Dipeptidyl peptidase-4 inhibitors and the risk of bullous pemphigoid among patients with type 2 diabetes

Date of ISAC Approval: 
Lay Summary: 
Dipeptidyl peptidase-4 (DPP-4) inhibitors are drugs used to treat type 2 diabetes. Since their introduction in the United Kingdom in 2007, they have become increasingly popular. DPP-4 inhibitors lower blood sugar and do not cause weight gain or rapid drops in blood sugar levels like some other antidiabetic drugs. However, there are some reports suggesting that they may increase the risk of bullous pemphigoid, a rare but potentially life-threatening disease of the skin. To date, this possible association has not been well studied. Thus, we will investigate this possible link by using the Clinical Practice Research Datalink. This study will provide important information on the safety of DPP-4 inhibitors.
Technical Summary: 
Dipeptidyl peptidase-4 (DPP-4) inhibitors are typically used as second- to third-line treatments in the management of type 2 diabetes. While they effectively lower blood glucose via inhibition of the DPP-4 enzyme, there is some evidence that inhibiting this enzyme may generate autoimmune-related adverse events. Indeed, several case reports and few small case-control studies have suggested that use of DPP-4 inhibitors may be associated with an increased risk of bullous pemphigoid (BP), a rare blistering skin condition. However, these studies had methodological shortcomings that limit the validity of their findings. To address this question, we will assemble a cohort of approximately 170,000 patients newly-treated with antidiabetic drugs between January 2007 and March 2018. Time-dependent Cox proportional hazards models will be used to estimate hazard ratios with 95% confidence intervals of BP associated with use of DPP-4 inhibitors, compared with use of other second- to third-line antidiabetic drugs. Secondary analyses will assess whether risk varies by duration of use and by individual DPP-4 inhibitors.
Health Outcomes to be Measured: 
Incident diagnosis of BP.

Samy Suissa - Chief Investigator - McGill University
Antonios Douros - Collaborator - McGill University
Hui (Hoi) Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Julie Rouette - Collaborator - McGill University
Dr Kristian Filion - Collaborator - McGill University
Dr Laurent Azoulay - Collaborator - McGill University
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - McGill University