DPP-4 inhibitors may increase bullous pemphigoid risk in diabetes

Dipeptidyl peptidase-4 inhibition to treat type 2 diabetes was associated with an elevated risk for bullous pemphigoid, according to a study.

“Despite several recent reports on the elevated risk of bullous pemphigoid in patients with type 2 diabetes treated with dipeptidyl peptidase-4 (DPP-4) inhibitors, evidence on the absolute risk and comparative safety against other antidiabetics is limited,” Hemin Lee, MD, MPH, of the division of pharmacoepidemiology and pharmacoeconomics in the department of medicine at Brigham and Women’s Hospital, Boston, and colleagues wrote.

In the cohort study, Lee and colleagues assessed data from Optum Clinformatics Data Mart, IBM MarketScan Research Database and Medicare to compare incidence rates of bullous pemphigoid associated with DPP-4 inhibitors vs. those reported for second-generation sulfonylureas.

Eligible participants included those with type 2 diabetes who initiated treatment with one of the two drug types. Patients included in the Optum cohort were identified from Oct. 17, 2006, to Dec. 31, 2018, while the IBM group included patients identified from Oct. 17, 2006, to Dec. 31, 2017. Medicare patients were identified from Jan. 1, 2006, to Dec. 31, 2016.

Bullous pemphigoid, as assessed by diagnostic codes, served as the primary outcome for the 1,664,880 patients who initiated treatment during the study. The researchers also included subgroup analyses based on age, sex, race and individual DPP-4 agents.

Both treatment arms were almost evenly split between men and women. The mean age of patients in both groups was 63.9 years.

Results showed that DPP-4 inhibitors yielded 0.42 cases of bullous pemphigoid per 1,000 person-years compared with 0.31 cases per 1,000 person-years for sulfonylureas (HR = 1.42; 95% CI, 1.17-1.72).

The difference was more pronounced for individuals older than 65 years, according to the findings. In this age group, bullous pemphigoid occurred at a rate of 0.79 per 1,000 person-years in the DPP-4 group and 0.49 per 1,000 person-years in the sulfonylurea group (HR = 1.62; 95% CI, 1.32-1.99).

White individuals in the DPP-4 group also had an elevated risk for the primary endpoint compared with patients of other races (0.93 vs. 0.54 per 1,000 person-years; HR = 1.70; 95% CI, 1.30-2.24), as did those who were treated with linagliptin (1.20 vs. 0.55 per 1,000 person-years; HR = 1.68; 95% CI, 1.16-2.43).

“This study found that patients who initiated DPP-4 inhibitor therapy had higher risk of bullous pemphigoid than those who initiated second-generation sulfonylurea therapy,” the researchers wrote. “Clinicians should be aware of this rare adverse effect of DPP-4 inhibitors in subgroups of patients who are older, white and linagliptin users.”