Association of Glucagon-Like Peptide-1 Receptor Agonists With Cancer Risk in Older Adults With Type 2 Diabetes.

Obesity (Silver Spring, Md.) Pub Date : 2025-08-21 DOI:10.1002/oby.24366

Ying Lu, Hao Dai, Huilin Tang, William T Donahoo, Thomas J George, Ramon C Sun, Sizun Jiang, Aik Choon Tan, Yi Guo, Jonathan D Licht, John M Allen, Kelvin P Lee, Jingchuan Guo, Jiang Bian

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Abstract

Objective: The real-world evidence on the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and cancer risk remains limited and mixed.

Methods: In 2013-2020 national Medicare claims data, we included cancer-naïve patients with type 2 diabetes (T2D). We identified those who initiated GLP-1 RA, sodium-glucose cotransporter 2 inhibitor (SGLT2i), or dipeptidyl peptidase 4 inhibitor (DPP4i) and conducted 1:1 propensity score matching for confounding adjustment. Cox proportional hazards models were used to estimate hazard ratios (HR) of nine obesity-associated cancers (thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate cancer).

Results: In the matched GLP-1RA versus SGLT2i cohort (n = 21,362 pairs), GLP-1RA users had similar overall cancer risk with SGLT2i users (HR, 1.03 [95% CI, 0.95-1.12]), but GLP-1RAs were associated with an increased kidney cancer risk (HR, 1.43 [1.06-1.92]). In the matched GLP-1RA versus DPP4i cohort (n = 20,962 pairs), the GLP-1RA versus DPP4i comparison showed no significant difference in overall cancer risk (HR, 0.96 [0.89-1.04]) but revealed a significantly elevated endometrial cancer risk (HR, 1.55 [1.01-2.37]).

Conclusion: GLP-1RAs might be associated with an increased risk of certain cancer types. Future studies are needed to validate the potential tumorigenic risk associated with GLP1-RAs.

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胰高血糖素样肽-1受体激动剂与老年2型糖尿病患者癌症风险的关系

目的：关于胰高血糖素样肽-1受体激动剂（GLP-1RAs）与癌症风险之间关系的真实证据仍然有限且混杂。方法：在2013-2020年国家医疗保险索赔数据中，我们纳入cancer-naïve 2型糖尿病（T2D）患者。我们确定了那些启动GLP-1 RA，钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）或二肽基肽酶4抑制剂（DPP4i）的患者，并进行1:1倾向评分匹配以进行混杂校正。Cox比例风险模型用于估计9种肥胖相关癌症（甲状腺癌、胰腺癌、膀胱癌、结肠直肠癌、肺癌、肾癌、乳腺癌、子宫内膜癌和前列腺癌）的风险比（HR）。结果：在匹配的GLP-1RA与SGLT2i队列中（n = 21,362对），GLP-1RA使用者与SGLT2i使用者具有相似的总体癌症风险（HR, 1.03 [95% CI, 0.95-1.12]），但GLP-1RAs与肾癌风险增加相关（HR, 1.43[1.06-1.92]）。在匹配的GLP-1RA与DPP4i队列（n = 20,962对）中，GLP-1RA与DPP4i的比较显示总体癌症风险无显著差异（HR, 0.96[0.89-1.04]），但显示子宫内膜癌风险显著升高（HR, 1.55[1.01-2.37]）。结论：GLP-1RAs可能与某些癌症类型的风险增加有关。未来的研究需要验证GLP1-RAs相关的潜在致瘤风险。

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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Obesity (Silver Spring, Md.)

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