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

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.