This article is reproduced from the U.S. Chinese Medicine Source
[News event]: Today Eli Lilly and BI announced their type 2 diabetes drug, the SGLT2 inhibitor Jardiance, in addition to showing cardiovascular benefits, it also relieves renal dysfunction. This is the secondary endpoint of the prospective clinical trial called EMPA-REG. The primary endpoint of this Phase IV clinical trial involving more than 7,000 people is cardiovascular events. An average of 3.1 years of follow-up showed that Jardiance combined with standard therapies can reduce the risk of myocardial infarction, heart disease death, and stroke compared with placebo. What was announced today in ADA and published in NEJM is the secondary endpoint of this experiment. The use of Jardiance in combination with standard therapies reduced the incidence or worsening of kidney damage by 39% compared with placebo (urinary protein/creatinine ratio>300, creatinine doubled), and more importantly, Jardiance reduced the number of patients starting renal dialysis by 55%. Jardiance became the first hypoglycemic agent to reduce cardiovascular events and alleviate renal dysfunction.
[Drug Source Analysis]: Although this is the first hypoglycemic drug shown to alleviate renal dysfunction, there are a few points to note here. One is that these observations are secondary endpoints of EMPA-REG, not the main observation indicators of the test, and the other is that these renal function indicators are also blood indicators, so the ratio of blood glucose is only the difference between 50 and 100 steps. Delayed renal dialysis is an indicator that has a real impact on patients' lives. Although Jardiance reduces the risk by 55%, the absolute risk is not large, from 0.6% to 0.3%. The main reason is that most of these patients are patients with early kidney injury, and the follow-up time is only 3.1 years. Based on these data, it is unlikely that kidney function will be written into the label.
But this is still an important development. 35% of people with diabetes will eventually have kidney dysfunction, which is a major complication of diabetes. Renal dysfunction is a big market, and it is estimated that 10% of Americans have varying degrees of renal dysfunction. In addition to some traditional antihypertensive drugs, there are no effective drugs to treat renal dysfunction, so new mechanism drugs are an important contribution to this population.
Yesterday it was mentioned that the treatment of diabetes is facing reform, in addition to safe hypoglycemic reduction, the risk of complications must be reduced. Two types of drugs have been shown to improve cardiovascular events, and Jardiance has also been shown to improve renal dysfunction. Although the efficacy of these drugs in improving the prognosis is still relatively slight, this undoubtedly sets a higher standard for future hypoglycemic drugs. Future hypoglycemic drugs may not be enough to reduce blood sugar. This is why Merck recently doubled its safety test into an efficacy test and stopped the development of long-acting DPP4 inhibitors.
In the past, people were not optimistic about SGLT as a hypoglycemic mechanism, and believed that the treatment of diabetes could not only rely on glucouria. Diabetes is indeed not only abnormal blood sugar, but SGLT is unlikely to just inhibit glucose reabsorption. As we learn more about diabetes, diabetes will prove to be a combination of multiple diseases like cancer. In the future, preclinical research requires more complex scientific hypotheses and optimization methods, while clinical development needs to learn from the precision medicine experience of tumors and find the real beneficiaries based on the mechanism markers, not all people with abnormal blood sugar can use them.
