Prevalence of chronic disorders like arthritis is frequently observed in diabetic patients, especially among the geriatric population. To combat such a situation, non-steroidal anti-inflammatory drugs (NSAIDs) are mostly co-prescribed along with antidiabetics. Thus present study tried to evaluate the safety and efficacy of concomitant use of drugs in animals induced with comorbid conditions. Diabetes and chronic inflammation were induced in rats by Streptozotocin and Nicotinamide and Freund’s Complete Adjuvant respectively. These medical conditions were treated with antidiabetic Metformin and NSAID Diclofenac Sodium for 28 days. Blood glucose, paw edema were recorded weekly. At the end of the study duration, Insulin, C-peptide, cytokines in serum, oxidative stress biomarkers in liver and kidney tissues were estimated. Concomitant therapy of Metformin and Diclofenac Sodium was successful in reducing the glucose level and inflammation parameters. However, reduction by 30.06% and 46.51% in insulin and C-peptide levels respectively were evident in the rats treated with concomitant medications as compared to the normal. Concomitant therapy also failed to restore the normal levels of the pro-inflammatory cytokines. Perturbation was also evident in the antioxidant status of the tissues. Results from this study can thus be utilized to optimize the therapeutic regimen of patients to ensure safe medication.