GLP-1 receptor agonists show little effect on obesity-related cancer risk

1. In this systematic review and meta-analysis, use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) was not associated with a significant change in the risk of thyroid, pancreatic, breast, or kidney cancer.

2. Findings were consistent across subgroups, including by follow-up duration and among trials enrolling patients with type 2 diabetes, overweight or obesity, or both conditions.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The relationship between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and cancer risk remains uncertain. While some preclinical studies and clinical reports have raised concerns about a potential association with thyroid cancer, GLP-1RAs have also been hypothesized to reduce the risk of obesity-related malignancies. This systematic review and meta-analysis evaluated the risk of thyroid, pancreatic, and other obesity-related cancers among patients using GLP-1RAs or dual agonists. Patients receiving GLP-1RAs demonstrated a slightly increased likelihood of developing thyroid cancer; however, the absolute risk was very low. Rates of pancreatic, breast, and kidney cancer did not differ significantly between GLP-1RA users and placebo groups. Other cancers, including colorectal, esophageal, gallbladder, ovarian, endometrial, multiple myeloma, and meningioma, also showed no clear association with GLP-1RA use, although these findings were based on lower-certainty evidence. Subgroup analyses stratified by follow-up duration and by trial population (type 2 diabetes, overweight or obesity, or both) yielded consistent results, as did multiple sensitivity analyses. No significant evidence of publication bias was detected. The generalizability of these findings is limited by heterogeneity across trials and by the fact that the included studies were not designed primarily to assess cancer outcomes. Overall, this review suggests that GLP-1RAs do not meaningfully influence the risk of most obesity-related cancers. Nevertheless, longer-term studies specifically powered to evaluate cancer outcomes are needed to fully elucidate potential risks or benefits.

Click to read this study in AIM

Relevant Reading: GLP-1RA Use and Thyroid Cancer Risk

In-Depth [systematic review and meta-analysis]: This systematic review and meta-analysis evaluated the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the risk of thyroid, pancreatic, and other obesity-related cancers. We systematically searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (inception to August 15, 2025) for placebo-controlled randomized clinical trials assessing GLP-1RAs or dual agonists in adults with type 2 diabetes, overweight, or obesity that reported at least one cancer outcome. Trials of unapproved GLP-1RAs, without placebo comparators, or enrolling other populations were excluded. Of 12,960 articles screened, 48 trials were included, encompassing 94,245 participants (51,521 receiving GLP-1RAs/dual agonists; 42,724 receiving placebo). Twenty-six trials enrolled patients with type 2 diabetes, 18 with overweight or obesity, and 4 included both. Most studies (n = 43) were low risk of bias, with a median follow-up of 70 weeks. Thyroid cancer occurred in 0.14% of GLP-1RA users versus 0.07% of placebo recipients (odds ratio [OR], 1.37; 95% CI, 0.82 to 2.31), corresponding to roughly 1 fewer to 9 additional cases per 10,000 patients. Incidence of pancreatic, breast, and kidney cancers was similarly low and not significantly different: pancreatic cancer (OR, 0.84; 95% CI, 0.53 to 1.35), breast cancer (OR, 0.95; 95% CI, 0.60 to 1.49), kidney cancer (OR, 1.12; 95% CI, 0.78 to 1.60). No significant associations were observed for other cancers, including colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancers. Sensitivity analyses limited to low-bias studies or trials of semaglutide or tirzepatide did not change results. Subgroup analyses showed no meaningful differences by follow-up duration (≤104 vs >104 weeks) or study population (type 2 diabetes, overweight/obesity, or both). Gallbladder cancer showed a numerically higher risk in trials exceeding 104 weeks, though event counts were small. Overall, GLP-1RA therapy was not associated with a significant change in risk for thyroid, pancreatic, or other obesity-related cancers. Longer-term, cancer-focused studies are needed to confirm these findings and clarify any potential long-term risks.

Image: PD

©2025 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.