真实世界临床实践中2型糖尿病患者对胰高血糖素样肽-1受体激动剂反应的异质性：来自糖尿病患者虚拟队列研究（DPV注册研究）——一项IMI-SOPHIA研究的见解
Heterogeneity in response to GLP-1 receptor agonists in type 2 diabetes in real-world clinical practice: insights from the DPV register - an IMI-SOPHIA study.
作者信息
Heni Martin, Frühwald Lisa, Karges Wolfram, Naudorf Michael, Niemöller Kathrin, Pagnia Frank, Reindel Jörg, Seufert Jochen, Ufer Gisa, Wagner Christian, Holl Reinhard W, Prinz Nicole
机构信息
Division of Endocrinology and Diabetology, Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany.
Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, Tübingen, Germany.
出版信息
Diabetologia. 2025 May 22. doi: 10.1007/s00125-025-06448-w.
AIMS/HYPOTHESIS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a cornerstone in type 2 diabetes management. In this study we evaluated heterogeneity in body weight and glycaemic responses to the initiation of liraglutide, semaglutide or dulaglutide in real-world clinical practice.
METHODS
Data from 4467 adults with type 2 diabetes in the Diabetes Patient Follow-up (DPV) registry were analysed, focusing on changes in HbA and body weight over 6 months following initiation of a GLP-1 RA. We categorised participants based on their response: HbA reduction only, weight loss only, both or neither. This analysis was part of the IMI-Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (IMI-SOPHIA) project.
RESULTS
At 6 months' follow-up the median absolute HbA reduction was 5.3 mmol/mol (IQR 13.9, -1.0) (0.49% [1.27, -0.09]) and relative body weight reduction was 1.43% (4.26, 0). Only 14% of participants achieved meaningful reductions in both HbA (absolute reduction ≥5.5 mmol/mol [0.5%]) and body weight (relative reduction ≥5%). Men and those with a higher baseline HbA were more likely to show an HbA only response (36% of participants; both p<0.001), while older individuals and those with a longer diabetes duration were more likely to experience a weight-only response (7% of participants; both p<0.001). Higher baseline body weight and lower eGFR (both p<0.05) correlated with greater weight reduction, whereas lower baseline HbA and longer diabetes duration were linked to smaller HbA reductions (both p<0.001).
CONCLUSIONS/INTERPRETATION: There is significant heterogeneity in responses to GLP-1 RA therapy among individuals with type 2 diabetes in routine clinical practice. However, in our study a substantial proportion achieved a reduction in either body weight or HbA. Future studies should explore why some individuals achieve either weight loss or HbA reduction but not both.
目的/假设：胰高血糖素样肽-1受体激动剂（GLP-1 RAs）是2型糖尿病管理的基石。在本研究中，我们评估了在现实临床实践中，起始使用利拉鲁肽、司美格鲁肽或度拉糖肽后体重和血糖反应的异质性。
方法
分析了糖尿病患者随访（DPV）登记处4467例2型糖尿病成人患者的数据，重点关注起始使用GLP-1 RA后6个月内糖化血红蛋白（HbA）和体重的变化。我们根据参与者的反应进行分类：仅HbA降低、仅体重减轻、两者均有或两者均无。该分析是IMI-肥胖表型分层以优化未来肥胖治疗（IMI-SOPHIA）项目的一部分。
结果
在6个月的随访中，HbA的中位绝对降低值为5.3 mmol/mol（四分位间距13.9，-1.0）（0.49% [1.27，-0.09]），相对体重降低值为1.43%（4.26，0）。只有14%的参与者在HbA（绝对降低≥5.5 mmol/mol [0.5%]）和体重（相对降低≥5%）方面均实现了有意义的降低。男性和基线HbA较高的参与者更有可能仅出现HbA反应（占参与者的36%；两者p<0.001），而年龄较大和糖尿病病程较长的参与者更有可能仅出现体重反应（占参与者的7%；两者p<0.001）。较高的基线体重和较低的估算肾小球滤过率（eGFR）（两者p<0.05）与更大的体重减轻相关，而较低的基线HbA和较长的糖尿病病程与较小的HbA降低相关（两者p<0.001）。
结论/解读：在常规临床实践中，2型糖尿病患者对GLP-1 RA治疗的反应存在显著异质性。然而，在我们的研究中，相当一部分患者实现了体重或HbA的降低。未来的研究应探讨为什么一些患者仅实现了体重减轻或HbA降低，而不是两者都实现。
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