According to statistics from the World Health Organization, the number of obesity patients worldwide has nearly tripled since 1975, with over 1.9 billion adults overweight. Obesity is associated with increased risk of many diseases, such as type 2 diabetes, cancer, cardiovascular disease, etc. However, in history, effective treatments for weight loss are very limited. Most weight loss pills not only have poor effects, but also have serious side effects.
However, with the investment of biopharmaceutical and technology companies in this field, a new generation of weight loss therapies is constantly emerging in recent years. They are called peptides, originally a substance extracted from organisms, microorganisms, and plants. After being transformed by scientists, they can be synthesized in the laboratory to treat various diseases of the human body, such as cancer, hyperglycemia, osteoporosis ,obesity etc.
At present, many biological companies can complete the synthesis of peptide drugs by using custom peptide synthesis & peptide solid-phase technology to to assist pharmaceutical companies in the development of peptide API drugs.
Table of Contents:
1. The bumpy history of weight loss drug development
2. The emergence of weight loss peptide drugs: Semaglutide
3. Liraglutide is a safe and effective drug for treating obesity
4. Weight loss evaluation of exenatide
5. Comparison of weight loss effects of dulaglutide and benaglutide
1. The bumpy history of weight loss drug development
The history of weight loss drug development is full of twists and turns. As early as the 1930s, 2,4-dinitrophenol (DNP) became one of the first compounds used for weight loss. It is a mitochondrial uncoupling drug that can interfere with the body’s chemical reactions that generate and store energy, allowing energy to be released in the form of heat, thereby reducing weight. However, it can also cause the body’s temperature to rise uncontrollably.
In the 1960s, the weight loss drugs approved by the US FDA were all derivatives of amphetamine (amphetamine), which played a role in suppressing appetite, but these drugs were addictive and could lead to dangerous high blood pressure. Although they may reduce weight by 5-10%, they cannot be taken for a long time. Many of the drugs approved by the FDA since the 1990s have been delisted due to toxic side effects, and once stopped, patients’ weight usually rebounds, which is not satisfactory for patients.
2. The emergence of weight loss peptide drugs: Semaglutide
In June 2014, the US FDA approved Wegovy (semaglutide) developed by Novo Nordisk Nordisk to be marketed for long-term treatment of obese patients. This is the first new drug approved by the US FDA for use in patients with general obesity or overweight since 2014, and represents the achievement of the development of a new generation of weight loss drugs.
Wegovy belongs to a group of drugs called glucagon like peptide 1 (GLP-1) receptor agonists. It simulates the function of GLP-1, a hormone secreted by the gastrointestinal tract that plays a role in regulating blood sugar. Almost all approved GLP-1 receptor agonists can also cause weight loss when treating patients with diabetes. In clinical trials targeting ordinary obesity patients, Wegovy achieved excellent weight loss results, combined with lifestyle changes, resulting in an average weight loss of over 15% in patients, while the control group only lost 2.5% of their weight.
At present, many biomedical and technology companies are developing innovative therapies for these hormone signaling pathways. For example, the combination of Novo Nordisk’s amylin analog caglinitide and smeglutide has achieved positive weight loss results in the Phase I clinical trial. It is currently undergoing testing in Phase 2 clinical trials.
3. Liraglutide is a safe and effective drug for treating obesity
Liraglutide is a glucagon like peptide (GLP) – 1 analog, which acts on islets in a glucose dependent manner β ，It can promote the synthesis and secretion of insulin and reduce the blood sugar level of the body. It is a therapeutic drug for type 2 diabetes (T2DM).
On December 23, 2014, Liraglutide was approved by the US Food and Drug Administration (FDA) for the treatment of adult overweight and obesity （with a body mass index (BMI) of ≥ 30 kg · m-2, or BMI of ≥ 27 kg · m-2 and at least one obesity complication such as T2DM, hypertension, etc.）. It is now widely used for weight control in the United States and the European Union.
While not affecting the pleasure of eating in obese people, liraglutide can enhance patients’ sensitivity to sweet and bitter tastes, change people’s taste, and reduce obese people’s craving for fatty food, thereby achieving weight loss. In addition, liraglutide can promote the transformation of white adipose tissue (WAT) into brown adipose tissue (BAT), increase heat production and reduce visceral fat content, and reduce fat in BAT and WAT Drop content, reduce body weight
Liraglutide has a long half-life, which can prolong the absorption time at the subcutaneous injection site, improve the efficacy of liraglutide monomer, and realize subcutaneous administration once a day. Studies have found that liraglutide can reduce the subcutaneous fat tissue and abdominal visceral fat tissue in obese people, effectively control the weight of obese people, and reduce the BMI of obese people. It is a safe and effective drug for treating obesity
4. Weight loss evaluation of exenatide
Exenatide was originally a bioactive peptide extracted from the salivary glands of the American scorpion, consisting of 39 amino acids. Developed jointly by Amylin and Lilly Pharmaceuticals in the United States, it is mainly used for T2DM patients who cannot effectively control blood sugar with metformin or sulfonylurea hypoglycemic drugs. Exenatide was launched in the United States in 2005.
Exenatide is a GLP-1 receptor agonist, which is mainly used in the treatment of type 2 diabetes. In addition to regulating blood glucose and insulin function, it can also reduce the body mass of patients. Basic research suggests that exenatide may also have anti-inflammatory and antioxidant effects
Like liraglutide, exenatide has a significant weight reduction effect on overweight and obese type 2 diabetes patients. At present, exenatide is only recommended for obese patients with type 2 diabetes, not for simple obesity.
5. Comparison of weight loss effects of dulaglutide and benaglutide
Dulaglutide is a new long-acting agonist. Its relatively large molecular weight can delay subcutaneous absorption and renal filtration clearance, so the half-life is about 30 h, and it can achieve long-acting effects of subcutaneous injection once a week. Benaglutide is a fully human amino acid sequence, which is quickly absorbed into the blood after subcutaneous injection, and has a relatively high distribution in the excretory system. short.
Liraglutide, dulaglutide, and benaglutide can all effectively lower blood sugar, increase TIR, protect islet function, and reduce urinary microalbumin; after dulaglutide treatment, TIR improved most obviously, suggesting that it has better Stabilize the hypoglycemic effect, reduce blood sugar fluctuations, thereby delaying the occurrence and development of early diabetic nephropathy; benaglutide has stronger postprandial blood sugar control and weight loss, but has a high incidence of gastrointestinal reactions