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

Abstract

Aims: To evaluate the real-world effect of dipeptidyl peptidase-4 inhibitor (DPP4i) on the incidence of autoimmune diseases (AD), including rheumatoid arthritis (RA), inflammatory bowel diseases, multiple sclerosis and systemic lupus erythematosus. Methods: We identified new users of DPP4i (n = 497 619) or non-DPP4i (n = 643 165) oral combination therapy between 1 January 2011 and 30 June 2015 among patients with type 2 diabetes mellitus in the Korean national health insurance claims database. Patients were followed from the date of initiation of combination therapy until AD outcome, censoring for treatment discontinuation or switching, death or end of study (31 August 2016). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for RA, inflammatory bowel diseases, other AD (multiple sclerosis and systemic lupus erythematosus), and the composite of all outcomes were estimated using propensity score (PS)-adjusted Cox model. Results: In the PS-weighted and PS-matched analysis, the risk of incident RA was decreased for DPP4i initiators compared with non-DPP4i initiators (aHR 0.67 [95% CI 0.49-0.92] and aHR 0.72 [95% CI 0.51-1.01], respectively). In both analyses, the risk of incident composite AD was also decreased for DPP4i initiators compared with non-DPP4i initiators (aHR 0.82 [95% CI 0.68-0.99] and aHR 0.76 [95% CI 0.62-0.93], respectively). Conclusions:In this large population-based cohort study, upfront DPP4i combination therapy was associated with a lower risk of composite AD compared with initial non-DPP4i combination therapy.

Dipeptidyl peptidase-4 inhibitors and the risks of autoimmune diseases in type 2 diabetes mellitus patients in Taiwan: a nationwide population-based cohort study

“…In addition, another population-based study conducted by Kim et al found that DPP-4 inhibitors may reduce the risk of RA and composite autoimmune disease [36]. Another population-based cohort study using Korean National Health Insurance Claims Database found that the risk of incident RA and composite AD was decreased for DPP4i initiators compared with non-DPP4i initiators, which was consistent with our findings [37]. Our cohort study, which had a follow-up period of 5 years between January 2009 and December 2013, is distinct because we included large Asian population (387,099 in DPP-4i group vs. 387,099 in DPP-4i-naive group).…”

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

“…In a large cohort of diabetic patients, those initiating DPP4i combination therapy appeared to have a decreased risk of autoimmune diseases including RA (hazard ratio 0.66) compared with those initiating non-DPP4i combination therapy (Kim et al, 2015). Similar result was found in a large population-based cohort study conducted by Seong (Seong, Yee, & Gwak, 2019). However, using the United Kingdom CPRD, Douros conducted a cohort study among 144,603 patients with T2DM initiating OADs between 2007 and 2016, and found that use of DPP4is is not associated with any increased/decreased risk of incident RA .…”

“…Decreased risk in T2DM patients (Kim et al, 2015;Seong et al, 2019) No association in T2DM patients Increased disease severity in animal model (Busso et al, 2005;Ospelt et al, 2010) Allograft rejection…”

DPP4 inhibition: Preventing SARS‐CoV‐2 infection and/or progression of COVID‐19?

“…For example, pharmacological inhibition of DPP4 decreased incidence, onset of symptoms and overall disease severity in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis 23 . This is consistent with human data, where inhibitors of DPP4/CD26 suppress activation of Myelin basic protein (MBP)‐specific CD4+ T‐cell clones, 24 and with observations from population‐based cohort studies where DPP4i usage was associated with a 30% lower risk of incident autoimmune diseases 25,26 . Interestingly, in an experimental model of acute respiratory distress syndrome (ARDS), which represent the main death cause of SARS‐CoV‐2 infected patients, DPP4 inhibition by sitagliptin alleviated histological findings of lung injury by inhibiting proinflammatory cytokines IL‐1β, TNFα, and IL‐6 27 .…”