Assessing 1-year sodium-glucose co-transporter-2 inhibitor tolerance in older adults.

Background: Evidence concerning tolerability of sodium-glucose co-transporter-2 (SGLT2) inhibitors in older adults is limited due to under-representation in clinical trials. Our study aimed to determine the extent to which SGLT2 inhibitor intolerance increases with age and explore additional factors associated with intolerance.

Methods: This retrospective observational study included patients in the Veterans Health Administration who initiated an SGLT2 inhibitor between 1 January 2013 and 31 December 2021. One-year discontinuation served as a proxy for intolerance. Relative risk (RR) for 1-year discontinuation was contrasted across age groups using log-binomial regression to adjust for confounding.

Results: Of 232 495 patients who initiated an SGLT2 inhibitor, 60 582 (26.1%) discontinued within one year. A difference was observed across age groups, <65, 65-74, 75-84 and ≥85 years, where 25.8%, 25.3%, 28.5% and 34.9% of patients discontinued, respectively (P < .001). After adjustment for confounding factors, patients 75-84 and ≥85 years were at 8% (RR = 1.08; 95% CI: 1.05, 1.10) and 21% increased risk (RR = 1.21; 95% CI: 1.15, 1.26) for discontinuation, respectively, relative to patients <65 years. Additional risk factors were identified: female (RR = 1.41; 95% CI: 1.37, 1.45), estimated glomerular filtration rate stage 4 (RR = 1.49; 95% CI: 1.39, 1.60), underweight (RR = 1.15; 95% CI: 1.03, 1.29), urinary tract infection history (RR = 1.25; 95% CI: 1.21, 1.30) and yeast infection history (RR = 1.39; 95% CI: 1.27, 1.51).

Conclusion: No clinically meaningful differences in SGLT2 inhibitor intolerance were observed in patients up to 84 years. Our findings support having closer follow-up when initiating in patients 85 years and older.