Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK.
Division of Molecular & Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
Diabetologia. 2024 Sep;67(9):1817-1827. doi: 10.1007/s00125-024-06190-9. Epub 2024 Jun 5.
AIMS/HYPOTHESIS: Older adults are under-represented in trials, meaning the benefits and risks of glucose-lowering agents in this age group are unclear. The aim of this study was to assess the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in people with type 2 diabetes aged over 70 years using causal analysis.
Hospital-linked UK primary care data (Clinical Practice Research Datalink, 2013-2020) were used to compare adverse events and effectiveness in individuals initiating SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Analysis was age-stratified: <70 years (SGLT2i n=66,810, DPP4i n=76,172), ≥70 years (SGLT2i n=10,419, DPP4i n=33,434). Outcomes were assessed using the instrumental variable causal inference method and prescriber preference as the instrument.
Risk of diabetic ketoacidosis was increased with SGLT2i in those aged ≥70 (incidence rate ratio compared with DPP4i: 3.82 [95% CI 1.12, 13.03]), but not in those aged <70 (1.12 [0.41, 3.04]). However, incidence rates with SGLT2i in those ≥70 was low (29.6 [29.5, 29.7]) per 10,000 person-years. SGLT2i were associated with similarly increased risk of genital infection in both age groups (incidence rate ratio in those <70: 2.27 [2.03, 2.53]; ≥70: 2.16 [1.77, 2.63]). There was no evidence of an increased risk of volume depletion, poor micturition control, urinary frequency, falls or amputation with SGLT2i in either age group. In those ≥70, HbA reduction was similar between SGLT2i and DPP4i (-0.3 mmol/mol [-1.6, 1.1], -0.02% [0.1, 0.1]), but in those <70, SGLT2i were more effective (-4 mmol/mol [4.8, -3.1], -0.4% [-0.4, -0.3]).
CONCLUSIONS/INTERPRETATION: Causal analysis suggests SGLT2i are effective in adults aged ≥70 years, but increase risk for genital infections and diabetic ketoacidosis. Our study extends RCT evidence to older adults with type 2 diabetes.
目的/假设：老年人在临床试验中代表性不足，这意味着在该年龄段人群中，降糖药物的获益和风险尚不清楚。本研究旨在使用因果分析评估钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）在 70 岁以上的 2 型糖尿病患者中的安全性和有效性。
使用与医院相关的英国初级保健数据（临床实践研究数据链接，2013-2020 年），比较 SGLT2i 与二肽基肽酶-4 抑制剂（DPP4i）相比，在起始治疗时的不良事件和有效性。分析按年龄分层：<70 岁（SGLT2i 组 n=66810，DPP4i 组 n=76172）；≥70 岁（SGLT2i 组 n=10419，DPP4i 组 n=33434）。使用工具变量因果推理方法和处方偏好作为工具评估结局。
在≥70 岁的患者中，SGLT2i 增加了糖尿病酮症酸中毒的风险（与 DPP4i 相比，发生率比：3.82 [95%CI 1.12, 13.03]），但在<70 岁的患者中没有（1.12 [0.41, 3.04]）。然而，在≥70 岁的患者中，SGLT2i 的发生率较低（每 10000 人年 29.6 [29.5, 29.7]）。SGLT2i 在两个年龄组中均与生殖器感染风险增加相关（<70 岁：发生率比 2.27 [2.03, 2.53]；≥70 岁：2.16 [1.77, 2.63]）。在任何年龄组中，SGLT2i 均未增加容量耗竭、排尿控制不良、尿频、跌倒或截肢的风险。在≥70 岁的患者中，SGLT2i 和 DPP4i 治疗后 HbA1c 降低程度相似（-0.3mmol/mol [-1.6, 1.1]，-0.02% [-0.1, 0.1]），但在<70 岁的患者中，SGLT2i 更为有效（-4mmol/mol [4.8, -3.1]，-0.4% [-0.4, -0.3]）。
结论/解释：因果分析表明，SGLT2i 对≥70 岁的成年人有效，但会增加生殖器感染和糖尿病酮症酸中毒的风险。本研究将 RCT 证据扩展至 2 型糖尿病的老年患者。
