Summary of recent progress in the field of diabetes research (03.28)
March 28, 2018 Source: WuXi PharmaTech
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];1. Novo Nordisk Diabetes New Drug Ozempic Approved in Japan
Novo Nordisk recently announced that the Japanese Ministry of Health has approved Ozempic® (semaglutide, somaglutide) for the treatment of adult patients with type 2 diabetes. Ozempic is a new diabetes drug that is produced once a week by Novo Nordisk.
It is estimated that there are more than 415 million people with diabetes worldwide, and about a quarter of them are in China. Insulin resistance occurs in patients with type 2 diabetes, so insulin alone does not work well. It is also necessary to control blood sugar with other hypoglycemic agents. Human glucagon-like peptide-1 (GLP-1) is a hormone secreted by small intestinal cells that promotes insulin secretion and inhibits glucagon secretion after eating to accelerate glucose metabolism and delay gastric emptying. Suppress appetite. Ozempic is an analog of human natural GLP-1 that stimulates insulin production in a glucose-dependent manner, inhibits glucagon secretion, and reduces appetite and food intake. Previous data shows that Ozempic has a lower risk of hypoglycemia and has an advantage in helping patients lose weight.
The approval of Ozempic in Japan was based on the results of the clinical trial “SUSTAINâ€, which included more than 8,000 adult patients with type 2 diabetes from multiple centers, of which approximately 1,200 were from Japan. The results showed that the glycosylated hemoglobin (HbA1c) was significantly reduced by Ozempic treatment compared to the other treatments in the control group, and the average body weight of the subjects using Ozempic was used in two SUSTAIN monotherapy trials. The reduction of the agent is more.
Dr. Mads Krogsgaard Thomsen, Executive Vice President and Chief Scientific Officer of Novo Nordisk, said: "We are very excited about Ozempic's approval in Japan, which provides a new effective treatment for millions of people with type 2 diabetes to help Treat this complex disease."
2. Liver-made enzymes promote abdominal fat inflammation and diabetes risk
According to the World Health Organization (WHO), the world's obese population has reached 40%. Obesity is closely related to some diseases, such as abdominal fat, which increases the risk of type 2 diabetes and insulin resistance. Abdominal fat inflammation can be dangerous, but the cause of inflammation has not been fully elucidated. Recently, a new study by the Columbia University Irving Medical Center showed that an enzyme from the liver can cause inflammation of the fat. Related papers have been published online in Nature.
The researchers found that an enzyme called DPP4 in the liver of obese mice increased expression. This enzyme promotes the activation of inflammatory cells after entering the abdominal adipose tissue through the blood. The good news is that shutting down DPP4 production in the liver can alleviate this fat inflammation. The mouse model showed that the closure of DPP4 alleviated the inflammatory state of abdominal fat, and even though the animals were still obese, their insulin resistance improved.
â–²Image source 123RF
Although there are unpublished data indicating that this pathway is also present in humans, existing DPP4 inhibitors are not effective in relieving fat inflammation. There are many patients with type 2 diabetes who take oral DPP4 inhibitors (gliptins) to help control their condition. These drugs lower blood sugar by preventing DPP4 from acting as a hormone that stimulates insulin production. But the researchers found that these drugs had no effect on the inflammation of abdominal fat in obese mice. The researchers believe that this may be related to the role of this type of DPP4 inhibitor in the intestines and liver: this type of DPP4 inhibitor lowers blood glucose by inhibiting DPP4 in the intestine, but evidence suggests that DPP4 inhibitors in the intestine will eventually Promotes an inflammatory response in fat, thereby counteracting the anti-inflammatory effects that may occur when drugs reach inflammatory cells. When researchers selectively block DPP4 production in hepatocytes, they can reduce fat inflammation, improve insulin resistance, and lower blood sugar. These findings suggest that if the DPP4 inhibitor can be redirected to the liver cells and away from the gut, the effect may be better.
"If we can develop a method that targets liver DPP4, it has the potential to be a powerful new method for the treatment of obesity-induced type 2 diabetes," said Dr. Ira Tabas, a professor at Columbia University School of Medicine. At least in our preclinical models, it has been shown that specific inhibition of DPP4 in hepatocytes can counter the core problem of type 2 diabetes, namely insulin resistance."
3. AstraZeneca announced the clinical positive results of the new phase 2 diabetes drug
AstraZeneca recently announced the positive results of Phase 3 clinical trial DERIVE, which evaluated the efficacy of FARXIGA (dapagliflozin, dapagliflozin) in patients with type 2 diabetes mellitus with moderate renal insufficiency (stage 3A chronic kidney disease) And security. FARXIGA is a SGLT2 inhibitor that can be used as an adjunct to diet and exercise to help people with type 2 diabetes control their blood sugar.
According to the US Centers for Disease Control and Prevention, there are 30.3 million people with diabetes in the United States, with type 2 diabetes accounting for 90% to 95% of all people with diabetes. In the United States, type 2 diabetes is the leading cause of chronic kidney disease, affecting more than 40% of patients.
The DERIVE trial will enroll 321 type 2 diabetes (glycated hemoglobin [HbA1c] 7-11%, mean 8.2%) and stage 3A chronic kidney disease (average estimated glomerular filtration rate [eGFR] 53 mL/min/) from 8 countries. 1.73 m2) patients were randomized to receive either 10 mg of dapagliflozin or placebo, and the study achieved primary and secondary efficacy endpoints. Studies have shown that from baseline to week 24, the 10 mg dose of dapagliflozin significantly reduced multiple markers of type 2 diabetes and chronic kidney disease, including mean HbA1c (-0.37%) (with consolation) compared with placebo. Differences - 0.34%, p < 0.001), mean body weight (-3.17 kg) (difference - 1.25 kg, p < 0.001), fasting blood glucose (-21.46 mg / dL) (difference -16.6 mg / dL, p = 0.001) Mean systolic blood pressure (-4.8 mmHg) (difference -3.1 mmHg, p <0.05) and mean eGFR (-3.23 mL/min/1.73 m2) (difference [95% CI]: -2.60 mL/min/1.73 m2 [- 5.03 vs -0.16]). Treatment-related adverse events were 10.6% and 6.2% in the dapagliflozin and placebo groups, respectively. The most common adverse events included urinary tract infections and frequent urination, with no reports of fractures or amputations. DERIVE added important information to previous studies of patients with type 2 diabetes and moderate renal impairment.
Dr. Jim McDermott, Vice President, Medical Affairs, AstraZeneca Diabetes, said: "We are committed to helping patients with complex type 2 diabetes and chronic kidney disease through a wide range of research and treatments for cardiovascular diseases, kidneys and metabolism. DERIVE Study Will help us learn more and provide more data on FARXIGA in patients with type 2 diabetes."
Reference materials:
[1] Ozempic® approved in Japan for the treatment of type 2 diabetes
[2] Belly fat promotes diabetes under orders from liver
[3] AstraZeneca Presents New Data Evaluating Safety and Efficacy of FARXIGA in Patients with Type 2 Diabetes and Moderate Renal Impairment
Original Title: Summary of Recent Progress in Diabetes Research (No. 55)
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