Use of Antihyperglycemic Drugs and Risk of Cancer in Patients with Diabetes

Purpose of Review Diabetes is associated with an increased risk for several types of cancer. Therefore, use of antihyperglycemic medications to lower blood glucose may modify cancer risk. Here we review available data on the link between the most common classes of antihyperglycemic agents and cancer risk among patients with diabetes. Recent Findings A database search was conducted between February 2022 and June 2022 on PubMed and Embase for systematic reviews and meta-analyses investigating the association between antihyperglycemic agents and risk of cancer. Use of biguanides such as metformin is associated with 20-30% lower risk for all cancer incidence, and somewhat greater benefit for cancer-related mortality. Alpha-glucosidase inhibitors, e.g., acarbose, have not been consistently associated with cancer. Similarly, no consistent effects have been reported for thiazolidinediones, but the relationship with cancer seems to depend on the type of drug, dose, and duration of treatment. Exposure to various types of incretin-based therapies (glucagon-like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors) has not been found to significantly modify cancer risk. Inhibitors of sodium glucose cotransporter-2 may raise risk for bladder cancer and reduce risk for gastrointestinal cancer. Use of insulin and insulin analogs is associated with a significant increase in total cancer risk by almost 50% compared to other antihyperglycemic drugs. Likewise, insulin secretagogues like sulfonylureas have generally been linked to greater risk for cancer by similar to 20%, although these associations may be agent-specific and dose-dependent. Current evidence suggests that the risk of cancer associated with the use of antihyperglycemic medications among patients with diabetes depends on the class of drug and type of agent, dosage, and duration of treatment. More research is needed to delineate the mechanisms by which these agents affect the process of carcinogenesis.