A Research on Cardiovascular safety and benefits of type 2 diabetes drugs

Type 2 diabetes is a chronic non-infectious disease related to glucose metabolism disorder, and its prevalence is increasing year by year. Cardiovascular disease is the leading cause of death in type 2 diabetes, among which atherosclerotic cardiovascular disease is the most common cardiovascular disease and the main cause of death in type 2 diabetes. Reducing cardiovascular events is an important goal of diabetes prevention and treatment. The cardiovascular safety of hypoglycemic drugs has received extensive attention from the medical community since the "rosiglitazone incident". Traditional type 2 diabetes drugs lack strong clinical research evidence of cardiovascular benefits, and some newly marketed type 2 diabetes drugs have clear cardiovascular benefits and have obvious advantages in cardiovascular protection. Diabetic patients with cardiovascular disease or high risk should be differentiated and type 2 diabetes drugs with clear evidence of cardiovascular benefit should be selected. Therefore, this article sorts out and reviews the existing domestic and foreign evidence of cardiovascular safety and benefits of hypoglycemic drugs.

Cardiovascular safety of novel hypoglycemic agents

New type 2 diabetes drugs are divided into two categories, namely SGLT2i drugs (empagliflozin, canagliflozin) and GLP-1RA drugs (liraglutide, semaglutide, albiglutide, dulaglutide). Studies have shown that both classes of drugs have good cardiovascular safety and clear evidence of cardiovascular benefit.

Mechanisms and differences of cardiovascular benefits of new hypoglycemic drugs

Mechanisms

There are differences between GLP-1RA and SGLT2i in terms of cardiovascular protection mechanisms. GLP-1RA can improve multiple cardiovascular risk factors (regulate blood lipids, reduce blood sugar, blood pressure, reduce body weight, improve insulin resistance), directly promote the recovery of cardiovascular endothelial cell function and myocardial function after non-fatal myocardial infarction, and enhance ischemia Cardiac function and left ventricular ejection fraction, etc. The cardiovascular protective effect of GLP-1RA is mainly to improve the process of atherosclerosis and reduce the risk of stroke and myocardial infarction. SGLT2i can reduce glucotoxicity, reduce inflammation and oxidative stress, improve cardiac afterload, improve myocardial metabolites, improve myocardial metabolic efficiency, improve myocardial remodeling and fibrosis, and ultimately improve cardiac function through diuresis, sodium excretion, and glucose excretion. It can improve renal function by restoring the balance of bulb and tube, and break the vicious circle of cardio-renal pathophysiology; it can also reduce blood pressure and body weight and improve multiple cardiovascular risk factors. The cardiovascular protective effect of SGLT2i is mainly to improve volume overload, correct hemodynamic disturbance, and reduce the risk of heart failure.

Differences

There were differences in the incidence of cardiovascular endpoints among different types of GLP-1RA. Although similar drugs have similar mechanisms of action, different molecular structures and pharmacokinetics may lead to differences in clinical effects.

There are also differences in the cardiovascular benefits of SGLT2i drugs. Empagliflozin can reduce the risk of major adverse cardiovascular events（MACE）and the risk of cardiovascular death; canagliflozin can reduce the risk of MACE without reducing the risk of cardiovascular death; dapagliflozin Neither nor ipagliflozin reduced MACE nor the risk of cardiovascular death. But these drugs can reduce the risk of heart failure hospitalization. Whether outcome differences in cardiovascular benefit with SGLT2i drugs are related to study population heterogeneity is currently inconclusive. There is also a lack of randomized controlled trials that directly compare different drugs, so the differences in the risk of MACE and the risk of cardiovascular death need to be further studied.

Conclusion

These studies providing strong evidence of cardiovascular benefits provide a solution for the treatment of type 2 diabetes mellitus beyond glycemic control to better manage serious cardiovascular complications, especially in patients with cardiovascular disease or high-risk factors. With more and more important role, the pattern of treatment of type 2 diabetes drugs is bound to undergo major changes. At present, many national guidelines recommend the use of GLP-1RA in type 2 diabetes mellitus patients with middle atherosclerotic cardiovascular disease, and SGLT2i is recommended for type 2 diabetes mellitus patients with heart failure. It is expected that there will be more clinical research evidence to confirm that the cardiovascular outcomes of type 2 diabetes mellitus patients can be improved and benefited by hypoglycemic drug treatment, and there will be broader clinical application practice to change the current difficult situation of "three lows and one high" (low awareness rate, low treatment rate, low compliance rate and high prevalence rate) in the diagnosis and treatment of type 2 diabetes.