiotropy tests. Results SGLT2i had a significant protective effect against nephrotic syndrome (odds ratio [OR] 0.0011, 95% confidence interval [CI] 0.000–0.237), chronic glomerulonephritis (OR 0.0002, 95% CI 0.000–0.21), and hypertensive nephropathy (OR 0.0003, 95% CI 0.000–0.785). No causal effects were observed between SGLT2i and cardiac diseases or potential adverse events. Conclusions SGLT2i can act as protective factors against nephrotic syndrome, chronic glomerulonephritis, and hypertensive nephropathy.