#1704 GLP-1RA versus DPP-4 inhibitors and rates of hyperkalemia and discontinuation of renin-angiotensin system (RAS) blockade in Swedish routine care

Abstract

Abstract Background and Aims Emerging evidence suggest that glucagon-like peptide-1 receptor agonists (GLP-1RA) influence tubular handling of electrolytes and increase potassium excretion, which may translate into reduced risk of hyperkalemia. Hyperkalemia is a common complication that limits persistence on guideline-recommended RAS inhibitors (RASi). Here, we quantified and compared rates of hyperkalemia and RASi discontinuation among users of GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in a large healthcare system. Method We used data from the SCREAM project (Jan 2008-Dec 2021) to conduct a population-based active-comparator, new-user cohort study of adults with type-2 diabetes who started GLP-1RA or DPP-4i. The primary outcome was hyperkalemia occurrence, overall (plasma potassium>5.0 mmol/L) and by severity (mild -potassium >5-≤5.5 mmol/L- and moderate-severe -potassium >5.5 mmol/L- hyperkalemia). Among ongoing RASi users, we assessed time to RASi discontinuation through evaluation of subsequent RASi dispensations. Cox regression with inverse probability of treatment weighting (IPTW) was used to estimate pooled hazard ratios (HRs) and rate differences. Major cardiovascular events (MACEs) served as positive control outcome to evaluate unmeasured confounding bias. Results During a median follow-up of 3.0 (Interquartile range [IQR] 1.2-5.6) years, we identified 33 280 eligible participants, of which 13 633 started GLP-1RA and 19 647 DPP-4i. Mean age was 64 years and 40% were women. Compared with DPP-4i, starting GLP-1RA was associated with a lower rate of hyperkalemia (Hazard ratio [HR] 0.91; 95% CI: 0.84-0.99, Fig. 1), with no suggestion of effect modification by baseline eGFR strata (HR 0.91 (0.78-1.07) for eGFR ≥60 and HR 0.92 (0.83-1.01) for eGFR <60 ml/min/1.73 m2, P for interaction >0.05). Similar findings were observed for mild (HR 0.90; 0.83-0.98) and moderate-severe (HR 0.92; 0.80-1.06) hyperkalemia. Out of 21 751 participants that were using RASi, 8 463 discontinued this therapy during median 2.0 (0.7, 4.1) years of follow-up. Initiation of GLP-1RA vs. DPP-4i was associated with lower rate of RASi discontinuation (HR: 0.93; 0.87-0.98), with no interaction across strata of baseline eGFR (HR 0.97 (0.83-1.12) for eGFR ≥60 and HR 0.93 (0.87-0.99) for <60 ml/min/1.73 m2, P for interaction >0.05). Consistent with trial evidence, we observed a lower rate of MACE for GLP-1RA vs DPP-4i (HR 0.87; 0.78-0.98). Conclusion In patients with diabetes managed in routine care, the use of GLP-1RA was associated with lower rates of hyperkalemia and discontinuation of RASi compared with DPP-4i, providing further observational evidence in support of the use of these medications.