#762 Hyperkalemia and discontinuation of RAS blockade after initiating SGLT-2i vs. DPP-4i in patients with type 2 diabetes; a population-based cohort study

Abstract

Abstract Rate of hyperkalemia and discontinuation of renin-angiotensin system blockade after initiating SGLT-2 inhibitors vs. DPP-4 inhibitors in patients with type 2 diabetes; a population-based cohort study Background and Aims Post-hoc analyses of clinical trials have suggested that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) lower the rate of hyperkalemia and facilitate the use of renin-angiotensin system inhibitors (RASi) in people with type 2 diabetes and CKD. Whether these effects are generalizable to patients treated in routine clinical practice is unclear. Here, we evaluated the comparative effects of SGLT-2i and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the rate of hyperkalemia and RASi discontinuation. Method We conducted a population-based active-comparator, new-user cohort study using data from the Stockholm CREAtinine Measurements (SCREAM) project of people with type 2 diabetes who newly initiated SGLT-2i or DPP-4i between January 2014 and December 2021. The primary outcomes were time to first outpatient hyperkalemia (plasma potassium >5.0 mmol/L) occurrence and recurrent hyperkalemia. The secondary outcomes were mild (potassium >5-≤5.5 mmol/L) and moderate-severe (potassium >5.5 mmol/L) hyperkalemias. Among RASi users, we also studied time to RASi discontinuation through evaluation of pharmacy fills. Cox regression with inverse probability of treatment weighting was used to estimate hazard ratios (HRs) and rate differences for time to first hyperkalemia. Weighted Poisson regression was used to estimate incidence rate ratios (IRRs) for hyperkalemia recurrence. Results We included 24 417 individuals (of which 14 470 initiated SGLT-2i and 9, 947 DPP-4i therapy), followed for median 2.0 (Q1-Q3 0.8-3.7) years. Mean age was 67 years and 37% were women. Compared with DPP-4i, initiation of SGLT-2i was associated with a lower rate of first hyperkalemia (adjusted hazard ratio [HR] 0.83; 95% CI 0.72-0.96) and recurrent hyperkalemia (incidence rate ratio [IRR] 0.75; 0.64-0.85). Similar findings were observed among people with eGFR ≥60 (HR 0.73; 95% CI 0.63-0.86) and <60 (HR 0.87; 95% CI 0.63-1.16) ml/min/1.73 m2, as well as for mild (HR 0.82; 95% CI 0.71-0.95) and moderate-severe (HR 0.67; 95% CI 0.52-0.84) hyperkalemias. Out of 15 746 participants that were prevalent RASi users, 17% discontinued RASi therapy during 2.0 (IQR 0.8-3.7) years of follow-up. Initiation of SGLT-2i vs. DPP-4i was not associated with the rate of RASi discontinuation (HR: 1.00; 0.91-1.11). Conclusion In patients with type 2 diabetes managed in routine clinical care, the use of SGLT-2i was associated with a lower rate of first and recurrent hyperkalemia compared with DPP-4i. However, this was not accompanied by higher persistence on RASi therapy.