Comparison of risk of hyperkalemia between SGLT2 inhibitors and DPP4-inhibitors in patients with type 2 diabetes

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Hyperkalemia is a common complication and increases the risk of cardiac arrhythmias and mortality in patients with type 2 diabetes (T2DM), especially in those with diabetic nephropathy. We investigated the risk of hyperkalemia in patients initiated on SGLT2 inhibitors versus DPP-4 inhibitors among patients with T2DM. Methods This study included patients with T2DM who initiated on SGLT2 inhibitors or DPP-4 inhibitors between January 01, 2015 and December 31, 2019 from a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System [CDARS]). A multivariable cox proportional hazards analysis, adjusting for key confounders, was used to compare the risk of central laboratory-determined hyperkalemia (serum potassium ≥6.0mmol/L) and hypokalemia (serum potassium <3.5mmol/L), respectively, between SGLT2 inhibitors and DPP-4 inhibitors. Results 10193 new users of SGLT2 inhibitors were matched to 17305 new users of DPP-4 inhibitors. During the 2-year follow-up, there were 104 hyperkalemia events (incident rate [IR] = 5.17 per 1000 person-years) among SGLT2 inhibitors and 306 events (IR = 9.09 per 1000 person-years) among DPP-4 inhibitors, of which SGLT2 inhibitors were associated with a lower risk of incident hyperkalemia (Adjusted HR: 0.66 [95%CI 0.53-0.83], p<0.001), compared to DPP-4 inhibitors. The incident hypokalemia was similar between SGLT2 inhibitors and DPP-4 inhibitors (Adjusted HR: 0.91 [95%CI 0.81-1.03], P=0.13). Conclusion SGLT2 inhibitors reduced incident hyperkalemia, but without increasing incident hypokalemia compared to DPP-4 inhibitors.