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Meta-Analysis
. 2025 Aug;27(8):4454-4468.
doi: 10.1111/dom.16489. Epub 2025 May 29.

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

Giovanni Antonio Silverii  1 , Christian Marinelli  1 , Costanza Bettarini  1 , Gloria Giovanna Del Vescovo  1 , Matteo Monami  2 , Edoardo Mannucci  1
Affiliations
Meta-Analysis

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

Giovanni Antonio Silverii et al. Diabetes Obes Metab. 2025 Aug.

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.

Keywords: GLP‐1 RA; cancer; dulaglutide; exenatide; glucagon‐like peptide‐1 receptor agonists; liraglutide; meta‐analysis; obesity; semaglutide; type 2 diabetes mellitus.

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Conflict of interest statement

GAS has received speaking or consultancy fees from Astra Zeneca, Eli‐Lilly and Novo Nordisk, outside the submitted work. MM has received speaking fees from Astra Zeneca, Boehringer‐Ingelheim, Eli‐Lilly, Merck, Novo Nordisk and Sanofi, outside the submitted work. The unit directed by EM has received research grants from Abbott, Eli‐Lilly and Novo Nordisk, outside the submitted work. EM has received consultancy fees or speaking fees from Astra Zeneca, Bayer, Boehringer‐Ingelheim, Coresearch, Dexcom, Eli‐Lilly, Molteni, Novo Nordisk, Pidkare and Sanofi, outside the submitted work. C.M., G.G.D.V. and C.B. do not have any competing interests to disclose.

Figures

FIGURE 1
FIGURE 1
Difference in risk for any cancer between patients on GLP‐1RA and patients on comparators (forest plot). CI, confidence interval; M‐H, Mantel‐Haenzel.
FIGURE 2
FIGURE 2
Difference in risk for any cancer between patients on GLP‐1RA and patients on comparators (forest plot); subgroup analysis between trials lasting 52 weeks, trials lasting more than 53 but less than 103 weeks, and trials lasting 104 weeks or more. CI, confidence interval; M‐H, Mantel‐Haenzel.
FIGURE 3
FIGURE 3
Difference in risk for endometrial cancer between patients on GLP‐1RA and patients on comparators (forest plot); subgroup analysis between trials. CI, confidence interval; M‐H, Mantel‐Haenzel.
FIGURE 4
FIGURE 4
Difference in risk for each other specific cancer between patients on GLP‐1RA and patients on comparators (forest plot); CI, confidence interval; OR, odds ratio; please note that “Lymphocyte Malignancies” encompasses both Lymphomas and Chronic Lymphatic Leukaemia.
See this image and copyright information in PMC

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