替尔泊肽治疗的谷氨酸脱羧酶抗体阳性个体的糖化血红蛋白和体重改善：SURPASS事后分析

Improved HbA1c and Body Weight in GADA-Positive Individuals Treated With Tirzepatide: A Post Hoc Analysis of SURPASS.

作者信息

Peters Anne L, Buzzetti Raffaella, Lee Clare J, Pavo Imre, Liu Minzhi, Karanikas Chrisanthi A, Paik Jim S

机构信息

University of Southern California Clinical Diabetes Program, Keck School of Medicine of the University of Southern California, Los Angeles, Los Angeles, CA 90033, USA.

Department of Experimental Medicine, Sapienza University of Rome, Rome 00160, Italy.

出版信息

J Clin Endocrinol Metab. 2025 Mar 17;110(4):e962-e969. doi: 10.1210/clinem/dgae372.

DOI:10.1210/clinem/dgae372

PMID:38824910

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11913103/

Abstract

CONTEXT

People with clinically diagnosed type 2 diabetes (T2D) but positive antiglutamic acid decarboxylase autoantibodies (GADA), referred to here as latent autoimmune diabetes in adults (LADA), may experience more rapid glycemic deterioration than those with T2D and may benefit from effective diabetes treatment with additional metabolic benefits.

OBJECTIVE

This work aimed to assess glycated hemoglobin A1c (HbA1c) and body weight (BW) changes associated with tirzepatide in GADA-positive vs GADA-negative participants with a clinical T2D diagnosis.

METHODS

Post hoc analyses based on pooled data from SURPASS 2-5, using mixed-model repeated measures from the efficacy analysis set, adjusting for study and baseline covariates including age, sex, baseline values, body mass index (BMI), and GADA status, were conducted on 3791 individuals. Intervention included tirzepatide (5, 10, 15 mg). Main outcome measure included change from baseline in HbA1c at weeks 40 (SURPASS-2, -3, -5) and 42 (SURPASS-4) by GADA status.

RESULTS

In participants with confirmed GADA status, 3671 (96.8%) were GADA negative and 120 (3.2%) were GADA positive (76 [63.3%] with low and 44 [36.7%] with high GADA levels). Baseline characteristics were similar between groups, except for slightly lower BMI in GADA-positive vs GADA-negative participants (mean [SD] BMI 32.2 [6.1] vs 33.6 [6.3]). At week 40/42, both groups achieved robust reductions in HbA1c (-2.11% vs -2.32%) and BW (-9.2 kg vs -9.6 kg) (P < .001, both groups). HbA1c reductions were greater in GADA-negative participants (estimated difference [95% CI]: 0.21% [0.03, 0.39]; P = .024) and BW reductions did not differ between groups (0.38 kg [-0.99, 1.75]; P = .588).

CONCLUSION

In this post hoc analysis, tirzepatide was associated with substantial reductions in HbA1c and BW irrespective of GADA status in adults diagnosed with T2D, suggesting that tirzepatide may improve glycemic control in individuals with LADA.

摘要

背景

临床诊断为2型糖尿病（T2D）但谷氨酸脱羧酶自身抗体（GADA）呈阳性的患者，在此称为成人隐匿性自身免疫性糖尿病（LADA），其血糖恶化速度可能比T2D患者更快，可能从有效的糖尿病治疗中获益并获得额外的代谢益处。

目的

本研究旨在评估替尔泊肽对临床诊断为T2D的GADA阳性与GADA阴性参与者糖化血红蛋白A1c（HbA1c）和体重（BW）的影响。

方法

基于SURPASS 2 - 5的汇总数据进行事后分析，使用疗效分析集中的混合模型重复测量方法，对年龄、性别、基线值、体重指数（BMI）和GADA状态等研究和基线协变量进行调整，共纳入3791名个体。干预措施包括替尔泊肽（5、10、15mg）。主要结局指标包括在第40周（SURPASS - 2、- 3、- 5）和第42周（SURPASS - 4）时，根据GADA状态，HbA1c相对于基线的变化。

结果

在GADA状态确诊的参与者中，3671名（96.8%）为GADA阴性，120名（3.2%）为GADA阳性（76名[63.3%]GADA水平低，44名[36.7%]GADA水平高）。两组的基线特征相似，但GADA阳性参与者的BMI略低于GADA阴性参与者（平均[标准差]BMI：32.2[6.1] vs 33.6[6.3]）。在第40/42周时，两组的HbA1c（-2.11% vs -2.32%）和BW（-9.2kg vs -9.6kg）均显著降低（两组P均<0.001）。GADA阴性参与者的HbA1c降低幅度更大（估计差异[95%CI]：0.21%[0.03，0.39]；P = 0.024），而两组的BW降低幅度无差异（0.38kg[-0.99，1.75]；P = 0.588）。