1. Type 2 diabetes has ushered in new progress: support for approval, guideline recommendation, introduction authorization...

According to a study published in the British Medical Journal in 2020, the number of diabetic patients in China has exceeded 129.
8 million
.

As a complex and lifelong disease, the high incidence of diabetes complications brings a heavy burden to patients, their families and society
.

 This year marks the 100th anniversary of the discovery of insulin by humans.
For nearly a hundred years, people have been exploring the pathogenesis of diabetes and are committed to providing patients with safe and effective sugar control programs
.

Innovation continues.
Recently, the field of diabetes has once again ushered in a series of new developments
.

1.
Teplizumab was approved by FDA experts with 10:7 votes.
It is expected to become the first antibody drug for type 1 diabetes.
Type 1 diabetes (T1D) is a chronic autoimmune disease caused by the destruction of insulin-producing β cells in the pancreas.
The formed disease
.

There are about millions of patients worldwide, the most common among children and adolescents.
Patients need daily insulin injections to maintain survival.
There is currently no effective intervention to prevent T1D
.

 Teplizumab (PRV-031) is a humanized anti-CD3 monoclonal antibody that can prevent the formation of CD3-TCR complexes, thereby preventing T cells from attacking pancreatic β cells
.

Teplizumab (PRV-031) Mechanism of Action (Source: Reference 1) On May 27, Teplizumab was approved by the FDA Endocrine and Metabolic Drug Advisory Committee (EMDAC) with 10 (for): 7 (against) votes
.

If approved, teplizumab will become the first antibody drug for type 1 diabetes
.

 Clinical efficacy The clinical data published in the New England Journal of Medicine [2] showed that among more than 1,000 patients with type 1 diabetes, more than 800 patients received teplizumab treatment
.

Compared with the placebo group, templizumab can delay the onset of high-risk type I diabetes by more than two years, and can effectively reduce the incidence of high-risk diabetes
.

 Specifically, compared with placebo, a single 14-day course of teplizumab treatment can significantly delay the onset of T1D.
The median time to onset in high-risk children and adults was 48.
4 months, compared with only 24.
4 months in the placebo group
.

During the follow-up period, 72% of the placebo group were diagnosed with type 1 diabetes, while only 43% of the teplizumab group
.

In terms of safety, teplizumab is well tolerated, and the data are consistent with previous studies in newly diagnosed patients
.

 In addition, in the key TN-10 trial [3], compared with placebo, templizumab can delay the onset of disease in patients with insulin-dependent T1D but not yet symptomatic by an average of about 3 years
.

 2.
International clinical practice guidelines are released: Recommend SGLT-2 inhibitors or GLP-1 receptor agonists for adult type 2 diabetes patients with type 2 diabetes (T2D) as the most common metabolic disease, in the past 50 years , The number of patients has continued to increase, and it is showing a trend of spreading from Western countries to Western Pacific countries such as Asia and Africa
.

In addition, according to existing models, it is estimated that by 2045, approximately 700 million people worldwide will be affected by this disease [4]
.

Unlike type 1 diabetes caused by congenital insufficient insulin secretion, insulin resistance is considered to be the main cause of the development of T2D
.

Although there have been many studies on T2D in recent years, the specific pathogenic mechanism is still not very clear until now
.

 Patients with T2D have an increased risk of cardiovascular disease, kidney disease, and other complications
.

With the accumulation of high-quality experimental evidence, the management of type 2 diabetes is shifting from being dominated by blood glucose treatment goals to focusing on both cardiovascular and renal benefits
.

 SGLT-2 (sodium-glucose cotransporter 2) inhibitors and GLP-1 (glucagon-like peptide 1) receptor agonists are two relatively new types of hypoglycemic drugs.
Not only are they used for metformin treatment, the blood glucose level remains In the elevated population, these drugs have the potential to be used for treatment earlier as trials have proved their heart and kidney benefits
.

The mechanism of action of SGLT-2 inhibitors (Source: Reference 5) The pleiotropic mechanism of GLP-1 (Source: Reference 6) Therefore, on May 11, the "British Medical Journal" published an international clinical practice guideline for SGLT -2 inhibitors or GLP-1 receptor agonists are recommended for adults with type 2 diabetes [7]
.

 The guidelines recommend: (1) With ≤3 cardiovascular risk factors, but no CVD (cardiovascular disease) or CKD (chronic kidney disease): It is not recommended to initiate SGLT-2 inhibitors or GLP-1 receptor agonist therapy (weak Recommended)
.

(2)>3 cardiovascular risk factors, but no CVD or CKD: It is recommended to start using SGLT-2 inhibitors (weak recommendation), and it is not recommended to start GLP-1 receptor agonist therapy (weak recommendation)
.

(3) Diagnosed CVD or CKD: It is weakly recommended to start using SGLT-2 inhibitors and GLP-1 receptor agonists
.

(4) Diagnosed CVD and CKD: It is strongly recommended to start using SGLT-2 inhibitors, and it is weakly recommended to start using GLP-1 receptor agonists
.

 Cardiovascular risk factors include: age> 60 years, male, Asian, African or Hispanic, family history of cardiovascular disease or kidney disease, poor control of glycosylated hemoglobin (>6.
5%), smoking, poor control of hypertension ( ＞140/90 mm Hg), dyslipidemia (total cholesterol ≥5.
2 mmol/L)
.

 3.
GCGR/GLP-1R dual agonist clinical trial application was accepted by CDE On May 14, the official website of the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) showed that AstraZeneca applied for a Class 1 new drug cotadutide injection The clinical trial application was accepted and accepted [8]
.

 Cotadutide is a dual agonist of glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R)
.

GCGR and GLP-1R are members of the G protein-coupled receptor family.
They are two important "regulators" for maintaining the balance of human blood sugar: in the state of starvation, GCGR can increase human blood sugar levels by binding to its ligand glucagon ; And GLP-1R mainly plays a role after ingestion, by combining with its ligand glucagon-like peptide-1 to stimulate insulin secretion, so that postprandial blood glucose is reduced and maintained at a normal level
.

Introduction to Cotadutide (Source: AstraZeneca official website) In a randomized, double-blind, phase 2a study for patients with type 2 diabetes, it was preliminarily confirmed that its hypoglycemic effect is mediated by enhanced insulin secretion and delayed gastric emptying.
Guide
.

More clinical research results show that in overweight patients with type 2 diabetes with fatty liver, cotadutide has shown the effect of reducing liver fat levels and reducing liver fibrosis [9]
.

 4.
GLP-1/GIP dual target agonist, Huadong Medicine US$28 million introduction On June 2, Huadong Medicine announced that it has reached a cooperation with Japanese SCOHIA company, with a down payment of 4 million US dollars and a maximum of 24 million US dollars in development, registration and Sales milestone payment obtained the exclusive development, production and production of the GLP-1/GIPR dual target agonist hypoglycemic drug SCO-094 in clinical phase I in 25 Asia-Pacific countries and regions (excluding Japan), including China, South Korea, and Australia.
Commercialization rights [10]
.

 Dual target agonists are biological molecules that specifically bind to two receptors at the same time
.

When combined with the target, it can activate downstream pathways, enhance the biological effect of the target, and simultaneously give play to the advantages of the two targets, which has a dual effect.
It has been a focus of attention in the field of diabetes in recent years
.

 SCO-094 is a specific dual-target agonist that selectively activates GLP-1 receptor and GIP receptor, stimulates downstream pathways, and produces biological effects such as blood sugar control and weight loss
.

Preclinical in vitro studies have shown that SCO-094 has strong target binding activity and cell biological activity
.

The results of drug efficacy in animals show that it has a powerful hypoglycemic effect, weight loss and liver function improvement, lower triglycerides and inhibit liver steatosis
.

 In terms of clinical research, SCO-094 is conducting a randomized, placebo-controlled, double-blind, single-center evaluation of the tolerability, safety, pharmacokinetics and pharmacodynamics of a single subcutaneous administration in patients with type 2 diabetes in the United Kingdom.
Clinical trials
.

In clinical trials, the expected hypoglycemic effect has been observed, and currently all subjects have not experienced hypoglycemia.
This clinical trial is still blind
.

With the development of treatment concepts and the continuous production of innovative drugs, it has become the common goal of diabetes treatment and drug research and development to provide patients with hypoglycemic options that take into account the benefits of cardiovascular metabolism and high compliance
.

It is believed that in the near future, with the further deepening of scientific research and interdisciplinary and cross-border cooperation, the treatment of diabetes, an ancient disease, will fundamentally change
.

 Reference: 1.
https://endpts.
com/fda-adcomm-votes-in-favor-of-approving-provention-bios-drug-to-delay-type-1-diabetes/; 2.
https://doi.
org/10.
1056/NEJMoa1902226; 3.
https://endpts.
com/news-briefing-10-years-later-teplizumab-gets-a-second-shot-at-an-fda-ok-jj-files-for-amivantamab-approval-in-europe/ ; 4.
Cho, NH et al.
IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045.
Diabetes Res.
Clin.
Pract.
138, 271–281 (2018); 5.
Vivian EM.
Drugs Context.
2014 Dec 19; 3212264; 6.
Sussman MA, Völkers M, Fischer K, Bailey B, Cottage CT, Din S, Gude N, Avitabile D, Alvarez R, Sundararaman B, Quijada P, Mason M, Konstandin MH, Malhowski A, Cheng Z, Khan M, McGregor M : Myocardial AKT: the omnipresent nexus.
Physiol Rev.
2011, 91: 1023-1070.
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1152/physrev.
00024.
2010; 7.
Li S, Vandvik PO, Lytvyn L, Guyatt GH, Palmer SC, Rodriguez-Gutierrez R, et al.
, (2021).
SGLT-2 inhibitors or GLP-1 receptor agonists for adults with type 2 diabetes: a clinical practice guideline.
BMJ, doi:10.
1136/bmj.
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Retrieved May 14, 2021 from http://#; 9.
New CVRM: emerging pipeline.
Retrieved March 26, 2021, from https:// 10.
Retrieved June 02, 2021, from https:// mp.
weixin.
qq.
com/s/qGLR1ieXg5nUGSTKDa4QYg.
Yaodu APP "points new game" company enjoys the database over-value privileges Talk: The influence of BCS classification on the solubility, permeability and dissolution of drug substances in the intestines of the human body-mp.
weixin.
qq.
com/s/qGLR1ieXg5nUGSTKDa4QYg.
Hepatic circulation has been up and down for 20 years, where is the future of kinase inhibitors? Click "Read the original text" to keep abreast of industry trends n1091; 8.
Retrieved May 14, 2021 from http://#; 9.
New CVRM: emerging pipeline.
Retrieved March 26, 2021, from https:// 10.
Retrieved June 02, 2021, from https:// mp.
weixin.
qq.
com/s/qGLR1ieXg5nUGSTKDa4QYg.
Yaodu APP "points new game" company enjoys the database over-value privileges Talk: The influence of BCS classification on the solubility, permeability and dissolution of drug substances in the intestines of the human body-mp.
weixin.
qq.
com/s/qGLR1ieXg5nUGSTKDa4QYg.
Hepatic circulation has been up and down for 20 years, where is the future of kinase inhibitors? Click "Read the original text" to keep abreast of industry trends com/s/qGLR1ieXg5nUGSTKDa4QYg.
Yaodu APP "points new game" company enjoys the database over-value privileges Talk: the influence of BCS classification on the solubility, permeability and dissolution of the drug substance The intestinal-hepatic circulation of the drug in the human body Ten years, where is the future of kinase inhibitors? Click "Read the original text" to keep abreast of industry trends com/s/qGLR1ieXg5nUGSTKDa4QYg.
Yaodu APP "points new game" company enjoys the database over-value privileges Talk: the influence of BCS classification on the solubility, permeability and dissolution of the drug substance The intestinal-hepatic circulation of the drug in the human body Ten years, where is the future of kinase inhibitors? Click "Read the original text" to keep abreast of industry trends