Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts, USA.
J Gerontol A Biol Sci Med Sci. 2023 Dec 1;78(12):2426-2434. doi: 10.1093/gerona/glad075.
Severe hypoglycemia is associated with adverse clinical outcomes. We evaluated the risk of severe hypoglycemia in older adults initiating newer glucose-lowering medications overall and across strata of known indicators of high hypoglycemia risk.
We conducted a comparative-effectiveness cohort study of older adults aged >65 years with type 2 diabetes initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) or SGLT2i versus glucagon-like peptide-1 receptor agonists (GLP-1RA) using Medicare claims (3/2013-12/2018) and Medicare-linked-electronic health records. We identified severe hypoglycemia requiring emergency or inpatient visits using validated algorithms. After 1:1 propensity score matching, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years. Analyses were stratified by baseline insulin, sulfonylurea, cardiovascular disease (CVD), chronic kidney disease (CKD), and frailty.
Over a median follow-up of 7 (interquartile range: 4-16) months, SGLT2i was associated with a reduced risk of hypoglycemia versus DPP-4i (HR 0.75 [0.68, 0.83]; RD -3.21 [-4.29, -2.12]), and versus GLP-1RA (HR 0.90 [0.82, 0.98]; RD -1.33 [-2.44, -0.23]). RD for SGLT2i versus DPP-4i was larger in patients using baseline insulin than in those not, although HRs were similar. In patients using baseline sulfonylurea, the risk of hypoglycemia was lower in SGLT2i versus DPP-4i (HR 0.57 [0.49, 0.65], RD -6.80 [-8.43, -5.16]), while the association was near-null in those without baseline sulfonylurea. Results stratified by baseline CVD, CKD and frailty were similar to the overall cohort findings. Findings for the GLP-1RA comparison were similar.
SGLT2i was associated with a lower hypoglycemia risk versus incretin-based medications, with larger associations in patients using baseline insulin or sulfonylurea.
严重低血糖与不良临床结局相关。我们评估了新的降糖药物在总体和已知低血糖高风险指标分层中对老年患者发生严重低血糖的风险。
我们使用医疗保险索赔数据（2013 年 3 月至 2018 年 12 月）和医疗保险相关电子健康记录，对年龄＞65 岁、患有 2 型糖尿病且开始使用钠-葡萄糖协同转运蛋白 2 抑制剂（SGLT2i）的患者进行了一项比较有效性队列研究，比较了 SGLT2i 与二肽基肽酶-4 抑制剂（DPP-4i）或 SGLT2i 与胰高血糖素样肽-1 受体激动剂（GLP-1RA）的效果。我们使用验证后的算法确定需要急诊或住院治疗的严重低血糖事件。经过 1:1 倾向评分匹配后，我们估计了每 1000 人年的危险比（HR）和率差异（RD）。分析按照基线时是否使用胰岛素、磺酰脲类药物、心血管疾病（CVD）、慢性肾脏病（CKD）和虚弱情况进行分层。
在中位随访 7 个月（四分位间距：4-16 个月）期间，与 DPP-4i 相比，SGLT2i 降低低血糖风险（HR 0.75 [0.68, 0.83]; RD -3.21 [-4.29, -2.12]），与 GLP-1RA 相比（HR 0.90 [0.82, 0.98]; RD -1.33 [-2.44, -0.23]）。与基线时使用胰岛素的患者相比，SGLT2i 与 DPP-4i 相比 RD 更大，而 HR 相似。在基线时使用磺酰脲类药物的患者中，SGLT2i 与 DPP-4i 相比低血糖风险更低（HR 0.57 [0.49, 0.65], RD -6.80 [-8.43, -5.16]），而在基线时未使用磺酰脲类药物的患者中，二者关联接近零。按基线 CVD、CKD 和虚弱情况分层的结果与总体队列的发现相似。GLP-1RA 比较的结果也相似。
与基于肠促胰岛素的药物相比，SGLT2i 与低血糖风险降低相关，在基线时使用胰岛素或磺酰脲类药物的患者中，相关性更大。
