Dipeptidyl peptidase-4 inhibitors may be associated with an increased incidence of malignancy

1. Sitagliptin demonstrated the most prominent malignancy-related safety signal among the dipeptidyl peptidase-4 inhibitors studied.

Evidence Rating Level: 2 (Good) 

Dipeptidyl peptidase-4 inhibitors are widely used for type 2 diabetes because they have a low risk of severe hypoglycemia and are weight neutral, but their relationship with malignancy remains uncertain. This study used the FDA Adverse Event Reporting System from January 2019 through December 2024 to assess malignancy-related adverse event signals among patients with type 2 diabetes receiving sitagliptin, saxagliptin, linagliptin, alogliptin, or vildagliptin. The authors performed descriptive analyses, disproportionality testing using reporting odds ratios and information components, and adjusted logistic regression to account for age, sex, and selected concomitant medications. They identified 3,764 malignancy-related reports. Sitagliptin showed the strongest and broadest signal across both standardized query groupings and preferred terms. After adjustment, positive associations persisted for sitagliptin, vildagliptin, and linagliptin, whereas saxagliptin was not statistically significant, and alogliptin showed an inverse association. Most reported events occurred in older adults, with median ages above 70 years in most groups. In drugs with larger sample sizes, the median time to event onset was approximately 13 to 15 months. The authors conclude that these findings represent pharmacovigilance signals rather than proof of causation, but they support closer surveillance and the need for large prospective studies to determine whether these associations reflect true cancer risk.

Click here to read this study in PLOS One

Image: PD

©2026 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.