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.

中文翻译：

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评估老年人 1 年钠-葡萄糖协同转运蛋白 2 抑制剂耐受性


背景 由于临床试验中的代表性不足，关于钠-葡萄糖协同转运蛋白-2 （SGLT2） 抑制剂在老年人中耐受性的证据有限。我们的研究旨在确定 SGLT2 抑制剂不耐受随年龄增长而增加的程度，并探讨与不耐受相关的其他因素。方法 这项回顾性观察性研究包括 2013 年 1 月 1 日至 2021 年 12 月 31 日期间开始使用 SGLT2 抑制剂的退伍军人健康管理局患者。停药一年是不耐受的代表。使用对数二项式回归对各年龄组停药 1 年的相对风险 （RR） 进行对比，以调整混杂因素。结果 在 232 495 例开始使用 SGLT2 抑制剂的患者中，60 582 例 （26.1%） 在 1 年内停药。在年龄组之间观察到差异，<65、65-74、75-84 和 ≥85 岁，其中 25.8%、25.3%、28.5% 和 34.9% 的患者停药 （P < .001）。在调整混杂因素后，75-84 岁和 ≥85 岁患者相对于患者 <65 岁，停药风险分别增加 8% （RR = 1.08;95% CI： 1.05， 1.10） 和 21% （RR = 1.21;95% CI： 1.15， 1.26）。确定了其他危险因素：女性 （RR = 1.41;95% CI： 1.37， 1.45）、估计肾小球滤过率 4 期 （RR = 1.49;95% CI： 1.39， 1.60）、体重不足 （RR = 1.15;95% CI： 1.03， 1.29）、尿路感染史 （RR = 1.25;95% CI： 1.21， 1.30） 和酵母菌感染史 （RR = 1.39;95% CI： 1.27， 1.51）。结论 在 84 岁以下的患者中未观察到 SGLT2 抑制剂不耐受的临床意义差异。我们的研究结果支持在 85 岁及以上的患者中开始时进行更密切的随访。