Assessing the effects of GLP1 RA Vs SGLT2 Inhibitors vs. Standard of care in joint pain, physical function, stiffness, and improving Quality of Life for patients with type 2 diabetes.

Osteoarthritis (OA) is a multifactorial joint disease related to multiple inflammatory pathways which are triggered by mechanical and cellular stress, leading to increased production of pro-inflammatory mediators, reactive oxygen species, advanced glycation end products (AGEs). These mediators promote the release of proteolytic enzymes, which degrade the cartilage matrix. A recent study emphasized on the relation between metabolic syndrome and OA, considering metabolic dysregulation as a major factor in OA progression.

GLP-1 receptor agonists lower blood sugar by boosting glucose-dependent insulin release, reducing glucagon secretion, and slowing stomach emptying. GLP-1RA is present in both healthy and osteoarthritic cartilage, indicating a direct effect on chondrocytes. so it can decrease the accumulation of AGEs, which is the main cause of OA. It also reduces appetite, leading to weight loss which decreases the mechanical stress on joints. GLP downregulates proinflammatory cytokines (IL-6, TNF-a). also inhibits NF-κB pathway. which has a role in promoting osteoclast formation, so GLP plays a protective role in OA.

Inclusion Criteria:

• Adults aged above 50 years old with a previous diagnosis of T2DM according to ADA 2025, who have been on either SGLT2 inhibitors or GLP-1 analogs for at least one year.

Exclusion Criteria:

• individuals with Type 1 Diabetes Mellitus
• non-diabetic individuals
• those taking prandial insulin
• patients with arthritis without osteoarthritis,
• those taking other medications contraindicated with study medications,
• pregnant or breastfeeding females
• those allergic to active ingredients,
• those using corticosteroids, Autoimmune disease patients or patients receiving immunotherapies, monoclonal antibody targeting TNF-α or IL-6.

130 T2DM patients will be admitted in each group Group 1 : T2DM patients receiving SGLT2 inhibitors for at least 1 year added to their standard of care Group 2: T2DM patients receiving GLP1 analogues for at least 1 year added to their standard of care Group 3: T2DM patients receiving only standard of care