This is a prospective, randomized, controlled, parallel-group, open-label clinical trial that will be conducted at the Rheumatology Outpatient Clinic of Al-Zahraa University Hospital, Cairo. The study will include adult patients aged 18 to 65 years with rheumatoid arthritis diagnosed according to the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria, who have been receiving stable methotrexate treatment for at least 12 weeks and have active rheumatoid arthritis despite methotrexate therapy. A total of 90 participants will be enrolled and randomly allocated in a 1:1:1 ratio into three groups, with 30 participants in each group. Group I will receive dapagliflozin 10 mg once daily in addition to standard methotrexate therapy for 3 months. Group II will receive empagliflozin 10 mg once daily in addition to standard methotrexate therapy for 3 months. Group III will receive standard methotrexate therapy alone for 3 months. Clinical and laboratory assessments will be performed at baseline and after 3 months. Disease activity will be assessed using the Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP). Laboratory assessments will include serum matrix metalloproteinase-3 (MMP-3), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complete blood count, alanine aminotransferase, aspartate aminotransferase, serum creatinine, and estimated glomerular filtration rate. Safety and tolerability will also be assessed throughout the study. The primary outcome is the change in DAS28-CRP from baseline to 3 months. Secondary outcomes include the change in serum MMP-3 concentration from baseline to 3 months, assessment of adverse drug reactions, and treatment discontinuation due to adverse drug reactions.
