Association of glucagon-like peptide-1 receptor agonists with risk of cancers - evidence from a drug target

Q: Why was the study conducted on GLP1R agonists and cancer risk?

GLP1R agonists are approved for obesity, but the causal relationship between GLP1R agonists and cancers remained unclear. The study aims to clarify this using genetic and trial-based evidence.

Q: What methods were used to evaluate the association with cancers?

The study used drug-target cis-eQTLs as proxies for GLP1RA exposure and performed Mendelian randomization for 14 common cancer types. It also replicated results in FinnGen, pooled them with meta-analysis, and systematically searched randomized controlled trials to synthesize evidence.

Q: What were the main cancer risk findings for GLP1RA?

The evidence supported reduced breast cancer and basal cell carcinoma risk, and increased colorectal cancer risk. The study reported no suggestive evidence for ovarian, lung, or thyroid cancer associations.

Sep 21, 2026

Uploaded by Ezra

Glucagon-like peptide-1 receptor agonists (GLP1RA), approved for obesity management, raise uncertainty about their causal relationship with cancers. This study uses cis-eQTLs for the GLP1R target as proxies and applies Mendelian randomization to assess genetically proxied exposure with 14 cancer types from large consortia. Findings are replicated in FinnGen and combined via meta-analysis, then validated through a systematic search of randomized controlled trials (PubMed, Embase, Cochrane). Results indicate reduced breast cancer and basal cell carcinoma risk, increased colorectal cancer risk, and a low incidence overall in RCTs.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Background

Methods

Results

Conclusions

Key words

Introduction

’Experimental Research Association of glucagon-like peptide-1 receptor agonists with risk of cancers-evidence from a drug target Mendelian randomization and clinical trials Yuming Sun, PhDa,e , Yongjia Liu, MDf, Yating Dian, MDc,d , Furong Zeng, PhDb,* , Guangtong Deng, PhDc,d,* , Shaorong Lei, PhDa,* Background: Glucagon-like peptide-1 receptor (GLP1R) agonists have been approved by Food and Drug Administration for management of obesity. However, the causal relationship of GLP1R agonists (GLP1RA) with cancers still unclear. Methods: The available cis-eQTLs for drugs target genes (GLP1R) were used as proxies for exposure to GLP1RA. Mendelian randomizations (MR) were performed to reveal the association of genetically-proxied GLP1RA with 14 common types cancer from large-scale consortia. Type 2 diabetes was used as positive control, and the GWASs data including 80 154 cases and 853 816 controls. Replicating the ﬁndings in the FinnGen study and then pooled with meta-analysis. Finally, all the related randomized controlled trails (RCTs) on GLP1RA were systematically searched from PubMed, Embase, and the Cochrane Library to comprehensively synthesize the evidence to validate any possible association with cancers. Result: A total of 22 signiﬁcant cis-eQTL single-nucleotide polymorphisms were included as genetic instrument. The association of genetically-proxied GLP1RA with signiﬁcantly decreased type 2 diabetes risk [OR (95%) = 0.82 (0 .79–0.86), P < 0.001], which ensuring the effectiveness of identiﬁed genetic instruments. The authors found favorable evidence to support the association of GLP1RA with reduced breast cancer and basal cell carcinoma risk [0 .92 (0 .88–0.96), P < 0.001, 0 .92 (0 .85–0.99), P = 0.029, respectively], and with increased colorectal cancer risk [1 . 12 (1 .07–1. 18), P < 0.001] . In addition, there was no suggestive evidence to support the association of GLP1RA with ovarian cancer [0 .99 (0 .90–1.09), P = 0.827], lung cancer [1 .01 (0 .93–1. 10), P = 0760], and thyroid cancer [0 .83 (0 .63–1. 10), P = 0. 187] . Our ﬁndings were consistent with the meta-analysis. Finally, 80 RCTs were included in the systematic review, with a low incidence of different kinds of cancer. Conclusions: Our study suggests that GLP1RA may decrease the risk of breast cancer and basal cell carcinoma, but increase the risk of colorectal cancer. However, according to the systematic review of RCTs, the incidence of cancer in patients treated with GLP1RA is low. Larger sample sizes of RCTs with long-term follow-up are necessary to establish the incidence of cancers and evaluate the risk-beneﬁt ratios. Key words: cancers, drug target, GLP1R agonists, Mendelian randomization Introduction Semaglutide, an agonist of glucagon-like peptide-1 receptor (GLP1R), was originally developed for the treatment of type 2 diabetes, and has been granted supplemental approved by the U.S. Food and Drug Administration (FDA) on 4 June 2021 for use in obese and overweight adult[1] . GLP1R is expressed in various tissues and organs, including the adipose, smooth muscle, lungs heart, kidney and pancreas, and speciﬁc nuclei of the central nervous system[2] . Glucagon-like peptide-1 receptor agonists aDepartment of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, bDepartment of Oncology, Xiangya Hospital, Central South University, cDepartment of Dermatology, Xiangya Hospital, Central South University, dHunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, eNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan and fDepartment of Orthopedics, The 82nd Group Army Hospital of PLA (252 Hospital of PLA), Baoding, People’s Republic of China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corre

FAQs

Why was the study conducted on GLP1R agonists and cancer risk?

GLP1R agonists are approved for obesity, but the causal relationship between GLP1R agonists and cancers remained unclear. The study aims to clarify this using genetic and trial-based evidence.

What methods were used to evaluate the association with cancers?

The study used drug-target cis-eQTLs as proxies for GLP1RA exposure and performed Mendelian randomization for 14 common cancer types. It also replicated results in FinnGen, pooled them with meta-analysis, and systematically searched randomized controlled trials to synthesize evidence.

What were the main cancer risk findings for GLP1RA?

The evidence supported reduced breast cancer and basal cell carcinoma risk, and increased colorectal cancer risk. The study reported no suggestive evidence for ovarian, lung, or thyroid cancer associations.

Sep 21, 2026

Uploaded by Ezra