GLP-1 agonists have also shown promise in reducing the risk of major adverse cardiovascular events, such as stroke and heart attack. This adds to their potential benefits in managing obesity and its related health complications.

Clinical Trial of Semaglutide and Bimagrumab

One promising avenue of research involves combining existing GLP-1 receptor agonists with experimental drugs designed to preserve muscle mass. A clinical trial, known as the BELIEVE Phase 2b study, is currently underway to test the combination of semaglutide and bimagrumab. Bimagrumab is a first-in-class, fully humanized monoclonal antibody developed by Versanis Bio, a clinical-stage biopharmaceutical company recently acquired by Eli Lilly. It targets activin type II receptors, which play a role in regulating muscle growth and fat storage. This trial aims to assess the efficacy and safety of bimagrumab in preserving or increasing muscle mass while promoting weight loss with semaglutide in non-diabetic patients with overweight or obesity.

To be eligible for the BELIEVE study, participants must have a body mass index (BMI) greater than or equal to 30, or greater than or equal to 27 with one or more obesity-related comorbidities. Key exclusion criteria include a history of hypersensitivity to monoclonal antibody drugs, treatment with any medication for obesity within 30 days before screening, and a diagnosis of diabetes requiring current use of any antidiabetic drug.

Pre-clinical studies have shown that blocking activin type II receptors with bimagrumab leads to increased lean mass and decreased fat mass in mice. In a Phase 2 study, bimagrumab produced a 22% reduction in fat mass and a 4.5% increase in lean mass in patients with type 2 diabetes and obesity. Notably, no weight regain was observed after stopping bimagrumab treatment, unlike the rebound effect often seen with GLP-1 therapies. This suggests that bimagrumab may offer long-term benefits in maintaining weight loss even after treatment cessation.

The ongoing clinical trial will provide valuable insights into the potential of combining semaglutide and bimagrumab to achieve superior fat loss while preserving muscle mass. This combination therapy could offer a more comprehensive weight management approach, addressing fat loss and muscle preservation.

Semaglutide and Bimagrumab: Mechanisms of Action

Semaglutide and bimagrumab work through distinct mechanisms to achieve their therapeutic effects. Semaglutide, a GLP-1 receptor agonist, mimics the action of GLP-1, a natural gut hormone crucial in regulating blood sugar and appetite. GLP-1 agonists work by

• Triggering insulin release from the pancreas
• Blocking glucagon secretion
• Slowing stomach emptying
• Increasing feelings of fullness

Semaglutide helps lower blood sugar levels, reduce appetite, and promote weight loss by mimicking these effects.

Bimagrumab, on the other hand, is a human monoclonal antibody directed against type II activin receptors (ActRII). Upon administration, bimagrumab binds to ActRII, which prevents binding the natural ligands, myostatin and activin, to activin receptors and blocks ActRII-mediated signalling. This increases protein synthesis, decreases protein degradation, stimulates skeletal muscle cell growth, and increases muscle function and strength10. Overstimulation of the ActRII-mediated signalling pathway is associated with muscle loss and weakness.

Other Anti-Obesity Drugs in Development

The success of semaglutide and tirzepatide has fueled a surge in the development of new anti-obesity drugs. These drugs target various biological pathways and aim to improve upon the limitations of existing therapies. Targeting multiple pathways simultaneously could allow for lower doses that achieve the same weight loss with fewer side effects. Some of the key areas of development include:

GLP-1 and GIP Receptor Agonists

Tirzepatide is a dual GLP-1 and GIP receptor agonist that has shown superior weight loss results compared to semaglutide in a large head-to-head trial by Eli Lilly. Participants who took tirzepatide lost an average of 20% of their body weight, outpacing the 14% reduction achieved with semaglutide. Tirzepatide is already available under the brand names Mounjaro and Zepbound.

There are two main strategies for modulating GIP activity: activation and blocking. While both approaches can lead to weight loss, they have different potential benefits and drawbacks. As seen with tirzepatide, GIP activation can further enhance energy metabolism and promote weight loss. However, some concerns blocking GIP signalling could adversely affect bone health, as GIP also plays a role in bone metabolism.

Amylin Analogues

Amylin is a hormone co-secreted with insulin that regulates blood sugar and appetite. CagriSema, a combination therapy developed by Novo Nordisk that pairs a long-acting analogue of amylin (cagrilintide) with semaglutide, has shown promising results in clinical trials. Participants in a 68-week, phase 3 trial lost an average of nearly 23% of their body weight.

Glucagon and GLP-1 Receptor Co-agonists

Glucagon is a hormone that raises blood sugar levels, while GLP-1 lowers them. Combining these two hormones in a single drug could offer a balanced approach to weight loss by increasing energy expenditure while maintaining blood sugar control. Survodutide, a glucagon and GLP-1 receptor co-agonist developed by Boehringer Ingelheim, is currently in clinical trials.

Triple-Hormone Receptor Agonists

Retatrutide, a triple-hormone receptor agonist developed by Eli Lilly that targets GLP-1, GIP, and glucagon receptors, has shown impressive weight loss results in Phase 2 trials. This drug, dubbed “triple G,” delivered an average weight reduction of 24% after 48 weeks, setting a new benchmark for obesity treatments.

Alternative Delivery Methods for Anti-Obesity Drugs

Companies are also exploring alternative delivery methods to once-weekly injections, which can be challenging to incorporate into people’s routines and come with manufacturing challenges. Once-monthly injectables are in the works, but oral formulations of GLP-1 receptor agonists, such as orforglipron produced by Eli Lilly, could arrive first.

Another potential alternative is oral semaglutide. In a phase 3 study called OASIS 1, people taking oral semaglutide 50 mg once daily lost up to 15% of their initial body weight after about 15 months (68 weeks) of use. This is comparable to the weight loss benefits of Wegovy, the injectable version of semaglutide.

Potential Side Effects of Anti-Obesity Drugs

While anti-obesity drugs offer a promising approach to weight management, they can also cause side effects. Some of the common side effects of GLP-1 receptor agonists include nausea, vomiting, diarrhoea, and constipation. More serious side effects, such as pancreatitis and gallbladder problems, are rare but can occur.

Specific side effects associated with semaglutide include nausea, vomiting, diarrhoea, abdominal pain, constipation, heartburn, and burping. In rare cases, semaglutide can cause more serious side effects such as pancreatitis, kidney problems, and changes in vision.

Tirzepatide can cause similar side effects, including nausea, diarrhoea, decreased appetite, vomiting, constipation, and stomach pain. Serious side effects, such as pancreatitis, gallbladder problems, and low blood sugar, can also occur.

Another concern with GLP-1 and GIP drugs is the potential risk of pulmonary aspiration during anaesthesia. These drugs can cause delayed gastric emptying, which may increase the risk of residual gastric contents despite preoperative fasting. This can lead to aspiration, where food or liquid gets into the lungs during surgery.

The increased demand for GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists has led to temporary product shortages. This has resulted in the emergence of compounded formulations of these drugs, which produce entities that bypass regulatory measures. The American Diabetes Association recommends against using non-FDA-approved compounded GLP-1 and dual GIP/GLP-1 receptor agonist products due to concerns regarding their safety, quality, and effectiveness. The FDA has also issued an alert on dosing errors associated with compounded semaglutide injectable products, which have led to adverse events and hospitalisations in some cases.

It is important to note that the potential side effects of anti-obesity drugs vary depending on the specific medication and individual factors. Patients should discuss these medications’ possible risks and benefits with their healthcare provider to determine the most appropriate treatment option.

Alternative Treatments for Obesity: Bariatric Surgery

For some individuals, bariatric surgery may be an alternative treatment option for obesity. Bariatric surgery involves making changes to your digestive system to help you lose weight. It is typically considered for people with a BMI of 40 or higher or those with a BMI of 35 or higher who have obesity-related health problems.

There are several types of bariatric surgery, including

• Roux-en-Y gastric bypass: This procedure involves creating a small pouch at the top of the stomach and connecting it directly to the small intestine, bypassing most of the stomach and the first section of the small intestine
• Sleeve gastrectomy: This procedure involves removing about 80% of the stomach, leaving a long, tube-like pouch
• Biliopancreatic diversion with duodenal switch (BPD/DS): This is a two-part surgery that involves performing a sleeve gastrectomy and then connecting the end of the small intestine to the duodenum, bypassing most of the small intestine

Bariatric surgery can be very effective for long-term weight loss and can also improve or reverse obesity-related conditions such as diabetes, high cholesterol, and sleep apnoea. However, it is a major surgical procedure with potential risks and complications, such as bleeding, infection, and leaks in the gastrointestinal system. Patients should carefully consider the risks and benefits of bariatric surgery with their healthcare provider.

Emerging Applications of GLP-1 and GIP Drugs

While GLP-1 and GIP drugs are primarily known for their role in treating obesity and type 2 diabetes, research is exploring their potential applications in other disease areas. These include:

• Neurodegenerative diseases: Conditions such as Parkinson’s and Alzheimer’s disease involve protein misfolding and chronic inflammation. Studies have found that GLP-1 mimetics can cross the blood-brain barrier and have neuroprotective effects, including reducing oxidative stress and chronic inflammatory responses in the brain.
• Liver disease: GLP-1 and GIP receptor agonists have shown potential in improving liver health, particularly in individuals with nonalcoholic fatty liver disease (NAFLD).

These emerging applications highlight the versatility of GLP-1 and GIP drugs and their potential to address a wide range of health challenges beyond obesity and diabetes.

Conclusion

The field of anti-obesity drug development is rapidly evolving, with new therapies emerging that offer the potential for more effective and personalised weight management. While GLP-1 receptor agonists like semaglutide and tirzepatide have revolutionised the field, ongoing research is exploring new targets and combination therapies to address the limitations of existing medications. These advancements, such as the combination of semaglutide and bimagrumab, the development of triple-hormone receptor agonists like retratrutide, and the exploration of alternative delivery methods, hold promise for improving the lives of millions of people struggling with obesity and its related health complications.

However, it is crucial to acknowledge the potential side effects of these therapies, including gastrointestinal issues, pancreatitis, and the risk of pulmonary aspiration during anaesthesia. Patients should carefully consider the risks and benefits of these medications with their healthcare provider to determine the most appropriate treatment option.

Developing new anti-obesity drugs has significant implications for public health and the future of obesity management. These advancements offer hope for a more comprehensive and personalised approach to weight loss, potentially reducing the burden of obesity and its associated health problems.

The post The Evolving Landscape of Anti-Obesity Drugs appeared first on Medika Life.

What is the difference between open and laparoscopic surgery?

In open bariatric surgery, surgeons make a single, large cut in the abdomen. More often, surgeons now use laparoscopic surgery, in which they make several small cuts and insert thin surgical tools through the cuts. Surgeons also insert a small scope attached to a camera that projects images onto a video monitor. Laparoscopic surgery has fewer risks than open surgery and may cause less pain and scarring than open surgery. Laparoscopic surgery also may lead to a faster recovery.

Open surgery may be a better option for certain people. If you have a high level of obesity, have had stomach surgery before, or have other complex medical problems, you may need open surgery.

What are the surgical options?

In the United States, surgeons use three types of operations most often:

• laparoscopic adjustable gastric band
• gastric sleeve surgery, also called sleeve gastrectomy
• gastric bypass

Surgeons use a fourth operation, biliopancreatic diversion with duodenal switch, less often.

Laparoscopic Adjustable Gastric Band

In this type of surgery, the surgeon places a ring with an inner inflatable band around the top of your stomach to create a small pouch. This makes you feel full after eating a small amount of food. The band has a circular balloon inside that is filled with salt solution. The surgeon can adjust the size of the opening from the pouch to the rest of your stomach by injecting or removing the solution through a small device called a port placed under your skin.

After surgery, you will need several follow-up visits to adjust the size of the band opening. If the band causes problems or is not helping you lose enough weight, the surgeon may remove it.

The U.S. Food and Drug Administration (FDA) has approved use of the gastric band for people with a BMI of 30 or more who also have at least one health problem linked to obesity, such as heart disease or diabetes.

Gastric Sleeve

In gastric sleeve surgery, also called vertical sleeve gastrectomy, a surgeon removes most of your stomach, leaving only a banana-shaped section that is closed with staples. Like gastric band surgery, this surgery reduces the amount of food that can fit in your stomach, making you feel full sooner. Taking out part of your stomach may also affect gut hormones or other factors such as gut bacteria that may affect appetite and metabolism. This type of surgery cannot be reversed because some of the stomach is permanently removed.

Gastric Bypass

Gastric bypass surgery, also called Roux-en-Y gastric bypass, has two parts. First, the surgeon staples your stomach, creating a small pouch in the upper section. The staples make your stomach much smaller, so you eat less and feel full sooner.

Next, the surgeon cuts your small intestine and attaches the lower part of it directly to the small stomach pouch. Food then bypasses most of the stomach and the upper part of your small intestine so your body absorbs fewer calories. The surgeon connects the bypassed section farther down to the lower part of the small intestine. This bypassed section is still attached to the main part of your stomach, so digestive juices can move from your stomach and the first part of your small intestine into the lower part of your small intestine. The bypass also changes gut hormones, gut bacteria, and other factors that may affect appetite and metabolism. Gastric bypass is difficult to reverse, although a surgeon may do it if medically necessary.

Duodenal Switch

This surgery, also called biliopancreatic diversion with duodenal switch, is more complex than the others. The duodenal switch involves two separate surgeries. The first is similar to gastric sleeve surgery. The second surgery redirects food to bypass most of your small intestine. The surgeon also reattaches the bypassed section to the last part of the small intestine, allowing digestive juices to mix with food.

This type of surgery allows you to lose more weight than the other three. However, this surgery is also the most likely to cause surgery-related problems and a shortage of vitamins, minerals, and protein in your body. For these reasons, surgeons do not perform this surgery as often.

Most Common Weight-loss Surgeries

Gastric Band

What it is

Surgeon places an inflatable band around top part of stomach, creating a small pouch with an adjustable opening.

Pros

• Can be adjusted and reversed.
• Short hospital stay and low risk of surgery-related problems.
• No changes to intestines.
• Lowest chance of vitamin shortage.

Cons

• Less weight loss than other types of bariatric surgery.
• Frequent follow-up visits to adjust band; some people may not adapt to band.
• Possible future surgery to remove or replace a part or all of the band system.

Gastric Sleeve

What it is

Surgeon removes about 80 percent of stomach, creating a long, banana-shaped pouch.

Pros

• Greater weight loss than gastric band.
• No changes to intestines.
• No objects placed in body.
• Short hospital stay.

Cons

• Cannot be reversed.
• Chance of vitamin shortage.
• Higher chance of surgery-related problems than gastric band.
• Chance of acid reflux.

Gastric Bypass

What it is

Surgeon staples top part of stomach, creating a small pouch and attaching it to middle part of small intestine.

Pros

• Greater weight loss than gastric band.
• No objects placed in body.

Cons

• Difficult to reverse.
• Higher chance of vitamin shortage than gastric band or gastric sleeve.
• Higher chance of surgery-related problems than gastric band.
• May increase risk of alcohol use disorder.

What should I expect before surgery?

Before surgery, you will meet with several health care providers, such as a dietitian, a psychiatrist or psychologist, an internist, and a bariatric surgeon.

• The doctor will ask about your medical history, do a thorough physical exam, and order blood tests. If you are a smoker, he or she will likely ask you to stop smoking at least 6 weeks before your surgery.
• The surgeon will tell you more about the surgery, including how to prepare for it and what type of follow-up you will need.
• The dietitian will explain what and how much you will be able to eat and drink after surgery and help you to prepare for how your life will change after surgery.
• The psychiatrist or psychologist may do an assessment to see if bariatric surgery is an option for you.

These health care providers also will advise you to become more active and adopt a healthy eating plan before and after surgery. In some cases, losing weight and bringing your blood sugar levels closer to normal before surgery may lower your chances of having surgery-related problems.

Some bariatric surgery programs have groups you can attend before and after surgery that can help answer questions about the surgery and offer support.

What should I expect after surgery?

After surgery, you will need to rest and recover. Although the type of follow-up varies by type of surgery, you will need to take supplements that your doctor prescribes to make sure you are getting enough vitamins and minerals.

Walking and moving around the house may help you recover more quickly. Start slowly and follow your doctor’s advice about the type of physical activity you can do safely. As you feel more comfortable, add more physical activity.

After surgery, most people move from a liquid diet to a soft diet such as cottage cheese, yogurt, or soup, and then to solid foods over several weeks. Your doctor, nurse, or dietitian will tell you which foods and beverages you may have and which ones you should avoid. You will need to eat small meals and chew your food well.

How much weight can I expect to lose?

The amount of weight people lose after bariatric surgery depends on the individual and on the type of surgery he or she had. A study following people for 3 years after surgery found that those who had gastric band surgery lost an average of about 45 pounds. People who had gastric bypass lost an average of 90 pounds. Most people regained some weight over time, but weight regain was usually small compared to their initial weight loss.

Researchers know less about the long-term results of gastric sleeve surgery, but the amount of weight loss seems to be similar to or slightly less than gastric bypass.

Your weight loss could be different. Remember, reaching your goal depends not just on the surgery but also on sticking with healthy lifestyle habits throughout your life.

Weight-loss Devices

The FDA has approved several new weight-loss devices that do not permanently change your stomach or small intestine. These devices cause less weight loss than bariatric surgery, and some are only temporary. The devices may have risks, so talk with your doctor if you’re thinking about any of these options. Researchers haven’t studied any of them over a long period of time and don’t know the long-term risks and benefits.

• The electrical stimulation system uses a device implanted in your abdomen, by way of laparoscopic surgery, that blocks nerve activity between your stomach and brain. The device works on the vagus nerve, which helps signal the brain that the stomach feels full or empty.
• The gastric balloon system consists of one or two balloons placed in your stomach through a tube inserted through your mouth. Your doctor or nurse will give you a sedative before the procedure. Once the balloons are in your stomach, doctors inflate them with salt water so they take up space in your stomach and help you feel fuller. You will need to have the balloons removed after 6 months or a year.
• A new device uses a pump to drain part of the food in your stomach after a meal. The device includes a tube that goes from the inside of your stomach to a port on the outside of your abdomen. The port is a small valve that fits over the opening in your abdomen. About 20 to 30 minutes after eating, you attach tubing from the port to the pump and open the valve. The pump drains your stomach contents through a tube into the toilet, so that your body doesn’t absorb about 30 percent of calories you ate. You can have the device removed at any time.

What are the side effects of bariatric surgery?

Side effects may include

• bleeding
• infection
• leaking from the site where the sections of the stomach or small intestine, or both, are stapled or sewn together
• diarrhea
• blood clots in the legs that can move to the lungs and heart

Rarely, surgery-related problems can lead to death.

Other side effects may occur later. Your body may not absorb nutrients well, especially if you don’t take your prescribed vitamins and minerals. Not getting enough nutrients can cause health problems, such as anemia and osteoporosis. Gallstones can occur after rapid weight loss. Some doctors prescribe medicine for about 6 months after surgery to help prevent gallstones. Gastric bands can erode into the stomach wall and need to be removed.

Other problems that could occur later include strictures and hernias. Strictures—narrowing of the new stomach or connection between the stomach and small intestine—make it hard to eat solid food and can cause nausea, vomiting, and trouble swallowing. Doctors treat strictures with special instruments to expand the narrowing. Two kinds of hernias may occur after bariatric surgery—at the incision site or in the abdomen. Doctors repair hernias with surgery.

Some research suggests that bariatric surgery, especially gastric bypass, may change the way your body absorbs and breaks down alcohol, and may lead to more alcohol-related problems after surgery.

The post Understanding the types of Bariatric Surgery appeared first on Medika Life.