{"title":"减肥是胰高血糖素样肽1 （GLP-1）受体激动剂改善A1C的主要驱动因素吗？2.5年临床实践分析","authors":"Marwa Al-Badri, Shilton Dhaver, Osama Hamdy","doi":"10.1111/1753-0407.70054","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, GLP-1 RAs also induce weight loss by suppressing appetite via hypothalamic pathways. However, it remains unclear whether weight reduction is the primary driver of glycemic improvement.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We retrospectively evaluated 256 patients with T2D who were treated with exenatide (<i>n</i> = 84), dulaglutide (<i>n</i> = 99), or semaglutide (<i>n</i> = 73) for 2.5 years without interruption in real-world clinical practice. Body weight and A1C were measured every 6 months. Baseline characteristics included an average age of 61.8 ± 11.9 years, 51.5% female, diabetes duration of 12.9 ± 8.3 years, weight of 103.1 ± 20.7 kg, BMI of 35.7 ± 7.5 kg/m<sup>2</sup>, and A1C of 8.2% ± 1.5%. Patients were stratified into tertiles based on percentage weight change at 2.5 years within the overall cohort and for each GLP-1 RA group.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The first tertile experienced an average weight loss of −12.2% ± 5.7% (<i>p</i> < 0.0001), the second tertile lost −3.5% ± 1.4% (<i>p</i> < 0.0001), and the third tertile gained +2.8% ± 3.4% (<i>p</i> < 0.0001). The average changes in A1C were − 0.98 ± 1.8% (<i>p</i> < 0.0001), −0.56% ± 1.4% (<i>p</i> < 0.001), and −0.19% ± 1.9% (<i>p</i> = 0.4), respectively. A1C strongly correlated with weight change (<i>p</i> < 0.001). The same observations were reproducible in each medication group.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>These findings suggest that the long-term improvement in glycemic control associated with GLP-1 RA therapy is primarily driven by weight loss rather than any other intrinsic effect of GLP-1 RA. This highlights the importance of weight reduction as a key therapeutic target for optimizing glycemic outcomes in patients with T2D receiving GLP-1 RAs.</p>\n \n <div>\n \n <figure>\n <div><picture>\n <source></source></picture><p></p>\n </div>\n </figure>\n </div>\n </section>\n </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 1","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757277/pdf/","citationCount":"0","resultStr":"{\"title\":\"Is Weight Loss the Main Driver for A1C Improvement by Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists? A 2.5-Year Analysis in Real-World Clinical Practice\",\"authors\":\"Marwa Al-Badri, Shilton Dhaver, Osama Hamdy\",\"doi\":\"10.1111/1753-0407.70054\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, GLP-1 RAs also induce weight loss by suppressing appetite via hypothalamic pathways. However, it remains unclear whether weight reduction is the primary driver of glycemic improvement.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We retrospectively evaluated 256 patients with T2D who were treated with exenatide (<i>n</i> = 84), dulaglutide (<i>n</i> = 99), or semaglutide (<i>n</i> = 73) for 2.5 years without interruption in real-world clinical practice. Body weight and A1C were measured every 6 months. Baseline characteristics included an average age of 61.8 ± 11.9 years, 51.5% female, diabetes duration of 12.9 ± 8.3 years, weight of 103.1 ± 20.7 kg, BMI of 35.7 ± 7.5 kg/m<sup>2</sup>, and A1C of 8.2% ± 1.5%. Patients were stratified into tertiles based on percentage weight change at 2.5 years within the overall cohort and for each GLP-1 RA group.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The first tertile experienced an average weight loss of −12.2% ± 5.7% (<i>p</i> < 0.0001), the second tertile lost −3.5% ± 1.4% (<i>p</i> < 0.0001), and the third tertile gained +2.8% ± 3.4% (<i>p</i> < 0.0001). The average changes in A1C were − 0.98 ± 1.8% (<i>p</i> < 0.0001), −0.56% ± 1.4% (<i>p</i> < 0.001), and −0.19% ± 1.9% (<i>p</i> = 0.4), respectively. A1C strongly correlated with weight change (<i>p</i> < 0.001). The same observations were reproducible in each medication group.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>These findings suggest that the long-term improvement in glycemic control associated with GLP-1 RA therapy is primarily driven by weight loss rather than any other intrinsic effect of GLP-1 RA. This highlights the importance of weight reduction as a key therapeutic target for optimizing glycemic outcomes in patients with T2D receiving GLP-1 RAs.</p>\\n \\n <div>\\n \\n <figure>\\n <div><picture>\\n <source></source></picture><p></p>\\n </div>\\n </figure>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":189,\"journal\":{\"name\":\"Journal of Diabetes\",\"volume\":\"17 1\",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-01-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757277/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Diabetes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/1753-0407.70054\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Diabetes","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/1753-0407.70054","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Is Weight Loss the Main Driver for A1C Improvement by Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists? A 2.5-Year Analysis in Real-World Clinical Practice
Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, GLP-1 RAs also induce weight loss by suppressing appetite via hypothalamic pathways. However, it remains unclear whether weight reduction is the primary driver of glycemic improvement.
Methods
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice. Body weight and A1C were measured every 6 months. Baseline characteristics included an average age of 61.8 ± 11.9 years, 51.5% female, diabetes duration of 12.9 ± 8.3 years, weight of 103.1 ± 20.7 kg, BMI of 35.7 ± 7.5 kg/m2, and A1C of 8.2% ± 1.5%. Patients were stratified into tertiles based on percentage weight change at 2.5 years within the overall cohort and for each GLP-1 RA group.
Results
The first tertile experienced an average weight loss of −12.2% ± 5.7% (p < 0.0001), the second tertile lost −3.5% ± 1.4% (p < 0.0001), and the third tertile gained +2.8% ± 3.4% (p < 0.0001). The average changes in A1C were − 0.98 ± 1.8% (p < 0.0001), −0.56% ± 1.4% (p < 0.001), and −0.19% ± 1.9% (p = 0.4), respectively. A1C strongly correlated with weight change (p < 0.001). The same observations were reproducible in each medication group.
Conclusions
These findings suggest that the long-term improvement in glycemic control associated with GLP-1 RA therapy is primarily driven by weight loss rather than any other intrinsic effect of GLP-1 RA. This highlights the importance of weight reduction as a key therapeutic target for optimizing glycemic outcomes in patients with T2D receiving GLP-1 RAs.
期刊介绍：
Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation.
The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.
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