Livedoid and Purpuric Skin Eruptions Associated With Coagulopathy in Severe COVID-19.

Abstract

Despite several recent reports on the elevated risk of bullous pemphigoid in patients with type 2 diabetes treated with dipeptidyl peptidase (DPP)-4 inhibitors, evidence on the absolute risk and comparative safety against other antidiabetic agents is limited. To characterize the incidence rate of bullous pemphigoid associated with DPP-4 inhibitor use in comparison to 2^nd generation sulfonylureas. In this multi-database cohort study using 2 large commercial insurance claims data (Optum Clinformatics Data Mart and IBM MarketScan Research Database) and Medicare data from 2006 to 2018, we included type 2 diabetes patients initiating DPP-4 inhibitors or 2^nd generation sulfonylurea. The primary outcome of the study was bullous pemphigoid, identified using diagnosis codes. After 1:1 propensity score matching, we estimated the incidence rates of bullous pemphigoid and the hazard ratios (HR) with 95% confidence intervals (CI) comparing DPP-4 inhibitor initiators and 2^nd generation sulfonylurea initiators. Subgroup analyses by age, gender, race, and individual DPP-4 agents were performed. The results from each database were pooled using inverse-variance fixed-effects meta-analysis. A total of 1,664,880 initiators of DPP-4 inhibitors and sulfonylurea were included. The incidence rate of bullous pemphigoid per 1,000-person years was 0.42 in the DPP-4 inhibitors versus 0.31 in the sulfonylurea inhibitors. ( HR, 1.42; 95% CI, 1.17–1.72). Higher rates per 1,000 person years for DPP-4 inhibitors versus sulfonylurea were seen in those aged ≥65 years (0.79 versus 0.49, HR, 1.62; 95% CI, 1.32–1.99), of white race (0.93 versus 0.54, HR, 1.70; 95% CI, 1.30–2.24), and treated with linagliptin (1.20 versus 0.55, HR, 1.68; 95% CI, 1.16–2.43). DPP-4 inhibitor initiators have higher risk of bullous pemphigoid than 2^nd generation sulfonylurea. Clinicians should be aware of this rare side effect of DPP-4 inhibitors in subgroups of older age, white race, and linagliptin users.