THehira The monster is a venomous lizard from North America, approximately 50 centimeters long and boasting a distinctive fur of black and orange scales. This lethargic reptile, which lives primarily underground and eats only three or four times a year, is behind one of the drug companies’ biggest blockbusters: a new generation of weight loss drugs that has sent patients and investors into a frenzy. It was an unexpected inspiration. Although it was originally created for diabetes, there is growing evidence that it also has benefits for diseases such as the heart, kidneys, and liver.

Since the late 1980s, scientists have discovered glucagon-like peptide-1 (GLP-1) is secreted from the intestines after meals and may be useful in the treatment of diabetes. GLP-1 increases the production of insulin (a hormone that lowers blood sugar levels) and decreases the production of glucagon (which increases blood sugar levels).but GLP-1 is broken down very quickly by enzymes in the body, so it only lingers for a few minutes. Therefore, if it were to be used as a drug, patients would face the undesirable prospect of needing the necessary treatment. GLP– 1 injection every hour.

In 1990, John Eng, a researcher at the Veterans Affairs Medical Center in the Bronx, discovered that exendin-4, a hormone found in Gila monster venom, was similar to human venom. GLP-1. Importantly, exendin-4, which is released after the monster’s rare meals, is more resistant to enzymatic degradation than exendin-4. GLP-1, Stays in the body for hours. It took more than a decade for exenatide, a synthetic version of the lizard hormone developed by American pharmaceutical giant Eli Lilly and biotechnology company Amylin Pharmaceuticals, to be approved as a diabetes treatment in the United States. This breakthrough has inspired other companies to develop more effectively and over the long term. GLP-1 Drug therapy as a treatment option for diabetes beyond insulin injections.

Scientists also recognized that GLP-1 had another side effect. It slowed down the rate of “gastric emptying,” which causes food to stay in the stomach longer and suppresses appetite. However, its potential weight loss benefits were not initially seriously pursued. It was in 2021 that Danish company Novo Nordisk presented data from a clinical trial of weekly doses of its product to overweight or obese patients. GLP-1-based diabetes drug semaglutide was sold for 68 weeks under the name Ozempic at the time. The results were dramatic, with participants losing an average of 15% of their body weight.

fat profits

Drugs that imitate it are GLPThen -1 Hormone became a big hit. With nearly half of the world’s population expected to be obese or overweight by 2030, demand for these drugs is soaring, according to the World Obesity Federation. Data provider Bloomberg estimates that annual sales of these drugs will reach $80 billion by then. . The market is expected to grow by 26% annually over the next five years. In comparison, he said, the two largest areas, oncology drugs, at 16% per year and immunotherapy drugs, at 4% per year.

only 3 for now GLP-1 drugs are approved to treat obese or overweight individuals: liraglutide and semaglutide, developed by Novo. and tirzepatide (manufactured by Lilly). However, there is already a wave of competitors on the market (see Figure 1). Bloomberg tracks his nearly 100 new drugs in the development pipeline. Most new treatments aim to surpass semaglutide and tirzepatide by developing drugs that are easier to take, have fewer side effects, and produce more effective weight loss (see Figure 2).

Let’s start with convenience. Both semaglutide and tirzepatide are injections that must be taken weekly. If treatment is discontinued, most of the weight will be regained within a year. American biotech giant Amgen is developing an anti-obesity drug that relies on once-monthly dosing, with the hope that weight loss effects will continue even after treatment ends. AMG133 activates the following receptors: GLP-1 (GIP), a hormone secreted in the small intestine in response to food intake that stimulates the production of both insulin and glucagon. The company is currently conducting clinical trials to see if patients can gradually taper off and move to lower doses over time.

Switching from injections to tablets will greatly increase drug tolerance, even for people who hate needles. Novo is working on an oral version of semaglutide that would be as effective as the jab. However, tablets require 20 times more active ingredient than injections and must be taken daily. Short supply of semaglutide has forced Novo to postpone the launch of its oral formulation. Lily also takes daily medication to: GLP-1 receptor called orforglyprone in late-stage clinical trials.

Another drawback is GLP-1-based drugs, nausea and vomiting frequently accompany their use. Danish biotechnology company Zealand Pharma is developing a drug based on another hormone called amylin, which is produced in the pancreas along with insulin in response to food intake.But it’s different GLP-1 suppresses appetite, and amylin causes satiety, the feeling of being full after a meal.

In most people, a hormone called leptin is released from fat tissue and signals to the brain that the body is full, says Zealand’s Adam Stesberg. Obese people are less sensitive to this hormone. Clinical studies have shown that analogs of amylin can resensitize people to leptin and help them stop eating early. Feeling full, rather than reducing appetite, may also reduce nausea. Steesberg said early-stage trial results suggest the drug can achieve similar weight loss as before. GLP-1 I am using medication, but my nausea and vomiting have been alleviated.

In addition to the awkward injections and nausea, the bigger concern is that patients taking these drugs don’t just shed fat, they also lose lean muscle mass. Lean body mass is lost by approximately 40% of body weight in some patients, which is a serious concern in older patients. To combat this, companies are trying to: GLP-1 drug, a drug originally designed to treat muscle atrophy.

American pharmaceutical company Regeneron is testing a drug that blocks myostatin and activin, proteins that inhibit muscle growth in the body. When used in combination with semaglutide, it may improve the quality of weight loss by maintaining lean muscle. Similarly, California-based biotech company BioAge is testing a drug that activates apelin receptors that could be used in combination with Lilly’s tirzepatide. Apelin is a hormone secreted after exercise that acts on skeletal muscles, the heart, and the central nervous system to regulate metabolism. and promotes muscle regeneration. In obese mice, this combination resulted in greater weight loss compared to tirzepatide alone while preserving lean tissue.

Slimming pills aren’t just for weight loss. Because obesity is associated with more than 200 health problems, including stroke, kidney problems, and fatty liver. GLP-1 Drugs have been proven to be more than just obesity.

A recent clinical trial by Novo, which was conducted for five years and involved more than 17,500 participants, found that semaglutide reduced the risk of serious heart disease, including heart attacks, strokes, and death from heart disease, by 20%. It turns out that it does. Novo believes the heart benefits of this treatment are not due to weight loss alone, as reductions in cardiovascular disease risk are seen early, even before patients lose weight. Semaglutide was approved in March. we The Food and Drug Administration is aiming to reduce the risk of heart disease in people who are obese or overweight, and has approved a weight-loss drug for this purpose for the first time. Results from another clinical trial showed that semaglutide reduced the risk of kidney disease-related events by 24% in patients with type 2 diabetes.

Another weight loss drug, sulbodutide, being developed by German drug companies Boehringer Ingelheim and Zeeland, has shown promising results in treating a serious liver disease called metabolic dysfunction-related steatohepatitis (mash). This is caused by excess fat accumulation within the liver and can lead to liver cancer and liver failure. In a recent trial of 295 patients, 83% saw significant improvement in symptoms when treated with sulvodutide, compared to 18% in the placebo group.Sulbodutide targets the following receptors GLP-1 and glucagon. Waheed Jamal of Boehringer Ingelheim says there is evidence that glucagon breaks down more fat in the liver. GLP-1 and reduce fibrosis (the buildup of excess scar tissue within the liver).

Gut meets brain

Much of the focus has been on the actions of these drugs to improve metabolic health, but scientists are now revealing that these drugs also play a role in the brain and immune system. GLP-1 receptors in the brain.

Daniel Drucker, a diabetes researcher at Toronto’s Mount Sinai Hospital, found that mice suffering from widespread inflammation throughout the body GLP-1 The drug reduced symptoms, but only if the receptors in the brain were not blocked. When the receptors in the mouse brain are blocked or genetically deleted, the drug loses its anti-inflammatory properties. this is, GLP-1 Drugs suppress inflammation by acting on brain cells.

This suggests that these drugs could be useful in treating brain disorders characterized by inflammation, such as Alzheimer’s disease and Parkinson’s disease, both of which are characterized by brain inflammation. Since 2021, Novo has been conducting a clinical trial involving more than 1,800 patients to test whether semaglutide helps patients in the early stages of Alzheimer’s disease. This research is expected to be completed by 2026.

Dr. Drucker believes that it has anti-inflammatory properties such as: GLP-1 Drugs are the key to versatility. In addition to Alzheimer’s and Parkinson’s disease, chronic inflammation is a contributing factor to many complications in people with type 2 diabetes and obesity, he notes, affecting organs such as the kidneys, heart, blood vessels, and liver. If these drugs ultimately help treat these conditions, Dr. Drucker thinks their inflammation-reducing properties may explain some of their success.

The appetite-suppressing effects of these drugs have also led to increased interest in their ability to suppress cravings for other substances. Danish researchers investigated the effects. GLP-1 Drugs for people with alcohol use disorders. A study of 130 people found no differences between patients who took the drug (alongside treatment) and those who took a placebo. However, obese patients’ alcohol intake decreased. When the researchers showed patients pictures of alcoholic beverages and looked at their brain activity, the brain’s reward centers were activated in patients in the placebo group.For patients GLP-1 The drug reduced brain activity in areas associated with reward and addiction, indicating a direct effect on the brain. Some researchers are currently actively investigating whether this drug may affect the way people use other addictive substances, such as tobacco and marijuana.

All of these discoveries are still in their early stages. Developing new drugs is expensive and time consuming. The failure rate is very high. Success in the lab may not work in humans, and results in small groups may not be reproducible in large groups. But hopes for the new drug continue to grow, with the potential to treat dozens of diseases far beyond obesity and diabetes. ■