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*Only for medical professionals to read and refer to the new development of hypoglycemic drugs, come to understand! This year is one hundred years of the discovery of insulin.
Its discovery has saved the lives of countless people with diabetes (especially type 1 diabetes), making diabetes from an incurable disease to an important chronic disease
.
However, the variety of oral hypoglycemic drugs was very limited for a long period of time during this century, and new drugs did not continue to appear until the 1990s
.
So what are the new developments of hypoglycemic drugs in the past 30 years? Recently, at the "Peking University Endocrinology and Metabolic Diseases and Reproductive Health Symposium", Professor Hong Tianpei from the Department of Endocrinology, Peking University Third Hospital gave you a detailed analysis of the latest developments! Progress 1: The emergence of a large number of new drugs.
Why did new drugs continue to emerge until the 1990s? Professor Hong pointed out that both the UK Prospective Study on Diabetes (UKPDS) and the Progressive Diabetes Outcome Trial (ADOPT) have shown that monotherapy of traditional oral hypoglycemic drugs and insulin has not been able to control the blood sugar of patients with type 2 diabetes (T2DM) Maintain long-term stability and compliance
.
In the face of this unmet clinical need, everyone has gradually gained more understanding of the pathophysiology of diabetes, from the past trio to the current octet, especially in the reduction of incretin effect and renal glucose In these two links of increased sugar reabsorption, researchers have found a breakthrough in the development of new drugs
.
In recent years, secretin drugs and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have sprung up (Figure 1)
.
Figure 1 New types of hypoglycemic drugs marketed in China in recent years.
Moreover, the research and development of new drugs targeting the glucagon-like peptide-1 (GLP-1) target is still under continuous exploration, except for GLP-1 receptor agonists ( In addition to GLP-1 RA) injection preparations, future research and development directions include oral peptides GLP-1 RA, oral small molecule compounds GLP-1 RA, GLP-1 and gastric inhibitory peptide (GIP) dual receptor agonists, GLP-1 glucagon and double receptor agonist acting on the intestinal L cells to GLP-1 secretagogue or the like
.
Progress 2: The emergence of cardiovascular outcome research // Why do new-type hypoglycemic drugs need to conduct cardiovascular outcome research? The CAPUTRE study conducted in early 2019 showed that about one-third of T2DM patients have cardiovascular disease, and the vast majority are atherosclerotic cardiovascular disease (ASCVD)
.
The 23-year follow-up data of the China Daqing study found that about half of Chinese diabetic patients died of cardiovascular disease
.
Therefore, in patients with T2DM, cardiovascular disease is the most important comorbidity and cause of death
.
In addition, the 2007 "rosiglitazone storm" gave rise to concerns about the cardiovascular safety of new-type hypoglycemic drugs
.
Therefore, the U.
S.
Food and Drug Administration (FDA) proposed new management practices the following year, requiring that all phase II/III studies include high-risk populations of cardiovascular disease and conduct a meta-analysis before submitting applications for new-type hypoglycemic drugs.
, To assess the cardiovascular risk between the study group and the control group
.
Listing needs to achieve superiority or non-inferiority.
The upper limit of 95% CI for non-inferiority cannot exceed 1.
8.
If it is between 1.
3 and 1.
8, a cardiovascular outcome study (CVOT) needs to be supplemented after marketing (Figure 2)
.
This is why there are so many CVOT studies now
.
Figure 2 FDA regulations regarding the criteria for determining the impact of new hypoglycemic drugs on cardiovascular outcomes // 2 pictures summarizing the latest progress in research on cardiovascular/renal outcomes of hypoglycemic drugs! Up to now, three new types of hypoglycemic drugs have different performances in cardiovascular/renal outcome studies: ● Dipeptidyl peptidase 4 (DPP-4) inhibitors have not been studied in CVOT except for vildagliptin, saxagliptin, CVOT studies of alogliptin, sitagliptin and linagliptin showed that the primary adverse cardiovascular events (MACE) were all neutral results; ● CVOT studies of some GLP-1 RA showed that it could significantly reduce the first grade End-point MACE risk, heart failure risk has not been significantly reduced, and renal composite end-point event risk has been reduced, but there is a lack of evidence for hard end-points, so Professor Hong believes that it needs to be further explored in future studies; ● SGLT-2 inhibitors are decreasing by one level There are differences between different drugs in the end-point MACE risk, but there is a good consistency in the risk of heart failure hospitalization and the risk of renal complex events
.
In order to understand the characteristics of each drug more clearly and intuitively, Professor Hong summarized the results in two charts (Figure 3-4)
.
Figure 3 Summary of cardiovascular endpoints of new-type hypoglycemic drugs Figure 4 Summary of renal-related clinical endpoints of new-type hypoglycemic drugs With the continuous increase of diabetes treatment drugs and the continuous enrichment of evidence-based evidence, what kind of window has been opened for the treatment of diabetes Woolen cloth? ● The 2019 ADA/EASD expert consensus recommends that for T2DM patients with ASCVD or high-risk factors, heart failure (HF) or chronic kidney disease (CKD), priority should be given to GLP-1 RA or SGLT-2 inhibition with evidence of cardiovascular and renal protection It should be considered independently of baseline glycosylated hemoglobin (HbA1c) levels or individualized HbA1c goals to improve the patient’s heart and kidney clinical outcomes
.
● The 2020 "Expert Consensus on the Clinical Application of Hypoglycemic Drugs in Patients with Type 2 Diabetes and Heart and Kidney Diseases in China" and the "Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2020 Edition)" also recommend that regardless of the baseline HbA1c level and individualized HbA1c control goals Whether it is up to standard, T2DM patients with ASCVD or high-risk factors, HF or CKD, should be given priority in combination with GLP-1RA or SGLT2 inhibitors with evidence of cardiovascular and renal benefits
.
// With the update of the guideline recommendations, a voice began to appear-"Can new hypoglycemic drugs completely replace metformin in the T2DM treatment path?" In this regard, Professor Hong believes that whether it is for organ protection and blood sugar control to maintain long-term In terms of stable compliance or comprehensive metabolic control (including blood sugar, blood pressure, and blood lipids), there is still a lack of research evidence on the head-to-head comparison of GLP-1 RA or SGLT2 inhibitors and metformin
.
Therefore, he believes that it is still too early to kick metformin out of the center of the stage
.
In the end, Professor Hong emphasized that both blood sugar reduction standards and improvement of heart and kidney clinical outcomes must be both hard, and we should not consider one or the other to help us in the overall management of T2DM patients
.
In addition, while treating with hypoglycemic drugs, attention should be paid to the comprehensive management of cardiovascular risk factors such as hypertension, dyslipidemia, and obesity
.
Note: The pictures and content are from the sharing of Professor Hong Tianpei in the "Peking University Endocrine Metabolic Diseases and Reproductive Health Symposium"
.
Expert profile Professor Hong Tianpei, Director of the Endocrinology Department of Peking University Third Hospital, second-level professor, chief physician, and doctoral supervisor, Chairman of the Diabetes Branch of the Beijing Medical Association (seventh) Director of the Endocrinology Branch of the Beijing Medical Association (seventh) Member, Vice Chairman of the Endocrinology Branch of the Chinese Medical Association and Leader of the Diabetes Group, Vice Chairman of the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, Deputy Editor-in-Chief of 6 journals including Chinese Journal of Diabetes, Chinese Journal of Endocrinology and Metabolism, BMJ, Diabetes Care, etc.
Reviewer of SCI journals
Its discovery has saved the lives of countless people with diabetes (especially type 1 diabetes), making diabetes from an incurable disease to an important chronic disease
.
However, the variety of oral hypoglycemic drugs was very limited for a long period of time during this century, and new drugs did not continue to appear until the 1990s
.
So what are the new developments of hypoglycemic drugs in the past 30 years? Recently, at the "Peking University Endocrinology and Metabolic Diseases and Reproductive Health Symposium", Professor Hong Tianpei from the Department of Endocrinology, Peking University Third Hospital gave you a detailed analysis of the latest developments! Progress 1: The emergence of a large number of new drugs.
Why did new drugs continue to emerge until the 1990s? Professor Hong pointed out that both the UK Prospective Study on Diabetes (UKPDS) and the Progressive Diabetes Outcome Trial (ADOPT) have shown that monotherapy of traditional oral hypoglycemic drugs and insulin has not been able to control the blood sugar of patients with type 2 diabetes (T2DM) Maintain long-term stability and compliance
.
In the face of this unmet clinical need, everyone has gradually gained more understanding of the pathophysiology of diabetes, from the past trio to the current octet, especially in the reduction of incretin effect and renal glucose In these two links of increased sugar reabsorption, researchers have found a breakthrough in the development of new drugs
.
In recent years, secretin drugs and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have sprung up (Figure 1)
.
Figure 1 New types of hypoglycemic drugs marketed in China in recent years.
Moreover, the research and development of new drugs targeting the glucagon-like peptide-1 (GLP-1) target is still under continuous exploration, except for GLP-1 receptor agonists ( In addition to GLP-1 RA) injection preparations, future research and development directions include oral peptides GLP-1 RA, oral small molecule compounds GLP-1 RA, GLP-1 and gastric inhibitory peptide (GIP) dual receptor agonists, GLP-1 glucagon and double receptor agonist acting on the intestinal L cells to GLP-1 secretagogue or the like
.
Progress 2: The emergence of cardiovascular outcome research // Why do new-type hypoglycemic drugs need to conduct cardiovascular outcome research? The CAPUTRE study conducted in early 2019 showed that about one-third of T2DM patients have cardiovascular disease, and the vast majority are atherosclerotic cardiovascular disease (ASCVD)
.
The 23-year follow-up data of the China Daqing study found that about half of Chinese diabetic patients died of cardiovascular disease
.
Therefore, in patients with T2DM, cardiovascular disease is the most important comorbidity and cause of death
.
In addition, the 2007 "rosiglitazone storm" gave rise to concerns about the cardiovascular safety of new-type hypoglycemic drugs
.
Therefore, the U.
S.
Food and Drug Administration (FDA) proposed new management practices the following year, requiring that all phase II/III studies include high-risk populations of cardiovascular disease and conduct a meta-analysis before submitting applications for new-type hypoglycemic drugs.
, To assess the cardiovascular risk between the study group and the control group
.
Listing needs to achieve superiority or non-inferiority.
The upper limit of 95% CI for non-inferiority cannot exceed 1.
8.
If it is between 1.
3 and 1.
8, a cardiovascular outcome study (CVOT) needs to be supplemented after marketing (Figure 2)
.
This is why there are so many CVOT studies now
.
Figure 2 FDA regulations regarding the criteria for determining the impact of new hypoglycemic drugs on cardiovascular outcomes // 2 pictures summarizing the latest progress in research on cardiovascular/renal outcomes of hypoglycemic drugs! Up to now, three new types of hypoglycemic drugs have different performances in cardiovascular/renal outcome studies: ● Dipeptidyl peptidase 4 (DPP-4) inhibitors have not been studied in CVOT except for vildagliptin, saxagliptin, CVOT studies of alogliptin, sitagliptin and linagliptin showed that the primary adverse cardiovascular events (MACE) were all neutral results; ● CVOT studies of some GLP-1 RA showed that it could significantly reduce the first grade End-point MACE risk, heart failure risk has not been significantly reduced, and renal composite end-point event risk has been reduced, but there is a lack of evidence for hard end-points, so Professor Hong believes that it needs to be further explored in future studies; ● SGLT-2 inhibitors are decreasing by one level There are differences between different drugs in the end-point MACE risk, but there is a good consistency in the risk of heart failure hospitalization and the risk of renal complex events
.
In order to understand the characteristics of each drug more clearly and intuitively, Professor Hong summarized the results in two charts (Figure 3-4)
.
Figure 3 Summary of cardiovascular endpoints of new-type hypoglycemic drugs Figure 4 Summary of renal-related clinical endpoints of new-type hypoglycemic drugs With the continuous increase of diabetes treatment drugs and the continuous enrichment of evidence-based evidence, what kind of window has been opened for the treatment of diabetes Woolen cloth? ● The 2019 ADA/EASD expert consensus recommends that for T2DM patients with ASCVD or high-risk factors, heart failure (HF) or chronic kidney disease (CKD), priority should be given to GLP-1 RA or SGLT-2 inhibition with evidence of cardiovascular and renal protection It should be considered independently of baseline glycosylated hemoglobin (HbA1c) levels or individualized HbA1c goals to improve the patient’s heart and kidney clinical outcomes
.
● The 2020 "Expert Consensus on the Clinical Application of Hypoglycemic Drugs in Patients with Type 2 Diabetes and Heart and Kidney Diseases in China" and the "Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2020 Edition)" also recommend that regardless of the baseline HbA1c level and individualized HbA1c control goals Whether it is up to standard, T2DM patients with ASCVD or high-risk factors, HF or CKD, should be given priority in combination with GLP-1RA or SGLT2 inhibitors with evidence of cardiovascular and renal benefits
.
// With the update of the guideline recommendations, a voice began to appear-"Can new hypoglycemic drugs completely replace metformin in the T2DM treatment path?" In this regard, Professor Hong believes that whether it is for organ protection and blood sugar control to maintain long-term In terms of stable compliance or comprehensive metabolic control (including blood sugar, blood pressure, and blood lipids), there is still a lack of research evidence on the head-to-head comparison of GLP-1 RA or SGLT2 inhibitors and metformin
.
Therefore, he believes that it is still too early to kick metformin out of the center of the stage
.
In the end, Professor Hong emphasized that both blood sugar reduction standards and improvement of heart and kidney clinical outcomes must be both hard, and we should not consider one or the other to help us in the overall management of T2DM patients
.
In addition, while treating with hypoglycemic drugs, attention should be paid to the comprehensive management of cardiovascular risk factors such as hypertension, dyslipidemia, and obesity
.
Note: The pictures and content are from the sharing of Professor Hong Tianpei in the "Peking University Endocrine Metabolic Diseases and Reproductive Health Symposium"
.
Expert profile Professor Hong Tianpei, Director of the Endocrinology Department of Peking University Third Hospital, second-level professor, chief physician, and doctoral supervisor, Chairman of the Diabetes Branch of the Beijing Medical Association (seventh) Director of the Endocrinology Branch of the Beijing Medical Association (seventh) Member, Vice Chairman of the Endocrinology Branch of the Chinese Medical Association and Leader of the Diabetes Group, Vice Chairman of the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, Deputy Editor-in-Chief of 6 journals including Chinese Journal of Diabetes, Chinese Journal of Endocrinology and Metabolism, BMJ, Diabetes Care, etc.
Reviewer of SCI journals
