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

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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.

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    Authors and Affiliations

    1. Section of Pharmacology, Department of Experimental Medicine, Pharmacoepidemiology and Pharmacovigilance Centre of the Campania Region, Second University of Naples, via L. de Crecchio 7, 80138, Naples, Italy

      Annamaria Mascolo, Concetta Rafaniello, Liberata Sportiello, Maurizio Sessa, Daniela Cimmaruta, Francesco Rossi & Annalisa Capuano

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    1. Annamaria Mascolo
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    2. Concetta Rafaniello
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    Correspondence to Annamaria Mascolo.

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    Annamaria Mascolo, Concetta Rafaniello, Liberata Sportiello, Maurizio Sessa, Daniela Cimmaruta, Francesco Rossi and Annalisa Capuano declare no conflicts of interest.

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    A. Mascolo and C. Rafaniello equally contributed to the manuscript.

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    Mascolo, A., Rafaniello, C., Sportiello, L. et al. Dipeptidyl Peptidase (DPP)-4 Inhibitor-Induced Arthritis/Arthralgia: A Review of Clinical Cases. Drug Saf 39, 401–407 (2016). https://doi.org/10.1007/s40264-016-0399-8

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