Dipeptidyl Peptidase (DPP)-4 Inhibitor-Induced Arthritis/Arthralgia: A Review of Clinical Cases

Abstract

Dipeptidyl peptidase (DPP)-4 inhibitors are a class of oral drugs used for the treatment of type 2 diabetes mellitus (T2DM). The pharmacological inhibition of DPP-4 seems to also induce adverse events related to cytokine-induced inflammation. Recently, several clinical cases regarding the association of DPP-4 inhibitors and the onset of arthritis/arthralgia have been reported in the literature. Various mechanisms could be responsible for DPP-4 inhibitor-induced arthritis/arthralgia, and the increase of cytokines, chemokines, matrix metalloproteinases (MMPs) and genetic factors plays an important role. The US FDA published a safety announcement regarding the entire drug class, encouraging healthcare professionals and patients to pay attention to the occurrence of arthralgia during treatment with DPP-4 inhibitors; arthralgia could be assessed as a class adverse drug event for DPP-4 inhibitors. To summarize the evidence on the correlation between DPP-4 inhibitors and arthritis/arthralgia, and to explain the measures taken by the FDA with regard to arthralgia risk, we performed a literature review of recent evidence concerning this association. This review shows the necessity of other studies to better define the association between DPP-4 inhibitors and arthritis/arthralgia.

Adverse drug reactions during hepatitis C treatment with direct-acting antivirals: The role of medication errors, their impact on treatment discontinuation and their preventability. New insights from the Campania Region (Italy) spontaneous reporting syste

“…This study is part of a set of initiatives to promote drug safety developed by the Campania Pharmacovigilance Regional Centre during the last decade. 11,[25][26][27][28][29] By re-evaluating the ICSRs, we found that <2% of cases were deemed preventable. The most commonly detected preventable criterion was labelled drug-drug interaction of coadministered drugs with DAA.…”

“…This study is part of a set of initiatives to promote drug safety developed by the Campania Pharmacovigilance Regional Centre during the last decade . By re‐evaluating the ICSRs, we found that <2% of cases were deemed preventable.…”

Dipeptidyl peptidase‐4 inhibitors lower the risk of autoimmune disease in patients with type 2 diabetes mellitus: A nationwide population‐based cohort study

“…Currently, however, clinical evidence showing the epidemiological effect of DPP‐4 inhibitors on autoimmune diseases is scarce. In addition, several studies rather raised concerns about severe joint pain related to the use of DPP‐4 inhibitors …”

DPP-4 inhibitor (sitagliptin)-induced seronegative rheumatoid arthritis

“…Inhibitors of DPP-4 have been associated with many processes that could lead to the development of arthritis 4 18–27. Some of these processes perform a pathologic function only in the setting of a genetic predisposition 17 24 28.…”