Association between antidiabetic drugs and cancer risk in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis

BACKGROUND Current evidence suggests that commonly used antidiabetic drugs have varying effects on cancer risk. Some antidiabetics offer protective effects against cancer, whereas others may increase risk in specific populations. AIM To comprehensively compare the effects of different antidiabetic drugs on the risk of various cancers in patients with type 2 diabetes mellitus (T2DM) through a systematic review and network meta-analysis. METHODS Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from their inception until April 11, 2025. Published randomized controlled trials that enrolled at least 100 participants and had an intervention duration of at least 1 year were included. The inclusion criteria were studies involving adult patients with T2DM and interventions that compared different classes of antidiabetic drugs with a placebo or another antidiabetic drug. Network meta-analysis was conducted using Stata 17.0 software. Confidence in network meta-analysis was used to assess the quality of evidence regarding the risk of cancer associated with different antidiabetic drugs. RESULTS A total of 13535 articles were identified. After applying the inclusion and exclusion criteria, 87 high-quality studies involving 216106 patients and 26 different drugs across seven classes were included in this study. Indirect evidence from network meta-analysis revealed some heterogeneity; however, this did not affect the reliability of the results. The results indicated that antidiabetic drugs did not increase the overall risk of cancer compared with placebo. In contrast, some antidiabetic medications demonstrated a more pronounced advantage in reducing cancer risk, such as dipeptidyl peptidase-4 inhibitors for thyroid and rectal cancers; sodium-glucose co-transporter type 2 inhibitors for lung and bronchial cancers; sulfonylureas for gastric and colon cancers; biguanides for pancreatic cancer; insulin for bladder cancer; glucagon-like peptide-1 receptor agonists for prostate, uterine, hepatocellular, renal, and hematologic cancers; and thiazolidinediones for breast cancer. CONCLUSION Antidiabetic drugs reduce cancer risk in patients with T2DM. However, given the limitations in the number and quality of the included studies, our conclusions should be interpreted with caution. More large-scale, high-quality clinical trials are required to validate our findings towards the optimization of comprehensive cancer management strategies for patients with T2DM.