EvidenceAlerts

Silverii GA, Marinelli C, Bettarini C, et al. GLP-1 receptor agonists and the risk for cancer: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2025 May 29. doi: 10.1111/dom.16489. (Systematic review)
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.

Ratings
Discipline Area Score
Endocrine 7 / 7
Special Interest - Obesity -- Physician 6 / 7
Family Medicine (FM)/General Practice (GP) 5 / 7
General Internal Medicine-Primary Care(US) 5 / 7
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

Important to revew side effects in new promising drugs. In RCTs available to date, GLP-1RA do not appear to produce major effects on most malignancies, either beneficial or detrimental.

Special Interest - Obesity -- Physician rater

Informative analysis of the cancer profile of these medications.
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