Diabetes & Metabolism Journal

Original Article

Drug/Regimen
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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Abstract PDF Supplementary Material PubReader ePub: 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

Hyperglycemia as a Risk Factor for Cancer Progression: Tae Young Ryu, Jiyoung Park, Philipp E. Scherer; Diabetes Metab J. 2014;38(5):330-336. Published online October 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.5.330

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As the prevalence of diabetes mellitus is substantially increasing worldwide, associated diseases such as renal failure, cardiovascular diseases, fatty liver, and cancers have also increased. A number of cancers such as pancreatic, liver, breast, and female reproductive cancers have shown an increased prevalence and a higher mortality rate in diabetic patients compared to healthy subjects. Thus, this suggests an association between diabetes, especially type 2 diabetes and cancer incidence and progression. Recent studies have suggested that hyperinsulinemia, chronic inflammation and hyperglycemia, all frequently seen in diabetics, may lead to increased tumor growth; the underlying molecular mechanisms of this association are not fully understood. In particular, chronic hyperglycemic episodes could serve as a direct or indirect mediator of the increase in tumor cell growth. Here, we will discuss our current understanding how hyperglycemia and cancer risk may be linked, and what the implications are for the treatment of diabetic cancer patients.

Citations

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Diabetes and Cancer: Is Diabetes Causally Related to Cancer?: Sunghwan Suh, Kwang-Won Kim; Diabetes Metab J. 2011;35(3):193-198. Published online June 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.3.193

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Diabetes mellitus is a serious and growing health problem worldwide and is associated with severe acute and chronic complications. Moreover, epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer. Several studies indicate an association between diabetes and the risk of liver, pancreas, endometrium, colon/rectum, breast, and bladder cancer. Mortality is also moderately increased in subjects with diabetes. Common risk factors such as age, obesity, physical inactivity and smoking may contribute to increased cancer risk in diabetic patients. Hyperinsulinemia most likely favors cancer in diabetic patients as insulin is a growth factor with pre-eminent metabolic as well as mitogenic effects, and its action in malignant cells is favored by mechanisms acting at both the receptor and post-receptor level. The effect of diabetes treatment drugs, aside from metformin, on cancer is not conclusive. In order to fight the perfect storm of diabetes and cancer, strategies to promote primary prevention and early detection of these conditions are urgently needed.

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Original Article

Prevalence of Diabetes Mellitus in Pancreatic Cancer Patients.: Yu Jeong Park, Kwang Won Kim, Eun Young Oh, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Jong Kyun Lee, Kyu Taek Lee, Yong Il Kim, Yoon Ho Choi; Korean Diabetes J. 2001;25(4):316-322. Published online August 1, 2001

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Abstract PDF: BACKGROUND
Pancreatic cancer is a highly malignant tumor and its incidence has been significantly increased. It has well been known that pancreatic cancer patients had high prevalence of diabetes mellitus. But it is still controversial if diabetes predispose pancreatic cancer or it is an epiphenomenon of pancreatic cancer. Thus, the aims of this study was to investigate the prevalence of diabetes mellitus in pancreatic cancer patients in Korea, to characterize the diabetes mellitus in this situation, and to observe an association between the two conditions. METHOD: 275 pancreatic cancer patients admitted in Samsung Medical Center from January 1998 to December 2000 were selected for this study. We reviewed patients medical record and recorded diabetic history. Subjects who visited our Health Promotion Center in 1999 was used to evaluate the prevalence of diabetes mellitus. RESULT: 30% of pancreatic cancer patients had diabetes mellitus. 60% of diabetic pancreatic cancer patients had detected diabetes within recent two years. 25.6% of them had been known their diabetic state when they detected pancreatic cancer. There were no differences in smoking history, percent of distant metastasis, frequency of curative resection, and BMI between diabetic and nondiabetic pancreatic cancer patients. Significant weight loss was noted in pancreatic cancer patients with diabetes (p<0.01). CONCLUSION: The prevalence rate of diabetes in pancreatic cancer patient was significantly high. Pancreatic cancer patients with diabetes presented with much profound weight loss. Furthermore, more than half of the pancreatic cancer patients with diabetes had recent onset diabetes. Further investigations would be necessary to elucidate causal relation in the pathogenesis of diabetes and pancreatic cancer.

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