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Use of Glucagon-Like Peptide-1 Receptor Agonists Does Not Increase the Risk of Cancer in Patients with Type 2 Diabetes Mellitus
Mijin Kim, Seung Chan Kim, Jinmi Kim, Bo Hyun Kim
Received March 4, 2024  Accepted May 13, 2024  Published online October 24, 2024  
DOI: https://doi.org/10.4093/dmj.2024.0105    [Epub ahead of print]
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Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes mellitus (T2DM) given their extra-pancreatic effects. However, there are concerns about carcinogenesis in the pancreas and thyroid gland. We aimed to evaluate the site-specific incidence of cancer in patients with T2DM-treated GLP-1 RAs using a nationwide cohort.
Methods
This study included data obtained from the Korean National Health Insurance Service (between 2004 and 2021). The primary outcome was newly diagnosed cancer, and the median follow-up duration for all participants was 8 years.
Results
After propensity score matching, 7,827 participants were analyzed; 2,609 individuals each were included in the GLP-1 RA, diabetes mellitus (DM) control, and non-DM control groups. The incidence rate ratio (IRR) of subsequent cancer in patients with T2DM was 1.73, which was higher than that of individuals without DM, and it increased in both men and women. Analysis of patients with T2DM showed no increased cancer risk associated with the use of GLP-1 RA, and similar results were observed in both men and women. The IRRs of pancreatic cancer (0.74), thyroid cancer (1.32), and medullary thyroid cancer (0.34) did not significantly increase in the GLP-1 RA group compared with those in the DM control group.
Conclusion
There was a 73% higher risk of cancer in patients with T2DM compared with the general population. However, among patients with T2DM, there was no association between the use of GLP-1 RAs and new-onset cancers, including pancreatic and medullary thyroid cancers.
Reviews
Clinical Diabetes & Therapeutics
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Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association
Hyun Jin Kim, Seok O Park, Seung-Hyun Ko, Sang Youl Rhee, Kyu-Yeon Hur, Nan-Hee Kim, Min Kyong Moon, Byung-Wan Lee, Jin Hwa Kim, Kyung Mook Choi
Diabetes Metab J. 2017;41(6):423-429.   Published online December 19, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.6.423
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AbstractAbstract PDFPubReader   

The glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The cardiovascular safety of GLP-1RAs has been assessed in several randomized clinical trials and systematic reviews. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RA may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA.

Citations

Citations to this article as recorded by  
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    Hyun Jin Kim
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Islet Studies and Transplantation
An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass
Suk Chon, Jean-François Gautier
Diabetes Metab J. 2016;40(2):99-114.   Published online April 25, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.2.99
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  • 45 Web of Science
  • 43 Crossref
AbstractAbstract PDFPubReader   

Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a complex and progressive pathogenesis. The two primary mechanisms of T2DM pathogenesis are pancreatic β-cell dysfunction and insulin resistance. Pancreatic β-cell dysfunction is recognized to be a prerequisite for the development of T2DM. Therapeutic modalities that improve β-cell function are considered critical to T2DM management; however, blood glucose control remains a challenge for many patients due to suboptimal treatment efficacy and the progressive nature of T2DM. Incretin-based therapies are now the most frequently prescribed antidiabetic drugs in Korea. Incretin-based therapies are a favorable class of drugs due to their ability to reduce blood glucose by targeting the incretin hormone system and, most notably, their potential to improve pancreatic β-cell function. This review outlines the current understanding of the incretin hormone system in T2DM and summarizes recent updates on the effect of incretin-based therapies on β-cell function and β-cell mass in animals and humans.

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  • Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
    Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
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The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea
Seungjoon Oh, Suk Chon, Kyu Jeong Ahn, In-Kyung Jeong, Byung-Joon Kim, Jun Goo Kang
Diabetes Metab J. 2015;39(3):177-187.   Published online June 15, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.3.177
  • 5,118 View
  • 50 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce glycosylated hemoglobin (HbA1c, 0.5% to 1.0%), and are associated with moderate weight loss and a relatively low risk of hypoglycemia. There are differences between Asian and non-Asian populations. We reviewed available data on GLP-1RAs, focusing on Korean patients, to better understand their risk/benefit profile and help inform local clinical practice. Control of postprandial hyperglycemia is important in Asians in whom the prevalence of post-challenge hyperglycemia is higher (vs. non-Asians). The weight lowering effects of GLP-1RAs are becoming more salient as the prevalence of overweight and obesity among Korean patients increases. The higher rate of gastrointestinal adverse events amongst Asian patients in clinical trials may be caused by higher drug exposure due to the lower body mass index of the participants (vs. non-Asian studies). Data on the durability of weight loss, clinically important health outcomes, safety and optimal dosing in Korean patients are lacking. Use of GLP-1RAs is appropriate in several patient groups, including patients whose HbA1c is uncontrolled, especially if this is due to postprandial glucose excursions and patients who are overweight or obese due to dietary problems (e.g., appetite control). The potential for gastrointestinal adverse events should be explained to patients at treatment initiation to facilitate the promotion of better compliance.

Citations

Citations to this article as recorded by  
  • Safety and Effectiveness of Dulaglutide in the Treatment of Type 2 Diabetes Mellitus: A Korean Real-World Post-Marketing Study
    Jeonghee Han, Woo Je Lee, Kyu Yeon Hur, Jae Hyoung Cho, Byung Wan Lee, Cheol-Young Park
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  • Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
    Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
    Diabetes & Metabolism Journal.2017; 41(5): 337.     CrossRef
  • Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
    Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
    The Korean Journal of Internal Medicine.2017; 32(6): 947.     CrossRef

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