Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida (H.T., Y.L.).
Division of Endocrinology, Diabetes and Metabolism, College of Medicine, University of Florida, Gainesville, Florida (W.T.D.).
Ann Intern Med. 2024 Aug;177(8):1004-1015. doi: 10.7326/M24-0329. Epub 2024 Jul 16.
A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes.
To investigate the association between GLP-1 RAs, compared with sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is), and risk for suicidal ideation and behaviors in older adults with type 2 diabetes (T2D).
Two target trial emulation studies comparing propensity score (PS)-matched cohorts for GLP-1 RAs versus SGLT2is and GLP-1 RAs versus DPP4is.
U.S. national Medicare administrative data from January 2017 to December 2020.
Older adults (≥66 years) with T2D; no record of suicidal ideation or behaviors; and a first prescription for a GLP-1 RA, SGLT2i, or DPP4i.
The primary end point was a composite of suicidal ideation and behaviors. New GLP-1 RA users were matched 1:1 on PS to new users of an SGLT2i or DPP4i in each pairwise comparison. A Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% CIs within matched groups.
This study included 21 807 pairs of patients treated with a GLP-1 RA versus an SGLT2i and 21 402 pairs of patients treated with a GLP-1 RA versus a DPP4i. The HR of suicidal ideation and behaviors associated with GLP-1 RAs relative to SGLT2is was 1.07 (95% CI, 0.80 to 1.45; rate difference, 0.16 [CI, -0.53 to 0.86] per 1000 person-years); the HR relative to DPP4is was 0.94 (CI, 0.71 to 1.24; rate difference, -0.18 [CI, -0.92 to 0.57] per 1000 person-years).
Low event rate; imprecise estimates; unmeasured confounders, such as body mass index; and potential misclassification of outcomes.
Among Medicare beneficiaries with T2D, this study found no clear increased risk for suicidal ideation and behaviors with GLP-1 RAs, although estimates were imprecise and a modest adverse risk could not be ruled out.
American Foundation for Pharmaceutical Education, Pharmaceutical Research and Manufacturers of America Foundation, National Institute on Aging, and National Institute of Diabetes and Digestive and Kidney Diseases.
最近出现了一个主要关注点，即基于国际疾病分类代码，胰高血糖素样肽-1 受体激动剂 (GLP-1 RA) 与自杀意念和行为的风险增加之间可能存在关联。
研究 GLP-1 RA 与钠-葡萄糖共转运蛋白 2 抑制剂 (SGLT2i) 或二肽基肽酶-4 抑制剂 (DPP4i) 相比，在患有 2 型糖尿病 (T2D) 的老年患者中与自杀意念和行为风险之间的关联。
两项以目标试验模拟研究，比较了 GLP-1 RA 与 SGLT2i 以及 GLP-1 RA 与 DPP4i 的倾向评分 (PS) 匹配队列。
美国 2017 年 1 月至 2020 年 12 月国家医疗保险管理数据。
≥66 岁的 T2D 患者；无自杀意念或行为记录；并首次开处 GLP-1 RA、SGLT2i 或 DPP4i。
主要终点是自杀意念和行为的综合指标。在每一对比较中，新 GLP-1 RA 使用者与新 SGLT2i 或 DPP4i 使用者按 PS 进行 1:1 匹配。使用 Cox 比例风险回归估计匹配组内的风险比 (HR) 和 95%CI。
这项研究纳入了 21807 对接受 GLP-1 RA 治疗与 SGLT2i 治疗的患者和 21402 对接受 GLP-1 RA 治疗与 DPP4i 治疗的患者。与 SGLT2i 相比，GLP-1 RA 与自杀意念和行为相关的 HR 为 1.07（95%CI，0.80 至 1.45；率差，每 1000 人年 0.16 [CI，-0.53 至 0.86]）；与 DPP4i 相比，HR 为 0.94（CI，0.71 至 1.24；率差，每 1000 人年-0.18 [CI，-0.92 至 0.57]）。
事件发生率低；估计不精确；未测量的混杂因素，如体重指数；以及结局可能存在错误分类。
在接受 T2D 治疗的医疗保险受益人群中，这项研究未发现 GLP-1 RA 明显增加自杀意念和行为的风险，尽管估计不精确，但不能排除存在适度的不利风险。
美国制药教育基金会、美国制药研究和制造商协会基金会、美国国家老龄化研究所和美国国家糖尿病、消化和肾脏疾病研究所。
