Starting sodium-glucose cotransporter 2 inhibitors in older adults who are already taking renin-angiotensin-aldosterone system inhibitors was linked to fewer cases of hyperkalemia and less treatment interruption, according to a large real-world study.
The study included over 39,000 adults aged 66 and older with diabetes, heart failure, or chronic kidney disease. All participants were prescribed renin-angiotensin-aldosterone system (RAAS) inhibitors, and the investigators followed them for up to 1 year to assess the impact of adding a sodium-glucose cotransporter 2 (SGLT2) inhibitor on potassium levels. Hyperkalemia, or elevated blood potassium, is a known side effect of RAAS therapy and often leads to dose reduction or discontinuation.
Among the study population, 20,063 participants started an SGLT2 inhibitor—most commonly empagliflozin, canagliflozin, or dapagliflozin—while 19,781 participants who did not start the therapy served as a comparison group.
Patients who began SGLT2i treatment had a lower incidence of hyperkalemia: 79 events per 1,000 person-years, compared with 90 per 1,000 person-years in nonusers. The hazard ratio (HR) was 0.89 (95% confidence interval [CI] = 0.82–0.96), which indicated a statistically significant difference.
Hospital encounters for hyperkalemia were also less common among SGLT2i users (HR = 0.61, 95% CI = 0.52–0.71). Rates of severe hyperkalemia, defined as potassium levels above 6.5 mEq/L, did not differ significantly between groups (HR = 0.75, 95% CI = 0.53–1.06).
The researchers also found that SGLT2i users were more likely to continue their RAAS therapy. Discontinuation occurred in 36% of SGLT2i users vs 45% of nonusers (P < .001). Among those who stopped RAASi, 7.6% had an elevated potassium level above 5 mEq/L beforehand.
The investigators also analyzed results by kidney function, albuminuria, potassium levels at baseline, and other clinical factors. The association between SGLT2i use and reduced hyperkalemia risk remained consistent across most subgroups. The effect was more noticeable in those with lower baseline potassium (4.5–5.0 mEq/L) compared with those who had slightly higher levels at baseline (5.1–5.5 mEq/L).
To reduce bias, the researchers used inverse probability of treatment weighting to balance characteristics between groups. All participants had at least one potassium test within the year before follow-up.
Overall, 95% of SGLT2i users had diabetes, 17% had heart failure, and 32% had moderate to severe chronic kidney disease. The majority received standard doses of SGLT2 inhibitors. Empagliflozin was the most commonly prescribed.
“In addition to the protective effects of these agents on kidney and cardiovascular health, the introduction of SGLT2 inhibitors may help overcome a key obstacle to implementing optimal guideline-directed medical therapy in patients with diabetes, CKD, and heart failure,” concluded study author Sara Wing, MDCM, of St. Michael’s Hospital and the University of Toronto.
Full author disclosures are available in the original publication.
Source: JAMA Internal Medicine
