Arthritis & Rheumatology最新文献

Objective: GLP-1 receptor agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2is) facilitate weight loss and exhibit immunomodulatory effects, but their impact on the risk of developing autoimmune rheumatic diseases (ARDs) is unclear. We compared ARD incidence following initiation of GLP-1RAs, or SGLT2is, vs. a weight-neutral comparator (DPP4 inhibitors, DPP4is).

Methods: We performed a population-based cohort study using administrative health data from a Canadian province with universal healthcare. We included adults with type 2 diabetes (T2D) and no prior ARD initiating a GLP-1RA, SGLT2i, or DPP4i between 2014/01/01 and 2022/12/31. Incident ARD cases, including rheumatoid arthritis, psoriatic disease, axial spondyloarthritis, and systemic ARDs (SARDs; systemic lupus erythematosus, systemic sclerosis, Sjögren's disease, idiopathic inflammatory myopathies, and systemic vasculitides), were identified using validated algorithms. Propensity score (PS) weighting was used to balance cohorts at treatment initiation, then hazard ratios (HRs) were estimated using Cox regression.

Results: Among 229,300 adults, 49,514 initiated GLP-1RAs, 101,925 initiated SGLT2is, and 77,861 initiated DPP4is. After PS weighting, ARD incidence per 10,000 person-years was 29.1 (95% CI, 23.5-35.5) with GLP-1RAs, 24.4 (19.8-29.7) with SGLT2is, and 27.3 (22.1-33.4) with DPP4is. Mean follow-up was 1.3-1.6 years. Relative to DPP4is, adjusted HRs of ARD were 1.04 (0.81-1.33) with GLP-1RAs and 0.93 (0.75-1.16) with SGLT2is. Risk of SARDs, but not other diseases, was lower with SGLT2is vs. DPP4is (aHR, 0.51 [0.31-0.84]).

Conclusion: Neither GLP-1RA nor SGLT2i treatment was associated with lower ARD risk vs. DPP4is in adults with T2D; however, SGLT2i use was associated with significantly lower risk of SARDs, warranting further study.

Introduction: Rheumatoid sarcopenia, characterized by the progressive loss of skeletal muscle mass and function, is a frequent comorbidity in rheumatoid arthritis (RA), linked to prolonged, severe systemic inflammation. Purinergic signaling (adenosine, AMP, and ATP) plays a crucial role in inflammation, myogenesis, and muscle hypertrophy. Dipyridamole, an antiplatelet agent, enhances extracellular adenosine availability, alters AMP/ATP ratio and activates A2BR and AMPK pathways. We aim to investigate its potential use as a therapeutic agent for RA and rheumatoid sarcopenia.

Methods: K/BxN-induced mice received preventive or therapeutic dipyridamole treatment daily and were sacrificed at joint inflammation peak and resolution stage. Motor activity tests and dual-energy x-ray absorptiometry (DXA) were performed. C-reactive protein (CRP) levels were also analyzed in serum and cytokines array was performed in serum and muscle. Histology of tibialis anterior (TA) and talus joint were studied. Myogenesis, purinergic system, atrophy and senescence key markers were analyzed via Western Blot and RT-PCR in gastrocnemius (GA). Nucleotide content via HPLC was performed. 2D and 3D models with C2C12 cells were done.

Results: Dipyridamole reduced joint, muscle, and systemic inflammation, counteracting muscle wasting and physical inactivity via an anabolic mechanism involving down-regulation of myostatin expression. This effect was mediated by increased adenosine and AMP levels, which activate adenosine A2B receptor and downstream cyclic AMP/AMPK signaling pathways.

Conclusion: These results support a dual role for dipyridamole in RA, combining robust anti-inflammatory effects with a novel, myostatin-linked anabolic action on sarcopenia, mediated through adenosine and AMPK signaling, distinct from conventional therapeutic mechanisms.