Association between sodium-glucose cotransporter-2 inhibitor and adverse events in patients with moderate to severe chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.

Purpose: Although there is concern about the association of sodium-glucose cotransporter-2 inhibitor (SGLT2i) use with musculoskeletal pain, hypovolemia, and urinary tract infection in patients with severe chronic kidney disease (CKD), information on these adverse events is insufficient. The aim of this systematic review and meta-analysis was to assess whether SGLT2i increases the risk of urinary tract infection, hypovolemia, and musculoskeletal pain in these patients.

Methods: MEDLINE via PubMed, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov website were comprehensively searched to extract all relevant studies. Randomized controlled trials (RCTs) were selected that compared SGLT2i versus placebo, and the study populations consisted of patients with CKD stage 3 or higher.

Results: Eleven studies were eligible for inclusion. SGLT2i tended to increase the risk of hypovolemia [risk ratio (RR) 1.15, 95% confidence interval (CI) 0.98-1.35, P = 0.08, high certainty] but did not increase the risk of urinary tract infection (RR 1.03, 95% CI 0.94-1.12, P = 0.56, high certainty) or musculoskeletal pain (RR 0.69, 95% CI 0.41-1.17, P = 0.17, high certainty). Subgroup analysis of patients with heart disease was performed for the outcome of hypovolemia, and the results showed a significant difference in hypovolemia (RR 1.21, 95% CI 1.06-1.39, P < 0.01, moderate certainty) between SGLT2i and placebo.

Conclusion: This meta-analysis suggests that SGLT2i may increase the risk of hypovolemia in patients with moderate to severe CKD and heart disease but is not associated with urinary tract infection or musculoskeletal pain.