Dipeptidyl peptidase-4 inhibitors and the risk of skin cancer among patients with type 2 diabetes: a UK population-based cohort study

Abstract

IntroductionThe dipeptidyl peptidase-4 (DPP-4) enzyme significantly influences carcinogenic pathways in the skin. The objective of this study was to determine whether DPP-4 inhibitors are associated with the incidence of melanoma and nonmelanoma skin cancer, compared with sulfonylureas.Research design and methodsUsing the United Kingdom Clinical Practice Research Datalink, we assembled two new-user active comparator cohorts for each skin cancer outcome from 2007 to 2019. For melanoma, the cohort included 96 739 DPP-4 inhibitor users and 209 341 sulfonylurea users, and 96 411 DPP-4 inhibitor users and 208 626 sulfonylurea users for non-melanoma skin cancer. Propensity score fine stratification weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs of melanoma and non-melanoma skin cancer, separately.ResultsOverall, DPP-4 inhibitors were associated with a 23% decreased risk of melanoma compared with sulfonylureas (49.7 vs 65.3 per 100 000 person-years, respectively; HR 0.77, 95% CI 0.61 to 0.96). The HR progressively reduced with increasing cumulative duration of use (0–2 years HR 1.14, 95% CI 0.84 to 1.54; 2.1–5 years HR 0.44, 95% CI 0.29 to 0.66; >5 years HR 0.33, 95% CI 0.14 to 0.74). In contrast, these drugs were not associated with the incidence of non-melanoma skin cancer, compared with sulfonylureas (448.1 vs 426.1 per 100 000 person-years, respectively; HR 1.06, 95% CI 0.98 to 1.15).ConclusionsIn this large, population-based cohort study, DPP-4 inhibitors were associated with a reduced risk of melanoma but not non-melanoma skin cancer, compared with sulfonylureas.

The Analysis Study of Association of Type 2 Diabetes Mellitus and Skin Cancer : A Comprehensive Systematic Review

“…However, these drugs were not associated with non-melanoma skin cancer. 17 The DPP-4 enzyme plays a complex role in the malignant transformation of melanocytes, and biological findings in murine models explain its possible benefits in melanoma. 22 The study found no consistent association between DPP-4 inhibitor use and non-melanoma skin cancer.…”

“…23 More research is needed to confirm these findings, given the high mortality associated with melanoma and the lack of preventive strategies related to this malignancy. 17 According to a recent study, people with type 2 diabetes who take GLP-1 RAs, like liraglutide, do not have a higher risk of developing skin cancer. This is the first population-based cohort study to evaluate the relationship between GLP-1 RAs and the incidence of skin cancer.…”