Dipeptidyl peptidase-4 inhibitors and risk of multiple sclerosis: A Danish nationwide matched case-control study.

BACKGROUND: Treatment with dipeptidyl peptidase-4 inhibitors (DPP-4i) is a strong risk factor for developing bullous pemphigoid, a dermatological disorder that is itself strongly associated with multiple sclerosis (MS). We therefore hypothesized that DPP-4i would also increase the risk of MS. OBJECTIVE: To investigate whether prior use of DPP-4i is associated with incident MS. METHODS: This nationwide register-based matched case-control study included individuals with incident MS identified by date of diagnosis (index date) in the Danish Multiple Sclerosis Registry between 2008 and 2023 matched 1:10 with population controls based on year of birth, gender, place of residence, and index date. Exposure was classified as a three-level mutually exclusive variable based on redeemed prescriptions at any time before the index date: any DPP-4i use, other type 2 diabetes medication use, or non-use. Conditional logistic regression was used to estimate odds ratios with 95% confidence intervals. RESULTS: A total of 9063 incident cases of MS and 90,630 controls were identified. The mean age at the index date was 41.36 years for patients with MS and 41.48 years for controls. Prior DPP-4i exposure was observed in 27 MS cases (0.30%) and 405 controls (0.45%), corresponding to an odds ratio of 0.67 (95% CI, 0.45-0.99) versus non-use. Other type 2 diabetes medication use was observed in 274 MS cases (3.02%) and 2474 controls (2.73%), corresponding to an odds ratio of 1.11 (95% CI, 0.98-1.26) versus non-use. CONCLUSION: DPP-4i use was not associated with an increased risk of MS and may be protective.