DPP-4 Inhibitors May Up Risk of Bullous Pemphigoid in Some Diabetics

By David Douglas

July 31, 2020

NEW YORK (Reuters Health) - In certain patients with type 2 diabetes, starting dipeptidyl peptidase 4 (DPP-4) inhibitors may increase the risk of developing bullous pemphigoid, compared with therapy with second-generation sulfonylurea, according to new research.

However, as Dr. Hermin Lee of Brigham and Women's Hospital, in Boston, told Reuters Health by email, "the absolute risk of the event was low, and clinically, we see DPP-4 inhibitor-induced bullous pemphigoid cases remitting after discontinuing the culprit drug."

In a paper in JAMA Dermatology, Dr. Lee and colleagues note that there have been several reports of this risk. But "these studies do not provide absolute risk of bullous pemphigoid and can be subject to several methodological limitations."

To investigate further, the researchers examined insurance and Medicare data covering 2006 to 2017 and identified more than 1.6 million patients who started therapy with DPP-4 inhibitors or second-generation sulfonylurea during that period. Their mean age was 63.9 years.

"We chose sulfonylureas as the active comparator," say the researchers, "because they remain the most commonly used second-line agents in diabetes treatment and are not known to cause bullous pemphigoid."

The team found that the incidence rate of bullous pemphigoid per 1,000 person-years was 0.42 in the DPP-4 inhibitor group, significantly higher than the 0.31 in the sulfonylurea group (hazard ratio, 1.42).

In those over 65, the risk was greater (HR, 1.62), as was also true of being white (HR, 1.70) or treated with linagliptin (HR, 1.68). Linagliptin, the researchers point out, "was the only agent with a statistically significant association."

They note that, "Despite all the signals, the mechanism behind an increased risk of bullous pemphigoid with DPP-4 inhibitors remains to be elucidated."

"Nevertheless," Dr. Lee concluded, "clinicians should increase their awareness on the potential onset of bullous disease in patients initiating DPP-4 inhibitors especially those with older age, white race, and initiating linagliptin."

A spokesperson for Boehringer Ingelheim, which markets linagliptin as Tradjenta, told Reuters Health by email, "Patient safety is our utmost priority, and we actively monitor the safety of our products on an ongoing basis through clinical trials, observational studies and spontaneous reporting in everyday use. Bullous pemphigoid is a known adverse reaction associated with DPP-4 inhibitors and is included in the Warnings and Precautions section of the prescribing information for Tradjenta. If bullous pemphigoid is suspected, healthcare providers are advised to discontinue Tradjenta and consider referral to a dermatologist for diagnosis and appropriate treatment."

"The safety profile of Tradjenta was established through a robust clinical trial program, including the CARMELINA cardiovascular outcome and renal safety trial. In the CARMELINA trial, bullous pemphigoid occurred in 7 people (0.2%) in the Tradjenta treatment group, compared to none in the placebo group. We are confident in the benefit-risk profile of Tradjenta as outlined in the prescribing information."

The study did not have commercial funding.

SOURCE: https://bit.ly/39C7aE5 JAMA Dermatology, online July 22, 2020.