Epidemiologic data have demonstrated significant increases of various cancers in people with obesity and dia-betes. Recently, concern has emerged that antihyperglyce-mic medications may also be associated with an increased prevalence of multiple cancers; however, available data are limited and conflicting. The American Association of Clinical Endocrinologists (AACE) convened a confer-ence to review factors associated with cancer develop-ment in people with obesity and diabetes and to discuss the possible cancer risk of antihyperglycemic medications. Increased body mass index is associated with an increased risk of multiple cancers based on observational epidemio-logical data, and is closely associated with increased levels of endogenous insulin, insulin-like growth factors, inflam-matory cytokines, and other factors that can have down-stream pro-cancer growth effects.
The role of hyperglycemia in cancer development is less clear, but an association cannot be ruled out, as current observational data additionally suggest an increased can-cer risk in people with diabetes. There is currently insuffi-cient evidence that antihyperglycemic medications may be definitively associated with an increased cancer risk owing to a lack of data from large-scale randomized study designs. Similarly, there is also insufficient evidence showing a pos-itive impact of these medications on cancer development. Clinicians can continue to confidently prescribe all FDA-approved antihyperglycemic medications for the manage-ment of hyperglycemia according to established practice guidelines. In patients who have an elevated cancer risk or positive family history of cancer, the cautious selection of antihyperglycemic medications is both prudent and war-ranted. The AACE additionally advocates for the improved treatment and management of obesity, early cancer screen-ing in patients at increased risk, increased research collabo-ration, and improved study designs to address outstanding concerns surrounding the diabetes-cancer relationship.Abbreviations:AACE = American Association of Clinical Endocrinologists; BMI = body mass index; CI = confi-dence interval; DPP-4 = dipeptidyl peptidase-4; EMA = European Medicines Agency; FDA = U.S. Food and Drug Administration; GLP-1 = glucagon-like pep-tide-1; HR = hazard ratio; IGF = insulin-like growth factor; IGFBP = insulin-like growth factor binding pro-tein; IR = insulin receptor; RR = relative risk; T2D = type 2 diabetes; TZD = thiazolidinedioneINTRODUCTION A conference and writing task force was commissioned by the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology to determine the possible roles of obesity, hyperinsulinism, glucose, and diabetes and its therapies in the pathogenesis of cancer. The purpose of this document is to review the available evidence, provide recommendations to practicing clinicians, and highlight research needs.POSITION STATEMENT PDF