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Cited by 67Diabetes Treatment and ManagementMetabolism, Diabetes, and CancerPharmacology and Obesity Treatment

GLP ‐1 receptor agonists and the risk for cancer: A meta‐analysis of randomized controlled trials

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Silverii, Giovanni Antonio, Marinelli, Christian, Bettarini, Costanza, Del Vescovo, Gloria Giovanna, Monami, Matteo, Mannucci, Edoardo·2025·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.16489PMC PMC12232360
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Abstract

Aims: To assess if there is a difference in the oncogenic risk between GLP‐1 RA and comparators in randomized controlled trials. Materials and Methods: A meta‐analysis of randomized controlled trials comparing GLP‐1RA to any comparators for diabetes and/or obesity, lasting at least 52 weeks. The endpoints included the incidence of overall cancers and single malignancies. Results: Fifty trials were included. GLP‐1RA treatment was not associated with a significant difference in risk for overall cancer (MH‐OR 1.05, 95% confidence interval [CI] [0.98, 1.13]). Uterine cancer was significantly reduced in the GLP‐1RA arm in trials performed in subjects with obesity (MH‐OR 0.24, 95% CI [0.06, 0.94]), but not in those aimed at diabetes treatment (MH‐OR 0.92, [0.58, 1.47]). We detected an increase in the risk for thyroid cancer (MH‐OR 1.55, [1.05, 2.27]), more evident in longer‐term trials, and in the risk for colorectal cancer (MH‐OR 1.27 [1.03, 1.57]), which, conversely, was significant only in shorter‐term trials. No significant difference in the risk was detected for any other cancer. Conclusions: GLP‐1 RA do not appear to produce an effect on most malignancies in clinical trials. A reduction of very close obesity‐associated cancers seems possible, whereas a risk signal for thyroid cancer was observed, prompting the need for further specific studies. On the other hand, the small increase observed in colorectal cancer in shorter‐term trials may be the effect of a disproportionate increase in diagnostic procedures in the GLP‐1 RA arm, because of the suspicion raised by common side effects of GLP‐1 RA.

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  • A small increase in colorectal cancer was detected in short-term trials (MH-OR 1.27, 95% CI 1.03-1.57), potentially due to increased diagnostic procedures prompted by GLP-1 RA gastrointestinal side effects.

    “However, a small increase in colorectal cancer was detected in short-term trials (MH-OR 1.27, 95% CI 1.03–1.57), potentially due to increased diagnostic procedures prompted by GLP-1 RA gastrointestinal side effects.”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [145]

    The Results (Incidence of obesity-associated cancers; page not provided) give MH-OR 1.27 [1.03, 1.57] for colorectal cancer across the trials, but MH-OR 2.28 [1.04, 4.98] for shorter trials specifically. The Discussion supports the proposed explanation involving diagnostic procedures prompted by gastrointestinal side effects, but presents it as speculation. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • A 2025 meta-analysis by Silverii et al. that pooled 50 randomized trials found GLP-1 RA were associated with a modest but significant increase in thyroid cancer risk (MH-OR 1.55, 95% CI 1.05-2.27), particularly in longer-duration studies.

    “A 2025 meta-analysis by Silverii et al. that pooled 50 randomized trials, GLP-1 RA were associated with a modest but significant increase in thyroid cancer risk (MH-OR 1.55, 95% CI 1.05–2.27), particularly in longer-duration studies.”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [145]

  • GLP-1 RA were not associated with an overall increased cancer risk (MH-OR 1.05, 95% CI 0.98-1.13).

    “GLP-1 RA were not associated with an overall increased cancer risk (MH-OR 1.05, 95% CI 0.98–1.13).”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [145]

  • A significant reduction in uterine cancer was noted in obesity-focused trials (MH-OR 0.24, 95% CI 0.06-0.94), but not in diabetes trials.

    “A significant reduction in uterine cancer was noted in obesity-focused trials (MH-OR 0.24, 95% CI 0.06–0.94), but not in diabetes trials [145].”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [145]

  • In that meta-analysis, no other cancer types showed significant associations with GLP-1 RA.

    “No other cancer types showed significant associations [145].”

    From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [145]

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Sorted by citations

Authors
Silverii, G. A., Marinelli, C., Bettarini, C., Del Vescovo, G. G., Monami, M., & Mannucci, E.
Affiliations
  • Azienda Ospedaliero-Universitaria Careggi (IT)
  • AOU Careggi, Diabetology Unit – Experimental and Clinical Biomedical Sciences “Mario Serio” Department University of Florence Florence Italy
Corresponding author
Silverii, Giovanni Antonio
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2025-05-29
Volume
27
Issue
8
Pages
4454-4468
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.16489
PMC
PMC12232360
OpenAlex
W4410839583
Cited by
67
References
35
Citations by year
2026: 54 · 2025: 13
FWCI
9.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Obesity and Metabolism (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Florence Research (University of Florence) (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Keywords
GLP-1 receptor agonists, cancer risk, thyroid cancer, colorectal cancer, uterine cancer, obesity, type 2 diabetes, adverse drug reactions, cancer incidence
MeSH terms
Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Neoplasms, Obesity, Risk Factors, Colorectal Neoplasms, Incidence, Randomized Controlled Trials as Topic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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