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 and is expected to become the first antibody drug for type 1 diabetes

Type 1 diabetes (T1D) is a chronic autoimmune disease, which is caused by the destruction of insulin-producing beta cells in the pancreas. There are about millions of patients worldwide, the most common among children and adolescents. Patients need daily insulin injections to maintain their survival. There are currently no effective interventions 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.

On May 27th, 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.

2. International clinical practice guidelines are released: SGLT-2 inhibitors or GLP-1 receptor agonists are recommended for adult patients with type 2 diabetes

Type 2 diabetes (T2D) is currently the most common metabolic disease. In the past 50 years, the number of patients has continued to increase, and it has shown 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. Unlike type 1 diabetes caused by congenital insufficient insulin secretion, insulin resistance is believed 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 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.

Therefore, on May 11, the "British Medical Journal" published an international clinical practice guide, recommending SGLT-2 inhibitors or GLP-1 receptor agonists for adult type 2 diabetes.

Guide recommendations:

(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 recommendation).

(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 the National Medical Products Administration (NMPA) of China showed that AstraZeneca applied for a clinical trial application for a new class 1 drug, cotadutide injection, and was accepted.

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 binding to its ligand glucagon-like peptide-1 to stimulate insulin secretion, so that postprandial blood glucose is reduced and maintained at a normal level.

In a randomized, double-blind, phase 2a study in patients with type 2 diabetes, it was preliminarily confirmed that its hypoglycemic effect is mediated by enhanced insulin secretion and delayed gastric emptying. More clinical research results show that in overweight patients with type 2 diabetes with fatty liver, cotadutide shows the effect of reducing liver fat levels and reducing liver fibrosis.

4. GLP-1/GIP dual target agonist, Huadong Medicine introduced USD 28 million

On June 2nd, Huadong Medicine announced that it has reached a cooperation with Japanese SCOHIA company, with a US$4 million down payment and a maximum of US$24 million in development, registration and sales milestone payments to obtain GLP-1/GIPR dual target excitement in clinical phase I The exclusive development, production and commercialization rights of the antidiabetic drug SCO-094 in 25 Asia-Pacific countries and regions (excluding Japan) such as China, South Korea and Australia.

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.