Background: A worldwide health epidemic, type 2 diabetes mellitus was significantly influenced by chronic inflammation, which led to increased insulin resistance (IR). The most widely practiced form of therapy used to control musculoskeletal pain in people with diabetes is non-steroidal anti-inflammatory drugs (NSAIDs), which provide their action by inhibiting cyclooxygenase enzyme (COX). COX1, COX2, and COX3 are distinct isoforms of the cyclooxygenase enzyme. The potential anti-inflammatory benefits of cyclooxygenase-2 (COX-2) inhibitors, both selective and non-selective, have been investigated concerning the management of type 2 diabetes patients. Objective: the purpose of this research is to explore the impact of highly selective celecoxib and relatively selective diclofenac (COX-2) inhibitors on insulin sensitivity in type 2 diabetes patients. Methods: A sample of 136 patients with T2DM (92 females, 44 males) and 64 healthy controls (36 females, 28 males) was formed. Two groups of patients, Group 1 (hyperlipidemia) and Group 2 (normolipidemic), were created. Each group received treatment with either diclofenac or celecoxib in half. Insulin sensitivity was ascertained using the quantitative insulin sensitivity check index (QUICKI) formula. Results: Both normolipidemic and hyperlipidemic diabetics had higher fasting plasma glucose levels (p-value) and lower QUICKI scores compared to the controls. Diclofenac significantly increased serum insulin and decreased fasting glucose in hyperlipidemic diabetics, while celecoxib also reduced fasting glucose and QUICKI scores in hyperlipidemic. In normolipidemic diabetics, diclofenac decreased fasting glucose and increased insulin, whereas celecoxib increased insulin but decreased QUICKI scores. Conclusion: Targeted COX-2 inhibitors such as celecoxib may considerably provide valuable benefits, including enhanced insulin sensitivity, metabolic function, and overall health.
