Hyperkalemia may be less common with GLP-1s than DPP-4s
Patients with type 2 diabetes who were taking glucagon-like peptide-1 (GLP-1) receptor agonists had lower rates of hyperkalemia than those taking dipeptidyl peptidase-4 (DPP-4) inhibitors and were more likely to continue renin-angiotensin system inhibitors over the long term, a cohort study found.
Glucagon-like peptide-1 (GLP-1) receptor agonists were associated with less hyperkalemia and more long-term use of renin-angiotensin system (RAS) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors in a recent study.
Researchers in Sweden performed a cohort study of adults with type 2 diabetes who had started treatment with GLP-1 receptor agonists or DPP-4 inhibitors between Jan. 1, 2008, and Dec. 31, 2021. The primary outcome was time to any hyperkalemia, defined as a potassium level above 5.0 mEq/L, and moderate to severe hyperkalemia, defined as a potassium level above 5.5 mEq/L. Time to discontinuation of RAS inhibitors among patients using them at baseline was also examined. The results were published Aug. 12 by JAMA Internal Medicine.
Overall, 33,280 patients, 13,633 who started GLP-1 receptor agonists and 19,647 who started DPP-4 inhibitors, were included in the study. Mean age was 63.7 years, and 59.7% were men. Use of GLP-1 receptor agonists was associated with lower rates of any hyperkalemia or moderate to severe hyperkalemia compared with DPP-4 inhibitor use (hazard ratios [HRs], 0.61 [95% CI, 0.50 to 0.76] and 0.52 [95% CI, 0.28 to 0.84], respectively). At baseline, 21,751 patients were taking RAS inhibitors. Over a median follow-up of 3.9 months (interquartile range, 1.0 to 10.9 months), 2,351 stopped the drugs, with discontinuation less likely in the GLP-1 receptor agonist group versus the DPP-4 inhibitor group (HR, 0.89; 95% CI, 0.82 to 0.97). The authors found consistent results in intention-to-treat analyses and across subgroups of age, sex, cardiovascular comorbidity, and baseline kidney function.
The study lacked information on potential confounders as well as race and ethnicity, among other limitations, the authors noted. They concluded that in routine care of adults with type 2 diabetes, GLP-1 receptor agonists were associated with less hyperkalemia and longer RAS inhibitor use than DPP-4 inhibitors. “Treatment with GLP-1 [receptor agonists] may enable wider use of the guideline-recommended cardioprotective and renoprotective medications and contribute to improving clinical outcomes in this population,” they wrote.