Safety considerations of semaglutide in the potential treatment of Alzheimer's disease: A pooled analysis of semaglutide in adults aged ≥ 65 years

IF 4.9 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-05-06 DOI:10.1002/trc2.70076

Marwan Sabbagh, Cristina Boschini, Sharon Cohen, Magnus Fugger, Frank Jessen, Sune Dandanell, Sue D. Pedersen, Luis Rafael Solís Tarazona, Vanita R. Aroda

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Abstract

INTRODUCTION

The evoke/evoke+ trials are investigating semaglutide in a population with early Alzheimer's disease (AD). Specific analyses of semaglutide safety data in older adults are limited; therefore, in the current analysis, we aimed to evaluate safety considerations with semaglutide in adults ≥ 65 years.

METHODS

Adverse event (AE) data from three semaglutide phase 3a programs in participants ≥ 65 years with type 2 diabetes and/or overweight/obesity were pooled. Change in body weight was also assessed in a smaller subset of participants ≥ 65 years.

RESULTS

The analysis included 3529 participants ≥ 65 years. Baseline mean age and body mass index in participants ≥ 65 years were 69.3 to 70.2 years and 29.7 to 35.4 kg/m², respectively, compared to 47.8 to 58.5 years and 31.3 to 36.7 kg/m² in the overall population. AEs with semaglutide occurred in 73.6% to 92.4% of participants ≥ 65 years versus 73.2% to 90.8% of the overall population. AEs with semaglutide leading to permanent discontinuation appeared to be more frequent in participants ≥ 65 years (9.3%–12.4%) versus the overall population (5.7%–8.7%). Gastrointestinal disorders were the most frequently reported AEs with semaglutide in participants ≥ 65 years (44.6%–73.8%) and in the overall population (39.1%–73.4%). Participants aged ≥ 65 years receiving semaglutide had an estimated weight loss of 3.8% at week 52 compared to 0.1% with placebo.

DISCUSSION

Age ≥ 65 years did not appear to affect the safety considerations of semaglutide. The ongoing evoke/evoke+ trials will elucidate the balance of efficacy and safety in the treatment of early AD with semaglutide.

Highlights

This was a post hoc analysis evaluating adverse event (AE) data of semaglutide in people ≥ 65 years.
The most common AE with semaglutide was gastrointestinal (GI).
GI event rates were similar in people ≥ 65 years and the overall study populations.

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西马鲁肽在阿尔茨海默病潜在治疗中的安全性考虑：一项对≥65岁成人西马鲁肽的汇总分析

evoke/evoke+试验正在研究semaglutide在早期阿尔茨海默病（AD）人群中的作用。对西马鲁肽在老年人中的安全性数据的具体分析是有限的；因此，在当前的分析中，我们的目的是评估semaglutide在≥65岁成人中的安全性考虑。方法汇总来自3个semaglutide 3a期项目的不良事件（AE）数据，这些受试者年龄≥65岁，患有2型糖尿病和/或超重/肥胖。在年龄≥65岁的一小部分参与者中，体重变化也被评估。结果分析纳入3529名≥65岁的参与者。≥65岁参与者的基线平均年龄和体重指数分别为69.3 ~ 70.2岁和29.7 ~ 35.4 kg/m2，而总体人群的基线平均年龄和体重指数分别为47.8 ~ 58.5岁和31.3 ~ 36.7 kg/m2。在≥65岁的受试者中，73.6% ~ 92.4%的患者发生了西马鲁肽不良事件，而在总体人群中，这一比例为73.2% ~ 90.8%。与总体人群（5.7%-8.7%）相比，semaglutide导致永久停药的ae在≥65岁的参与者中更为常见（9.3%-12.4%）。在≥65岁的受试者（44.6%-73.8%）和总体人群（39.1%-73.4%）中，胃肠道疾病是西马鲁肽最常报告的ae。≥65岁的受试者接受西马鲁肽治疗后，在第52周体重减轻3.8%，而安慰剂组为0.1%。年龄≥65岁似乎不影响西马鲁肽的安全性考虑。正在进行的evoke/evoke+试验将阐明西马鲁肽治疗早期AD的有效性和安全性的平衡。这是一项评价西马鲁肽在≥65岁人群中不良事件（AE）数据的事后分析。西马鲁肽最常见的AE是胃肠道（GI）。在≥65岁的人群和总体研究人群中，GI事件发生率相似。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.