OBJECTIVES: Current literature lacks conclusive evidence regarding the potential risk or protective effects on cancer associated with novel antidiabetic medications. Based on real-world evidence, this systematic review and network meta-analysis aims to compare the potential cancer risks or protective effects associated with these novel antidiabetic medications.

METHODS: We systematically searched PubMed, CINAHL, and Web of Science until November 2023. For the systematic review, we included observational studies that involved at least one class of novel antidiabetic medications (sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1) agonists) in the intervention arm. For the network meta-analysis (NMA), we limited our selection to cohort studies that reported cancer incidence and sample size. A random-effects model with informative priors was used in the NMA to estimate the pooled odds ratio (OR) with 95% credible intervals (CI) based on the Bayesian framework using NetMetaXL®.

RESULTS: Out of the 62 studies (53 cohorts and 9 case-control) in our systematic review, 22 studies were included in the NMA. SGLT-2 inhibitors were likely to reduce the overall cancer risk compared to sulfonylureas (OR:0.54; 95%CI: 0.40 – 0.74), GLP-1 agonists (OR:0.70; 95%CI: 0.53 – 0.92), and DPP-4 inhibitors (OR:0.72; 95%CI: 0.57 – 0.92). DPP-4 inhibitors were also associated with a lower risk of cancer compared to sulfonylureas (OR:0.76; 95%CI: 0.60 – 0.96). No statistically significant odds ratios were observed in other head-to-head comparisons in our NMA.

CONCLUSIONS: SGLT-2 inhibitors are associated with protective effects against developing cancer compared to sulfonylureas, GLP-1 agonists, and DPP-4 inhibitors. These results may influence clinical practice by guiding medication choices with a focus on patient safety. Further studies are needed to explore the mechanisms behind this observed association.