The potential adverse effects of hypodermic glucagon‐like peptide ‐1 receptor agonist on patients with type 2 diabetes: A population‐based study

Abstract Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long‐term safety of GLP‐1 RAs remains insufficiently st...

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Main Authors: Zhiyuan Cheng, Shuang Wang, Fu‐rong Li, Cheng Jin, Chunbao Mo, Jing Zheng, Xia Li, Fengchao Liang, Jinkui Yang, Dongfeng Gu
Format: Article
Language:English
Published: Wiley 2024-10-01
Series:Journal of Diabetes
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Online Access:https://doi.org/10.1111/1753-0407.70013
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author Zhiyuan Cheng
Shuang Wang
Fu‐rong Li
Cheng Jin
Chunbao Mo
Jing Zheng
Xia Li
Fengchao Liang
Jinkui Yang
Dongfeng Gu
author_facet Zhiyuan Cheng
Shuang Wang
Fu‐rong Li
Cheng Jin
Chunbao Mo
Jing Zheng
Xia Li
Fengchao Liang
Jinkui Yang
Dongfeng Gu
author_sort Zhiyuan Cheng
collection DOAJ
description Abstract Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long‐term safety of GLP‐1 RAs remains insufficiently studied. This study aimed to provide real‐world evidence on potential adverse outcomes associated with GLP‐1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function. Methods We conducted a retrospective cohort study involving 7746 T2D patients on GLP‐1 RAs in Shenzhen, China. They were compared with 124 371 metformin‐only users and 36 146 insulin‐only users, forming two therapy control groups. GLP‐1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP‐1 RAs use. Results Compared with metformin‐only users, GLP‐1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24–3.24), acute nephritis (3.20, 2.17–4.70), kidney failure (3.73, 2.74–5.08), thyroid cancer (2.25, 1.23–4.10), and thyroid dysfunction (1.27, 1.00–1.63), respectively; Similar results were also found when compared with insulin‐only users. Importantly, long‐term (≥12 months) GLP‐1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction. Conclusion Compared with traditional T2D treatments, GLP‐1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP‐1 RAs. Further validation is crucial across diverse populations.
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spelling doaj-art-bb757573ac26405dbf27de4cef7c0d182025-08-20T02:50:48ZengWileyJournal of Diabetes1753-03931753-04072024-10-011610n/an/a10.1111/1753-0407.70013The potential adverse effects of hypodermic glucagon‐like peptide ‐1 receptor agonist on patients with type 2 diabetes: A population‐based studyZhiyuan Cheng0Shuang Wang1Fu‐rong Li2Cheng Jin3Chunbao Mo4Jing Zheng5Xia Li6Fengchao Liang7Jinkui Yang8Dongfeng Gu9School of Public Health and Emergency Management Southern University of Science and Technology Shenzhen ChinaShenzhen Health Development Research and Data Management Center Shenzhen ChinaSchool of Public Health and Emergency Management Southern University of Science and Technology Shenzhen ChinaSchool of Public Health and Emergency Management Southern University of Science and Technology Shenzhen ChinaSchool of Public Health and Emergency Management Southern University of Science and Technology Shenzhen ChinaShenzhen Health Development Research and Data Management Center Shenzhen ChinaSchool of Public Health and Emergency Management Southern University of Science and Technology Shenzhen ChinaSchool of Public Health and Emergency Management Southern University of Science and Technology Shenzhen ChinaDepartment of Endocrinology, Beijing Tongren Hospital Capital Medical University Beijing ChinaSchool of Public Health and Emergency Management Southern University of Science and Technology Shenzhen ChinaAbstract Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long‐term safety of GLP‐1 RAs remains insufficiently studied. This study aimed to provide real‐world evidence on potential adverse outcomes associated with GLP‐1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function. Methods We conducted a retrospective cohort study involving 7746 T2D patients on GLP‐1 RAs in Shenzhen, China. They were compared with 124 371 metformin‐only users and 36 146 insulin‐only users, forming two therapy control groups. GLP‐1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP‐1 RAs use. Results Compared with metformin‐only users, GLP‐1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24–3.24), acute nephritis (3.20, 2.17–4.70), kidney failure (3.73, 2.74–5.08), thyroid cancer (2.25, 1.23–4.10), and thyroid dysfunction (1.27, 1.00–1.63), respectively; Similar results were also found when compared with insulin‐only users. Importantly, long‐term (≥12 months) GLP‐1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction. Conclusion Compared with traditional T2D treatments, GLP‐1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP‐1 RAs. Further validation is crucial across diverse populations.https://doi.org/10.1111/1753-0407.70013clinical adverse outcomesGLP‐1 receptor agoniststype 2 diabetes
spellingShingle Zhiyuan Cheng
Shuang Wang
Fu‐rong Li
Cheng Jin
Chunbao Mo
Jing Zheng
Xia Li
Fengchao Liang
Jinkui Yang
Dongfeng Gu
The potential adverse effects of hypodermic glucagon‐like peptide ‐1 receptor agonist on patients with type 2 diabetes: A population‐based study
Journal of Diabetes
clinical adverse outcomes
GLP‐1 receptor agonists
type 2 diabetes
title The potential adverse effects of hypodermic glucagon‐like peptide ‐1 receptor agonist on patients with type 2 diabetes: A population‐based study
title_full The potential adverse effects of hypodermic glucagon‐like peptide ‐1 receptor agonist on patients with type 2 diabetes: A population‐based study
title_fullStr The potential adverse effects of hypodermic glucagon‐like peptide ‐1 receptor agonist on patients with type 2 diabetes: A population‐based study
title_full_unstemmed The potential adverse effects of hypodermic glucagon‐like peptide ‐1 receptor agonist on patients with type 2 diabetes: A population‐based study
title_short The potential adverse effects of hypodermic glucagon‐like peptide ‐1 receptor agonist on patients with type 2 diabetes: A population‐based study
title_sort potential adverse effects of hypodermic glucagon like peptide 1 receptor agonist on patients with type 2 diabetes a population based study
topic clinical adverse outcomes
GLP‐1 receptor agonists
type 2 diabetes
url https://doi.org/10.1111/1753-0407.70013
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