Analysis of progress in the development of global obesity drugs.

Recently, due to the emergence of the new crown epidemic, during the Spring Festival, most parts of the country into a level of emergency response, closed management, all over the country to return to work time many times delayed.
many friends have reflected that after such a long stay at home, the pants before can not be worn.
staying sedentary at home, lacking outdoor exercise, and consuming calories in three meals a day are inevitable, and increasing people's risk of obesity.
will cover how to prevent obesity effectively and provide a review of commonly used therapeutic drugs and research varieties.
Obesity Epidemiology WHO lists obesity as one of the top ten chronic diseases.
obesity and high blood pressure, hyperlipidemia, high blood sugar and called the "death quartet" may be the number one killer of the 21st century.
at least 2.8 million people die each year from being overweight or obese.
obesity was once associated with high-income countries and is now common in low- and middle-income countries.
the number of people with diabetes, hypertension, cardiovascular diseases and other diseases caused by overweight and obesity is increasing year by year and is becoming younger.
Global Morbidity Almost Triples since 1975, according to WHO data.
more than 1.9 billion adults over the age of 18 were overweight in 2016, of whom more than 650 million were obese.
2016, 39 percent of adults 18 and older worldwide were overweight and 13 percent were obese.
340 million children and adolescents aged 5-19 worldwide are overweight or obese.
of obesity in countries around the world from 1975 to 2016 can be found on the WHO's official data website.
1 World Obesity Distribution Source: WHO Database Chart Shows that the world's most obese regions include the United States and Mediterranean countries such as Iraq, Turkey, Egypt, Libya and other countries.
The U.S. obesity prevalence rate was 39.8 percent in 2015-16, affecting about 93.3 million U.S. adults, according to the Centers for Disease Control and Prevention.
China's prevalence of obesity, the prevalence rate in China was about 6.2% in 2016.
in addition, the 2016 Lancet published the Global Adult Weight Survey.
survey found that the world's adult obesity population has overtaken the healthy, and China overtook the United States to become the world's most obese country.
, China has 43.2 million obese men and 46.4 million women, ranking first in the world.
, about 100 million people in China are currently obese.
statistics in the past three years, there is still a lack of a large-scale authoritative epidemiological survey of obesity.
china Health and Nutrition Survey (CHNS) data show that in the 17 years from 1993 to 2009, the prevalence of overweight/obesity among adults increased from 13.4% to 26.4%, an overall linear increase;
According to the 2014 National Physical Monitoring Bulletin issued by the State General Administration of Sports and the Ministry of Education, although the overall level of national physical fitness in China has increased, overweight and obesity are still growing in both the young student population and the adult and elderly populations.
if the BMI value "24" is the limit of overweight, the BMI value "28" is the limit of obesity, the national physical fitness monitoring of the overweight rate and obesity rate of each population as shown in the figure.
Figure 2 2010 and 2014 Adult and Senior Overweight Rate and Obesity Rate Figure 3 Obesity Rates for Adolescents (16-18 Years) in Different Regions 2010 and 2014 Source: 2014 National Physical Fitness Bulletin The Prevention of Obesity Should Run through Daily Life, divided into diet, exercise, psychology and lifestyle adjustments.
Diet Limit energy intake so that it is below consumption.
ensure a balanced diet, eat more fruits and vegetables, avoid excessive consumption of carbohydrates and high-fat foods, avoid fried foods.
develop a scientific and healthy diet, regular quantitative diet, eat less and eat more.
exercise, appropriate exercise plans combined with a reasonable diet, and long-term adherence, can effectively prevent obesity.
in accordance with their own actual situation, under the guidance of professionals to choose the right mode of exercise and the amount of exercise, pay attention to step by step.
psychological guidance during weight loss pay attention to their own mental state, if necessary, can seek help from a professional doctor for psychological guidance.
way of life develop good habits and avoid staying up late.
Therapeutic drugs and market conditions Obesity clinical treatment drugs according to the mechanism of action can be divided into three categories: central appetite suppression drugs appetite by the inner part of the lower cerebrocephalus satiet and the outer part of the lower cerebrocephalus feeding center regulation.
two long-acting diet pills have been discontinued: Limonaban and Sibutramin, which have been withdrawn from the world because of their increased risk of mental and vascular disease.
amperelavone as an oral anorexia drug approved by the FDA for short-term treatment of obesity, but has not been recommended by the guidelines.
other central appetite-suppressing drugs include 5-HT2C receptor agonists, melanin-concentrated hormone receptor 1 (MCHR1) antagonists and other new drugs as weight loss drugs have entered the clinical trial stage, but no large sample studies.
the gastrointestinal hormone gastrointestinal hypoglycemia, which regulates appetite, is a family of hormones produced by the intestines that work in synergy with other hormones to enhance the role of insulin release in glucose stimulation, and some of the gut glycemics affect ingestions, such as glucagon-like peptides 1 (GLP-1) and gastroprogenial conditioners (OXM).
GLP-1 is synthesized secreted by intestinal L cells, due to the inactivation of DPP-IV, its half-life is only 1-2 minutes, while the GLP-1 similar compound half-life is significantly extended, GLP-1 similarity Exenatide, Liraglutide as a treatment for type 2 diabetes has been listed, in addition to good blood sugar control, in patients with type 2 diabetes can be observed after different degrees of weight loss.
in addition, amylin is secreted by islet beta cells, and its analogue pramlintide was introduced in the United States in 2005 as an affiliate dissonative drug for insulin therapy for diabetes, in addition to improving blood sugar and reducing insulin use, pramlintide has been shown to be an appropriate weight reduction, and no changes in blood pressure have been detected, and hypoglycemia has not been detected.
drugs that act on peripheral tissues And drugs such drugs target two specific targets: first, to reduce fat absorption lipase inhibitors and sodium-glucose co-transporters in the gastrointestinal tract;
lipase inhibitors reduce fat absorption in the diet by inhibiting lipase in the gastrointestinal tract and pancreas.
orlistat is currently the only long-acting weight loss drug on the market.
second-generation drug Cetilistat, a new type of lipid-based benzodiazepine derivative, was approved by the FDA in 2013 and is not yet available in China. the
Sodium-Glucose Co-Transporter (SGLTs) enables active transport of glucose inverse concentration gradients, accompanied by the downward transport of Na-plus concentration gradients, with two sub-types: SGLT1 and SGLT2, which are more suitable as targets for treatment, and SGLT2 inhibitors are a new direction in the development of diabetes drugs.
table below is the drugs currently approved for the treatment of obesity.
1 Currently approved drugs for obesity Description: This list does not contain post-market drugs.
data source: Drug Watanabe's consulting team shows that there are currently seven drugs approved to treat obesity worldwide.
, in fact, several drugs have historically been withdrawn from the market due to severe adverse reactions.
according to the latest news, chloroform hydrochloride (traded as Belvyq®) was withdrawn from the U.S. market in February 2020 because it could lead to an increased risk of cancer in drug users.
addition, the drugs that have been withdrawn from the market include siproumin, limonaban, fenflolamin, phenylpropylamine, etc.
siblemine can cause an increase in cardiovascular disease, while Limonaban can lead to depression and suicide risk; in 1997, the FDA ruled that fentanluamine causes severe damage to the heart valve, revoked its listing license to produce fentanaprene in the United States. Pharmaceutical companies have paid up to $890 million in compensation to patients with heart damage, and in 2001, CFDA (now NMPA) stopped selling and using the appetite inhibitor amphetamine, which was found to cause severe consequences such as hemorrhagic stroke.
at present, most of the drugs in the market for many years of old drugs, in recent years there is no new mechanism of the role of innovative drugs approved for market.
domestic, only Oris he was approved for listing.
by the above analysis can be seen, with the increasingly severe incidence of obesity is in sharp contrast to the depressed weight loss drug market, although foreign guidelines are drug treatment as an important aid to weight control and management, but in recent years, most of the listed weight loss drugs market performance flat, or even encounter withdrawal.
clinical in-study varieties will be clinically used to treat obesity in the study of drugs collated as shown in the table below.
Table 2 Obesity Clinical Species As shown in the table above, there are currently 38 drugs in the study worldwide for the treatment of obesity, most of which are in clinical Phase I-II, and only three drugs are in Clinical Phase III, respectively, Setmelanotide, Tirzepatide and Beinaglutide.
Setmelanotide is a proliferative peptide meldonic pinot-4 receptor (MC4R) agonative developed by Rhythm for rare genetic obesity, including leptin receptor (LEPR) defective type and POMC defective obesity, which the FDA previously awarded for breakthrough therapy.
Clinical Phase II study data show that the clinical efficacy of the drug is significant, can reduce the transition diet and weight of three LEPR deficiency obesity patients, and the drug tolerance is good, there are no serious adverse events reported.
Tirzepatide, developed by Eli Lilly, is a gastric inhibitor receptor (GIPR) and glutinoid-like peptide (GLP1R) double an agitator used to treat obesity.
Beinaglutide is a recombinant human glucosin peptide-1 (7-36), essentially a intestinal insulin-promoting secretion peptide that promotes the release of glucose-dependent insulin and reduces the secretion of glucoglycoprotein, which has been approved in China to treat type 2 diabetes, a product called Yishengtai ®.
Benalutide, developed by Shanghai Renhui Biopharmaceuticals, is currently developing new indications of obesity in China.
currently, the drug is currently conducting clinical Phase III studies in China to assist in lifestyle interventions to treat overweight/obesity in adults.
, obesity as one of the top ten chronic diseases, can cause diabetes, hypertension, cardiovascular disease, etc. , endangering human health.
the number of obese people in the world is increasing, with nearly 1 billion or more obese patients.
currently has seven drugs approved worldwide to treat obesity, but in the history of weight-loss drugs, several drugs have been withdrawn due to serious adverse reactions, such as the recent withdrawal of chlorpyrifos hydrochloride (the product called Belviq ®) in the United States, due to the possibility of increasing the risk of cancer in patients, The Seido, announced that it was withdrawn from the market and discontinued in the U.S. market.
Despite the large number of weight-loss drugs, there are still 38 clinically active species, three of which are in clinical phase III, namely Setmelanotide, Tirzepatide and Beinaglutide.
although the variety of foreign weight-loss drugs fierce competition, but the domestic weight loss drug market is Olista stand out, and because GLP-1 receptor agonists such as liraglutide and other new weight-loss drugs in the country has not been approved for obesity, so in the short term, Olisthe will still occupy the domestic weight loss drug market dominant position.
References s1: Obesity and Overweight. Prevlance of obesity among adults, ages 18 plus, 1975-2016.Di C M, Bentham J, Stevens G A, et al. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooledanalysis of 1698 population-based measurement studies with 19.2 millionparticipants .J. Lancet, 2016, 387 (10026): 1377. China Health and Nutrition Survey (CHNS) (DB/OL) .The State General Administration of Sports. National Physical Monitoring Bulletin 2014. (The risk of cancer is high! The FDA has asked the drug chloraquesereinn to be withdrawn.Rhythm Presents Positive Initial Data for Setmelan.