OBJECTIVES: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used across the globe to control sugar levels in adults with Type 2 diabetes mellitus. Specific cancer types have been found to be associated with DPP-4 inhibitors in the literature, such as pancreatic cancer. To date, very few studies have comprehensively evaluated the association between DPP-4 inhibitors and all other types of cancers. The objective of this study was to comprehensively evaluate the overall cancer and specific cancer types associations with DPP-4 inhibitors using the FDA Adverse Event Reporting System (FAERS).

METHODS: FAERS reports from January 1, 2004 to September 30, 2022 were included in the study. Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between DPP-4 inhibitors and cancer were calculated. An association was considered to be statistically significant when the lower limit of the 95%CI was greater than 1.

RESULTS: A total of 15,598,679 reports were considered, after inclusion criteria were applied. Overall cancer RORs (95% CI) for DPP-4 inhibitors were (in descending order): alogliptin 1.52 (1.37-1.69), sitagliptin 1.35 (1.32-1.39), saxagliptin 0.97 (0.89-1.05), and linagliptin 0.83 (0.78-0.89). Pancreatic cancer RORs (95% CI) for DPP-4 inhibitors were (in descending order): sitagliptin 19.35 (18.63-20.09), saxagliptin 7.48 (6.40-8.74), alogliptin 6.39 (4.92-8.30), and linagliptin 4.01 (3.45-4.66). Bladder cancer RORs (95% CI) for DPP-4 inhibitors were (in descending order): sitagliptin 3.32 (3.12-3.53), saxagliptin 2.29 (1.86-2.82), alogliptin 1.99 (1.41-2.82), and linagliptin 0.84 (0.65-1.07). Liver cancer RORs (95% CI) for DPP-4 inhibitors were (in descending order): alogliptin 3.17 (2.23-4.51), linagliptin 1.54 (1.22-1.94), saxagliptin 1.01 (0.67-1.50), sitagliptin 0.98 (0.85-1.13).

CONCLUSIONS: In FAERS, alogliptin and sitagliptin were significantly associated with overall cancer. Sitagliptin, saxagliptin, alogliptin, and linagliptin were significantly associated with pancreatic cancer. Sitagliptin, saxagliptin, and alogliptin were significantly associated with bladder cancer. Alogliptin and linagliptin were significantly associated with liver cancer.