GLP-1 receptor agonists and risk of cancer in type 2 diabetes: an updated meta-analysis of randomized controlled trials
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META-ANALYSIS
GLP-1 receptor agonists and risk of cancer in type 2 diabetes: an updated meta-analysis of randomized controlled trials Chuqing Cao1,2 Shuting Yang1,2 Zhiguang Zhou ●
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Received: 5 July 2019 / Accepted: 6 August 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Purpose Some preliminary studies reported a link between GLP-1 receptor agonists (GLP-1RAs) and thyroid/pancreatic neoplasms, while its human relevance remained undetermined. The present meta-analysis was performed to collect information on cancers associated with GLP-1RAs in patients with type 2 diabetes mellitus (T2DM). Methods Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and ClinicalTrials.gov were extensively searched to identify randomized controlled trials that reported cancer events in T2DM patients treated with GLP-1RAs for at least 52 weeks, up to March 18, 2019. Odds ratio (OR) with 95% Confidence Interval (CI) was calculated for overall cancer (primary outcome), thyroid and pancreatic cancer. Results A total of 37 eligible trials were identified. The OR for overall cancer associated with GLP-1RAs was 1.03 (95% CI 0.95–1.12; p = 0.41) compared with comparators. Subgroup analyses showed that treatment with albiglutide was associated with a lower risk of overall cancer (OR 0.76 [95% CI 0.60–0.97]; p = 0.03), and no elevated risk of overall cancer was identified for other GLP-1RAs. No significant differences in the risks of thyroid nor pancreatic cancer were disclosed between GLP-1RAs and comparators. Conclusions This meta-analysis did not suggest any increased risk of cancers associated with GLP-1RAs use in T2DM. The reduction in the risk of overall cancer associated with albiglutide needs to be examined further. Keywords GLP-1 receptor agonists Cancer Meta-analysis Type 2 diabetes mellitus Randomized controlled trials ●
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Introduction Growing evidence suggests the association of type 2 diabetes mellitus (T2DM) and an increased risk of cancer [1]. Although the underlying mechanisms are not fully understood, potential mechanisms involve overproduction of reactive oxygen species, insulin and insulin-like growth factor receptor-1 [2]. On the other hand, hyperglycemia and
Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-019-02055-z) contains supplementary material, which is available to authorized users. * Zhiguang Zhou [email protected] 1
Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, No. 139 Renmin Road, Changsha 410011 Hunan, China
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Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, China
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concurrent obesity also impair immunosurveillance and blunt antitumor responses [3]. Currently multiple classes of antidiabetic agents are available for the treatment of T2DM, and it is critical that antidiabetic drugs
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