SGLT-2s, GLP-1s linked with lower hyperkalemia rate than DPP-4s
Initiating therapy with sodium-glucose cotransporter-2 (SGLT-2) inhibitors was associated with the lowest risk of hyperkalemia in a retrospective comparison with glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors.
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists were associated with a lower risk of hyperkalemia than dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes, a population-based study found.
Investigators assessed claims data from Medicare and two commercial databases from April 2013 to April 2022 to evaluate the effectiveness of the three drug classes in preventing hyperkalemia in routine clinical practice. Researchers matched adults with type 2 diabetes who initiated SGLT-2 inhibitors versus DPP-4 inhibitors (n=778,908), GLP-1 receptor agonists versus DPP-4 inhibitors (n=729,820), and SGLT-2 inhibitors versus GLP-1 receptor agonists (n=873,460). Average on-treatment follow-up was between 8.1 and 8.8 months. Findings were published by The BMJ on June 26.
Starting treatment with an SGLT-2 inhibitor was linked with a lower rate of hyperkalemia compared to DPP-4 inhibitors (hazard ratio [HR], 0.75; 95% CI, 0.73 to 0.78) and compared to GLP-1 receptor agonists (HR, 0.92; 95% CI, 0.89 to 0.95). GLP-1 receptor agonists were associated with a lower hyperkalemia rate than DPP-4 inhibitors (HR, 0.79; 95% CI, 0.77 to 0.82). Compared with DPP-4 inhibitors, the three-year absolute risk of hyperkalemia was 2.4% (95% CI, 2.1% to 2.7%) lower in patients initiating SGLT-2 inhibitors and 1.8% (95% CI, 1.4% to 2.1%) lower with GLP-1 receptor agonists.
Findings were consistent regardless of age, sex, race, and HbA1c level. The benefits of initiating SGLT-2 inhibitors and GLP-1 receptor agonists on hyperkalemia were largest among patients who had heart failure or chronic kidney disease or took mineralocorticoid receptor antagonists. Lower hyperkalemia rates were consistent across individual medications in SGLT-2 inhibitor and GLP-1 receptor agonist drug classes.
One reason SGLT-2 inhibitors and GLP-1 receptor agonists may lower the risk of hyperkalemia is because they slow the progression of kidney decline and albuminuria, the researchers explained. This preserved function may contribute to the long-term prevention of hyperkalemia.
Overall, "The consistency of associations among individual agents in the SGLT-2 inhibitor and GLP-1 receptor agonist classes suggests a class effect. These ancillary benefits of SGLT-2 inhibitors and GLP-1 receptor agonists further support their use in people with type 2 diabetes, especially in those at risk of hyperkalemia," the study authors concluded.