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替尔泊肽用于非肥胖的老年2型糖尿病患者:SURPASS临床试验的事后分析

Tirzepatide for Older Adults with Type 2 Diabetes and Without Obesity: A Post Hoc Analysis of the SURPASS Clinical Trials.

作者信息

Rasouli Neda, Wilding John P H, Kwan Anita Y M, Paik Jim S, Sharma Palash, Peleshok Jennifer

机构信息

Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, School of Medicine, University of Colorado, VA Eastern Colorado Health Care System, Aurora, CO, USA.

Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

出版信息

Diabetes Ther. 2025 Apr;16(4):701-715. doi: 10.1007/s13300-025-01711-0. Epub 2025 Feb 28.

Abstract

INTRODUCTION

Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist approved in the US for treating type 2 diabetes (T2D) and obesity, has demonstrated significant improvements in glycated hemoglobin A1c (HbA1c) and clinically meaningful weight loss in the SURPASS-1 to -5 clinical trials. This post hoc analysis examined the safety and efficacy results for tirzepatide in older participants with T2D who do not have obesity.

METHODS

A post hoc analysis was conducted on a subgroup of participants aged ≥ 65 years with a body mass index (BMI) < 30 kg/m amongst the pooled SURPASS-1 through -5 clinical trial populations. Primary efficacy endpoints and safety were assessed for both this subgroup and overall pooled populations.

RESULTS

Participants aged ≥ 65 years with BMI < 30 kg/m treated with tirzepatide experienced clinically meaningful HbA1c reduction (- 1.97 to - 2.10%) regardless of the assigned randomized maintenance dose. In contrast, a dose-proportional HbA1c decrease was observed in the overall population. Weight reduction in this subgroup was dose-proportional but numerically lower than in the overall population. Older participants without obesity were more likely to discontinue treatment due to adverse events (AEs), although the overall incidence of AEs was low in this subgroup. The incidence of hypoglycemia in this group was consistent with that of the overall cohort, regardless of concurrent insulin or sulfonylurea use.

CONCLUSIONS

Tirzepatide may be an effective treatment for older adults without obesity, and in this post hoc analysis, it was associated with clinically relevant HbA1c reduction and dose-proportional weight loss without increasing hypoglycemic risk.

摘要

引言

替尔泊肽是一种每周注射一次的葡萄糖依赖性促胰岛素多肽/胰高血糖素样肽-1受体激动剂,在美国被批准用于治疗2型糖尿病(T2D)和肥胖症,在SURPASS-1至-5临床试验中已证明糖化血红蛋白A1c(HbA1c)有显著改善,且体重减轻具有临床意义。这项事后分析研究了替尔泊肽在无肥胖症的老年T2D患者中的安全性和疗效结果。

方法

对SURPASS-1至-5临床试验合并人群中年龄≥65岁、体重指数(BMI)<30kg/m²的参与者亚组进行事后分析。对该亚组和总体合并人群评估主要疗效终点和安全性。

结果

无论分配的随机维持剂量如何,接受替尔泊肽治疗的年龄≥65岁、BMI<30kg/m²的参与者HbA1c均有具有临床意义的降低(-1.97%至-2.10%)。相比之下,总体人群中观察到HbA1c呈剂量依赖性降低。该亚组的体重减轻与剂量成比例,但数值低于总体人群。无肥胖症的老年参与者因不良事件(AE)停药的可能性更大,尽管该亚组AE的总体发生率较低。无论是否同时使用胰岛素或磺脲类药物,该组低血糖的发生率与总体队列一致。

结论

替尔泊肽可能是无肥胖症老年人的有效治疗方法,在这项事后分析中,它与具有临床相关性的HbA1c降低和剂量依赖性体重减轻相关,且未增加低血糖风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ed0/11925828/5d557bdc4378/13300_2025_1711_Fig1_HTML.jpg

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