Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the management of obesity and type 2 diabetes, including among patients with cancer. Although previous research has mainly focused on cancer incidence, their associations with clinical outcomes after cancer diagnosis remain less well characterized. Therefore, the present study aimed to evaluate the oncologic and survival outcomes associated with GLP-1 RA use in adults with an established malignancy. We performed a systematic review of comparative studies evaluating GLP-1 RA use in patients with a confirmed cancer diagnosis. PubMed, Scopus and Web of Science were searched for English-language publications from 1 January 2016 to 8 August 2026. Twenty-six retrospective cohort studies were included in the qualitative synthesis. Thirteen studies included selective GLP-1 RAs and tirzepatide within the same exposure group. Study quality was assessed using the Newcastle-Ottawa Scale. Twenty-five studies evaluated overall survival and/or all-cause mortality, while nine assessed cancer recurrence, progression, or related outcomes. Survival and mortality outcomes more often favored the exposed group (especially compared with nonuse) than not, but findings were less consistent in active-comparator analyses. Evidence for recurrence and progression was sparse and heterogeneous, and no clear signal of increased risk was observed. Because all of these were observational studies with substantial differences in populations, comparators, exposure definitions, and duration of follow-up, the survival associations do not imply causality or direct antitumor effects of GLP-1 RAs. Clinically, the preponderance of evidence does not support the use of GLP-1 RAs as cancer-directed therapy, and their use in patients with cancer should be guided by established indications such as obesity and type 2 diabetes. Potential explanations include effects on glycemic and cardiovascular risk factors, treatment selection, residual confounding, or combinations thereof. Prospective studies and randomized controlled trials with cancer-specific outcomes and longer follow-up are needed to further evaluate these associations.
