ABSTRACT
AIMS: This study aimed at investigating the efficacy of metformin as adjuvant therapy for obese knee osteoarthritis (OA) patients, considering its anti-inflammatory and cartilage-protective effects. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled study, 50 obese knee OA patients were assigned randomly to two groups, the metformin group (n = 25) which was treated with metformin 500 mg orally BID plus celecoxib 200 mg orally once daily, and the placebo group (n = 25) which was treated with placebo tablets BID plus celecoxib 200 mg orally once daily for 12 weeks. Cartilage Oligomeric Matrix Protein (COMP), C-terminal cross-linked telopeptide of type I collagen (CTX-1), and Interleukin 1-beta (IL-1ß) serum levels were measured, while Western Ontario and McMaster Universities Arthritis Index (WOMAC) score assessed knee pain, stiffness, and physical function at baseline and after 12 weeks. RESULTS: Following a 12-week treatment, the metformin group exhibited significantly reduced levels of COMP, CTX-1, and IL-1ß in the serum compared to the placebo group (p = 0.0081, p = 0.0106, and p = 0.0223, respectively). Furthermore, metformin group produced significant improvements in WOMAC total scale (p < 0.0001), specifically in knee pain, stiffness, and physical function compared to placebo group (p < 0.0001, p < 0.0001, and p < 0.0001, respectively). CONCLUSION: Metformin as an adjuvant therapy in obese knee OA patients may have beneficial effects on cartilage degradation and inflammation, as evidenced by the significant decreases in serum COMP, CTX-1, and IL-1ß levels. Additionally, metformin may improve clinical outcomes, as shown by the significant improvements in WOMAC scores. GOV ID: NCT05638893/Registered December 6, 2022 - Retrospectively.
Subject(s)
Metformin , Obesity , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/drug therapy , Double-Blind Method , Metformin/administration & dosage , Metformin/pharmacology , Male , Middle Aged , Female , Obesity/drug therapy , Aged , Celecoxib/administration & dosage , Celecoxib/pharmacology , Interleukin-1beta/blood , Cartilage Oligomeric Matrix Protein/blood , Treatment Outcome , Drug Therapy, Combination , Collagen Type I/bloodABSTRACT
BACKGROUND: Systemic lupus erythematosus is a chronic multisystemic autoimmune disease characterized by chronic inflammatory processes and failure of immune-regulatory mechanisms. Systemic lupus erythematosus is associated with increased risk for cardiovascular disease. In view of immunometabolic derangements of systemic lupus erythematosus, we investigated the roles of sucrose non-fermenting AMPK related kinase, Pentraxin 3, and DNA damage in the pathogenesis of systemic lupus erythematosus complicated with cardiovascular disease. METHODS: Forty systemic lupus erythematosus women with cardiovascular disease (systemic lupus erythematosus cases), 40 systemic lupus erythematosus women without cardiovascular disease, and 40 healthy controls were enrolled in this study. Demographic and clinical data were recorded. Plasma concentrations of sucrose non-fermenting AMPK related kinase and Pentraxin 3 were immunoassayed. Carotid intima media thickness, atherogenic, and DNA damage indices were also assessed. RESULTS: Plasma sucrose non-fermenting AMPK related kinase and Pentraxin 3 concentrations were increased in systemic lupus erythematosus cases with cardiovascular disease compared to systemic lupus erythematosus controls and healthy controls (P < 0.0001). In systemic lupus erythematosus cases, there was a positive correlation between sucrose non-fermenting AMPK related kinase and Pentraxin 3 (r = 0.57, P < 0.002). CONCLUSIONS: These data highlight a novel role of sucrose non-fermenting AMPK related kinase/Pentraxin 3 axis in systemic lupus erythematosus pathogenesis. Sucrose non-fermenting AMPK related kinase/Pentraxin 3 combined role in immunometabolic signaling and DNA damage response is proposed to accelerate cardiovascular complications in systemic lupus erythematosus patients.