Fibates have withstood a large number of clinical applications around the world and have been proven to reduce triglycerides and increase high-density lipoprotein levels by activating peroxidase proliferator-activated receptors (PPAR). Fibrates, lipid-lowering drugs, not only regulate lipids but also have certain hypoglycemic effects.
Fibates have withstood a large number of clinical applications around the world and have been proven to reduce triglycerides and increase high-density lipoprotein levels by activating peroxidase proliferator-activated receptors (PPAR). Fibrates have certain lipid-lowering effects while regulating lipids. Among them, bezafibrate has the effects of regulating lipids, improving insulin resistance (IR), and reducing fasting blood sugar in non-obese T2DM patients, and its improvement The effect on glucose metabolism is superior to that of other fibrates.
Anti-atherosclerosis
The main effects of bezafibrate on blood lipid metabolism are to enhance lipoprotein lipase activity, promote the hydrolysis of triglyceride components in triglyceride-rich lipoprotein particles, and activate PPARα to promote triglyceride-rich lipoproteins. Effective clearance; bezafibrate can reduce the production of fatty acids through the human mitochondrial β-oxidation pathway; increase the activity of LDL receptors on the cell surface, increase the number of LDL lipoprotein receptors, and reduce LDL-C and cholesterol in plasma. Bezafibrate reduces lipoprotein and cholesterol arterial membrane damage through lipid-lowering effects; in addition, impaired vascular endothelial cell function is an important feature of atherosclerosis, and bezafibrate can significantly improve blood flow-mediated endothelial relaxation function. , can also inhibit the inflammatory response, reduce the level of acute phase proteins in plasma, and reduce the production of procoagulant factors, thus exerting an anti-atherosclerotic effect.
Delay the progression of diabetes
A large number of studies have shown that the incidence of diabetes in patients taking bezafibrate is significantly lower than that in patients taking other fibrates, and the degree of reduction is more prominent as the duration of treatment increases. In addition, bezafibrate can delay the progression of diabetes. Type 2 diabetes patients taking bezafibrate have a lower risk of developing the use of hypoglycemic drugs or developing insulin than type 2 diabetes patients taking other fibrate drugs. .
The pathogenesis of type 2 diabetes is insulin resistance and defective pancreatic islet secretion function. Apoptosis of pancreatic β-cells is an important cause of functional decline, and β-cell apoptosis is closely related to lipotoxicity. The possible mechanisms by which bezafibrate protects pancreatic β-cells include reducing fatty acid synthesis and damage to pancreatic β-cells; inhibiting the NF-KB pathway, reducing DNA damage and β-cell apoptosis; the Caspase pathway is a classic apoptosis pathway. Research has found that Bezafibrate can downregulate caspase-3 expression in pancreatic islets of type 2 diabetic rats.
The effect of bezafibrate on insulin resistance may be to reduce the inhibitory effect of high fatty acids on insulin, enhance insulin’s ability to process glucose; reduce plasma triglyceride levels, so that skeletal muscle is closely related to the occurrence of IR and obesity. The content of triglycerides in the patient’s body is reduced; bezafibrate can improve the patient’s vascular endothelial function by reducing blood lipid levels, so it is possible to further improve the patient’s IR on this basis.
Bezafibrate can activate all three PPAR isoforms, and the effects on glucose metabolism may also be through activation of PPARγ and PPARβ/δ. In the study by Shiochi H, the glucose infusion rate was increased from 5.78 to 6.78 mg/kg/min, and bezafibrate showed similar drug effects as pioglitazone and metformin in improving peripheral insulin resistance. Compared with PPARγ-specific agonists, there was no significant change in BMI of patients in the bezafibrate group before and after treatment. It can be speculated that bezafibrate, as a pan-PPAR agonist, can improve insulin sensitivity by activating PPARγ and at the same time activate PPARβ/δ to prevent Cause weight gain.
Optimize lipid lowering in combination with statins
Statins are currently the cornerstone of the treatment and prevention of atherosclerosis associated with cardiovascular disease. However, although an increasing number of studies confirm that statin therapy alone can lower LDL-C, dyslipidemia and insulin resistance remain significant cardiovascular risks in patients with atherosclerosis, and dyslipidemia and insulin resistance are type 2 Typical features of diabetes and metabolic syndrome. Bezafibrate, the main fibrate, reduces the risk associated with high triglycerides and low HDL. Studies have confirmed that combined treatment with statins and bezafibrate is more effective than statins alone in controlling blood lipids in patients with acute coronary syndrome. The increase in apoA5, which has a negative regulatory effect on plasma TG levels, may be the reason for these two The synergistic effect of two drugs on blood pressure control. Klempfner et al.’s study confirmed that the side effects of combined use of statins and fibrates are no greater than when used alone. Therefore, combined treatment with statins and fibrates can be recommended for patients with acute coronary syndrome.
Bezafibrate, as a pan-PPAR agonist, can improve atherosclerotic dyslipidemia and insulin resistance, reduce plasma triglyceride and blood glucose levels, increase HDL-C and reduce small and dense LDL particles. Bezafibrate can reduce the incidence of diabetes and delay the progression of existing diabetes, and its lipid-lowering combination with statins can more effectively control blood lipids and reduce cardiovascular risk.
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