## 4 Discussion
Similarly to the findings of this study, [PERSON] and [PERSON] demonstrated that combined metformin/gliclazide treatment significantly improved lipid profile, as evidenced by decreased total cholesterol and significantly increased HDL levels compared to the control group, when compared the study participants were compared [55]. The similar effects of monotherapy versus combination therapy on lipid profile, as demonstrated in this study, are consistent with a previous study that found similar efficacy of both drugs on lipid profile in the same patient [56]. Like most sulfonylurea, metformin has been shown to decrease oxidative stress [15; 23] effectively. Studies that have investigated the effect of glipizide on oxidative stress are scarce [57]. The studies showed reduced oxidant stress in diabetic rats, as in the present study, while the influence of metformin on oxidative stress was even more pronounced. Furthermore, the TAC of diabetic rats treated with metformin was significantly higher than that of rats treated with glipizide, highlighting the increased capacity of metformin to minimize oxidative stress compared to glipizide. Further, recent studies confirmed the valuable role of metformin in controlling oxidative stress [23; 58]. Moreover, the effect of metformin on oxidative stress was investigated in a study by [PERSON] et al. [58], demonstrating that metformin is more effective than lifestyle change alone in reducing oxidative stress in patients with type II DM. Similarly, a study by [PERSON] et al. [23] with a larger sample size of diabetic patients randomly assigned to metformin or a placebo, showed that treatment with metformin restored antioxidant status in patients with type II diabetes and suggested a cardioprotective role for metformin. This conclusion was later supported by SPREAD-DIMCAD investigators, who reported that treatment with metformin for three years substantially reduced major cardiovascular events compared to therapy with glipizide over a median follow-up time of 5 years [17]. Figure 8: The synergistic interactions between metformin and Glipizide in diabetes with different targets and mechanisms of action lead to decreased oxidative stress damages and prevented vascular complications of hyperglycemia. Our findings suggest that glipizide is more effective at treating dyslipidemia than metformin, which appears to contradict earlier clinical studies. A very preliminary investigation conducted by [PERSON] et al. [59] attempted to confirm the potential benefits of metformin over glipizide, as previously established in the SPREAD-DIMCAD study. In a 3-year study, [PERSON] and his group evaluated lipid profiles in serum samples obtained from diabetic patients treated with either metformin or glipizide. They confirmed that metformin was non-inferior to glipizide in lowering atherogenic lipids. In contrast, the present study showed that glipizide exerted a more powerful effect than metformin against atherogenic dyslipidemia, with markedly lower LDL levels in diabetic rats treated with glipizide compared to those treated with metformin. Likewise, we only observed a significant increase in HDL following treatment with glipizide, and not after treatment with metformin. Similarly, other studies have demonstrated similar patterns of changes in serum lipid profiles due to glipizide treatment [60, 61]. These results explain the mechanism of type 2 diabetes dyslipidemia, which was defined based on insulin resistance that distorts lipoprotein lipase to hepatic lipase ratio, resulting in decreased levels of HDL-cholesterol. The decline of HDL cholesterol esters is mainly due to increased cholesterol ester transfer protein (CETP) activity that eventually results in lower HDL cholesterol [10]. The mechanism for increasing triglyceride levels in hyperglyic individuals also includes decreasing lipoprotein lipase activity (LPL). LPL activity has been lower in Type II DM patients [62]. However, apart from the study by [PERSON] et al.