Risk of hyperkalaemia in patients with type 2 diabetes mellitus prescribed with SGLT2 versus DPP-4 inhibitors

Abstract Aims To investigate the risk of hyperkalaemia in new users of sodium–glucose cotransporter 2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes mellitus (T2DM). Methods and results Patients with T2DM who commenced treatment with an SGLT2 or a DPP-4 inhibitor between 2015 and 2019 were collected. A multivariable Cox proportional hazards analysis was applied to compare the risk of central laboratory-determined severe hyperkalaemia, hyperkalaemia, hypokalaemia (serum potassium ≥6.0, ≥5.5, and <3.5 mmol/L, respectively), and initiation of a potassium binder in patients newly prescribed an SGLT2 or a DPP-4 inhibitor. A total of 28 599 patients (mean age 60 ± 11 years, 60.9% male) were included after 1:2 propensity score matching, of whom 10 586 were new users of SGLT2 inhibitors and 18 013 of DPP-4 inhibitors. During a 2-year follow-up, severe hyperkalaemia developed in 122 SGLT2 inhibitor users and 325 DPP-4 inhibitor users. Use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalaemia [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58–0.88] compared with DPP-4 inhibitors. Risk of hyperkalaemia (HR 0.81, 95% CI 0.71–0.92) and prescription of a potassium binder (HR 0.74, 95% CI 0.67–0.82) were likewise decreased with SGLT2 inhibitors compared with DPP-4 inhibitors. Occurrence of incident hypokalaemia was nonetheless similar between those prescribed an SGLT2 inhibitor and those prescribed a DPP-4 inhibitor (HR 0.90, 95% CI 0.81–1.01). Conclusion Our study provides real-world evidence that compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with lower risk of hyperkalaemia and did not increase the incidence of hypokalaemia in patients with T2DM.