Lixisenatide Tablet

1. Research Design

ELIXA study is a global, randomized, double-blind, placebo-controlled trial led by Professor Marc Pfeffer of Harvard University Medical School and Brigham Women's Hospital. A total of 6068 patients with type 2 glycuresis and acute coronary syndrome (ACS) were included in 49 countries. The average age of these patients is 60 years old, 30% are female, 76% are Caucasian, the average BMI is 30kg/m ², the average fasting blood glucose is 149mg/dL, the average HbA1c level is 7.7%, and the average course of illness is 9 years.Before merging with acute coronary syndrome, 22% of patients had a history of myocardial infarction (MI) and 22% had a history of heart failure. The average time interval from the onset of acute coronary syndrome to random allocation to the group is 72 days. 3034 patients received treatment with lixisenatide tablet (initial dose of 10 μ g/day, which can be increased to 20 μ g/day), while the remaining 3034 patients received placebo treatment.

The follow-up period exceeds 2 years, and some patients are followed up for up to 3 years.

The main composite study endpoint is cardiovascular death, myocardial infarction, stroke, or unstable angina requiring hospitalization.

2. Core Results: Neutral but Safe
After 3 years of follow-up, the cardiovascular outcomes of the Lixilalai group and the placebo group showed a high degree of consistency:

The conclusion is clear and definite: treatment with Liraglutidum does not increase the risk of cardiovascular adverse events. Professor Marc Pfeffer of Harvard Medical School clearly pointed out at the 2015 ADA annual meeting: "Among these type 2 glycuresis patients with high cardiovascular risk, the treatment of risilade is safe in cardiovascular aspects and can also bring metabolic benefits. This suggests that clinicians can be assured to use such GLP-1 receptor agonists as risilade to better control blood sugar. "

Dr. Matthew Riddle from Oregon Health and Science University further added, "Although the magnitude of weight loss and blood pressure reduction is not significant, the number of participants in this study is large, and these data have statistical significance, and may even have some clinical significance

There are differences in the cardiovascular performance of different GLP-1 receptor agonists, and understanding these differences can help with precise drug selection in clinical practice.

Professor Guo Yifang analyzed that Liraglutidum has a better effect on reducing HbA1c than Liraglutidum. The former has a better effect on reducing fasting blood glucose than Liraglutidum, but the latter has a better effect on reducing postprandial blood glucose than Liraglutidum. The weight reducing effect of Liraglutidum is also superior to that of Liraglutidum (Kapitza study). The GetGoal-X study compared the antihypertensive effects of exenatide and liraglutidum, and the results showed that exenatide reduced blood pressure by 2.9/1.3mmHg, while liraglutidum reduced blood pressure by 2.5/1.8mmHg, both of which were comparable.

The meta-analysis published in AME Clinical Research Reviews in 2023 further confirms that the meta-analysis of all CVOTs using GLP-1 receptor agonists found a 10% decrease in overall MACE risk (HR=0.90, 95% CI: 0.82~0.99; P=0.033), a 13% decrease in cardiovascular mortality risk (HR=0.87, 95% CI: 0.79~0.96; P=0.007), and a 12% decrease in all-cause mortality risk (HR=0.88, 95% CI: 0.81~0.95; P=0.002). This indicates that GLP-1 receptor agonists, as a whole, do have protective effects on the cardiovascular system, and the "neutral" results of liraglutidum may be related to its study design (striving to maintain similar blood glucose levels between the two groups) and drug properties (short acting, postprandial priority).

First, safe hypoglycemic choice for type 2 glycuresis sicks with acute coronary syndrome (ACS). The ELIXA study specifically included this highest risk population, demonstrating that liraglutidum does not increase the risk of cardiovascular events in this population and is a reliable choice for blood glucose management after ACS.

Secondly, the cardiovascular "hedging" strategy when combined with basal insulin. The combination of liraglutidum and basal insulin can double the HbA1c compliance rate (28% vs. 12%), while significantly reducing body weight and insulin dosage. The incidence of symptomatic hypoglycemia in participants with a history of basal insulin therapy was approximately half of that in the placebo group treated with levocetirizine.The weight loss effect of Lysimal precisely counteracts the weight gain effect of insulin, forming a cardiovascular risk management effect of "1+1<2".

Thirdly, the optimal plan for elderly cardiovascular high-risk sicks. The GetGoal-O study showed that in non fragile T2DM sicks aged 70 years or older, liraglutidum is effective and safe for weight loss, with symptomatic hypoglycemia only 5.7% (placebo group 12.7%). 28% of participants in the ELIXA study had moderate renal impairment, and there was no increased risk of cardiovascular adverse events in this subgroup with Risilar.

Fourthly, maintaining a hypoglycemic anti regulatory response indirectly protects the cardiovascular system. The research conducted by Bo Ahr é n's team has demonstrated that liraglutidum reduces glucagon and adrenaline levels at 3.5 mmol/L hypoglycemia, but maintains a counter regulatory response at 2.8 mmol/L severe hypoglycemia. This means that Lixilalai will not "close" the body's last line of defense against severe hypoglycemia, indirectly reducing the risk of cardiovascular events caused by severe hypoglycemia.