GLP-1

Benefits of GLP-1

GLP-1 (Glucagon-Like Peptide 1) plays a pivotal role in regulating blood glucose or blood sugar, promoting weight loss, enhancing cardiovascular health, protecting nerves, and improving gut health. Its multifaceted benefits make it crucial for metabolic and neurological functions.

• Regulates blood sugar
• Promotes weight loss
• Improves cardiovascular health
• Protects the nerves
• Improves gut health

Key Takeaways of GLP-1

• GLP-1 is an incretin hormone that enhances the secretion of insulin from the pancreas in response to food intake, thereby lowering blood sugar levels.
• GLP-1 can help reduce appetite, leading to a decrease in food intake and assisting in weight management.
• GLP-1 slows down the rate at which food moves from the stomach to the small intestine, allowing for better absorption of nutrients.
• Some GLP-1 receptor agonists have shown cardiovascular benefits by reducing the risk of major cardiovascular events in people with type 2 diabetes.
• GLP-1 promotes the growth and survival of pancreatic β-cells, which produce insulin.
• GLP-1 receptor agonists are used as medications for treating type 2 diabetes due to their ability to regulate blood sugar and assist with weight loss.

What is GLP-1?

GLP-1 (Glucagon-Like Peptide 1) is a naturally occurring hormone produced in the gut, specifically in the L-cells of the ileum and colon. It plays a pivotal role in regulating blood glucose levels and appetite control. When we eat, GLP-1 is released into the bloodstream and has several key functions: it stimulates the pancreas to release insulin, which helps lower blood glucose it inhibits the release of glucagon, a hormone that raises blood sugar; it acts on the brain to reduce appetite and increase feelings of fullness, contributing to food intake regulation; and it slows the emptying of the stomach, leading to more gradual nutrient absorption and stabilized blood glucose levels. GLP-1 has become a target for medications used to treat type 2 diabetes mellitus and obesity, as it can help improve blood sugar control and promote weight loss when its effects are mimicked or enhanced.

GLP 1 Mechanism of Action

GLP-1, or Glucagon-Like Peptide 1, regulates blood glucose and appetite through multiple mechanisms. When we eat, GLP-1 is released from the small intestine and stimulates the pancreas to secrete insulin, which in turn helps lower blood glucose levels. It also inhibits glucagon secretion, which prevents the liver from releasing excess glucose into the bloodstream. GLP-1 acts on the brain to reduce appetite and increase the sensation of fullness, helping control food intake. Additionally, it slows down the emptying of the stomach, leading to gradual nutrient absorption and stable blood glucose levels. Overall, GLP-1 plays a vital role in glucose homeostasis and body weight regulation.

Chemical Structure of GLP-1

GLP 1 for Weight Loss

GLP-1, or glucagon-like peptide-1, is an incretin hormone produced in the intestines in response to food intake. It has a variety of roles related to metabolism, but one of its most notable effects is its ability to promote feelings of satiety, which can help reduce food intake and thus support weight loss.

GLP-1 exerts its weight loss effects through the following mechanisms:

• Satiety and Reduced Food Intake: GLP-1, originating from pancreatic alpha cells, helps slow gastric emptying, which means it takes longer for the stomach to empty its contents into the small intestine. This helps prolong the feeling of fullness after eating, potentially leading to reduced food intake, especially beneficial for overweight patients.
• Appetite Suppression: GLP-1 has a central effect on the brain, specifically in areas associated with appetite regulation and weight reduction. By acting on these neural pathways, GLP-1 can reduce the desire to eat, reducing weight and preventing weight gain.
• Metabolic Benefits: In addition to its appetite-related effects, GLP-1 also regulates blood glucose, which might have indirect benefits for weight management. For example, stable blood glucose levels can reduce cravings and decrease the desire for sugary or carbohydrate-rich snacks.

It’s worth mentioning that while GLP-1 agonists can be effective tools for weight loss, they are best used as part of a comprehensive weight management plan that includes dietary changes, exercise, and other lifestyle modifications. As with all medications, GLP-1 agonists can have side effects, so individuals need to discuss the risks and benefits with their healthcare provider.

GLP 1 Agonist Peptides

A GLP-1 agonist (glucagon-like peptide-1 agonist), also known as GLP 1 RA (glucagon-like peptide-1 receptor agonist), is a class of drugs that mimic the action of the body’s native GLP-1 hormone. GLP-1 is an incretin hormone produced in the intestines in response to food intake, which plays a role in glucose homeostasis by stimulating insulin secretion, inhibiting glucagon release, slowing gastric emptying, and promoting feelings of satiety.

GLP 1 receptor agonists are used primarily in treating type 2 diabetes mellitus to help lower blood sugar levels. This is the reason why they are also called glucose-lowering medications. They have the additional benefits of promoting weight loss and having a favorable effect on cardiovascular risk factors (e.g. heart failure).

Some examples of GLP 1 receptor agonists or GLP 1 drugs include:

• Exenatide (Byetta, Bydureon)
• Liraglutide (Victoza, Saxenda)
• Dulaglutide (Trulicity)
• Semaglutide (Ozempic, Rybelsus)
• Albiglutide (Tanzeum)
• Lixisenatide (Adlyxin, Soliqua)
• Tirzepatide
• Retatrutide

It’s worth noting that while they offer many advantages, GLP 1 receptor agonists also come with potential side effects, and it’s essential for patients to discuss these with their healthcare provider.

What is a GLP 1 analogue?

A GLP-1 analogue is a medication that mimics the action of the naturally occurring hormone glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone that is produced by the intestines and plays a role in regulating blood sugar levels.

GLP-1 analogues are used to treat type 2 diabetes mellitus and obesity. They work by stimulating the pancreas to produce more insulin and slowing down food digestion. This helps to lower blood sugar levels and promote weight loss.

GLP-1 analogues are typically given as a once-weekly injection or once a month. They are generally well-tolerated and have few side effects. However, some people may experience mild side effects such as nausea, vomiting, diarrhea, and abdominal pain.

GLP-1 analogues are an effective treatment for type 2 diabetes and obesity. They can help to improve glycemic control (blood sugar control), promote weight loss, and reduce the risk of cardiovascular disease such as heart failure.

If you are considering taking a GLP-1 analogue, be sure to talk to your doctor about the risks and benefits.

Are GLP-1 Analogues and GLP-1 Receptor Agonists the Same?

GLP-1 analogues and GLP-1 receptor agonists are not exactly the same thing, but they are very similar.

GLP-1 analogues are synthetic versions of the naturally occurring hormone glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone that is produced by the intestines and plays a role in regulating blood sugar levels and appetite.

GLP-1 receptor agonists are medications that bind to and activate the GLP-1 receptor. This mimics the action of GLP-1 and has the same effects on blood sugar levels and appetite.

In other words, all GLP-1 receptor agonists are GLP-1 analogues, but not all GLP-1 analogues are GLP-1 receptor agonists. For example, some GLP-1 analogues are used for research purposes and are not intended to be used as medications.

What are GLP 1 supplements?

GLP-1 supplements are dietary supplements claimed to increase the production or release of the hormone glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone produced by the intestines and plays a role in regulating blood sugar levels and appetite.

GLP-1 supplements are typically made from fiber, herbs, and probiotics. However, limited scientific evidence supports the claims that these supplements can effectively increase GLP-1 levels or have any health benefits.

Some of the most common ingredients in GLP-1 supplements include:

• Fiber: Fiber can help slow down food digestion, which can lead to increased GLP-1 release.
• Herbs: Some herbs, such as berberine and ginger, have been shown to have some effects on GLP-1 levels in animal studies. However, more research is needed to confirm these effects in humans.
• Probiotics: Probiotics are live microorganisms that are similar to the beneficial bacteria that live in the gut. Some studies have shown that probiotics may help to increase GLP-1 levels.

If you are considering taking a GLP-1 supplement, talk to your doctor first. Your doctor can help you determine if a GLP-1 supplement is right for you and can monitor you for any potential side effects.

GLP 1 Weight Loss Non-Diabetic

Glucose-lowering medications such as GLP-1 (Glucagon-like peptide-1) receptor agonists are injectable medications used primarily to manage type 2 diabetes mellitus. They work by mimicking the action of the body’s own GLP-1 hormone, which increases insulin release, reduces glucagon secretion (another hormone that raises blood sugar), and slows stomach emptying. This combination of effects helps lower blood sugar levels in people with type 2 diabetes. However, a known side effect of these medications is significant weight loss.

The significant weight loss effect of GLP-1 receptor agonists has led to interest in their use for obesity management, even in individuals without diabetes. Here are some points to consider about the use of GLP-1 agonists for weight loss in non-diabetic individuals:

• FDA Approval: Some GLP-1 receptor agonists, like semaglutide (under the brand name Wegovy), have been approved by the U.S. Food and Drug Administration (FDA) specifically for weight management in adults with obesity or overweight with at least one weight-related medical condition. It has undergone rigorous clinical trials for this indication and has been found effective and safe for weight loss in the approved population.
• Mechanism: The exact mechanism by which GLP-1 receptor agonists induce weight loss is not fully understood but is thought to involve reducing appetite and food intake, possibly by acting on the central nervous system.
• Effectiveness: The degree of weight loss varies among individuals but can be significant. In randomized clinical trials, participants often lose a meaningful percentage of their baseline body weight after a year of treatment. This is often combined with other lifestyle interventions, like diet and exercise.
• Side Effects: GLP-1 receptor agonists can have side effects as with any medication. Common ones include nausea, vomiting, diarrhea, and constipation. Most side effects are mild and decrease over time, but it’s crucial to be aware of them and discuss any concerns with a healthcare provider.
• Limitations: While GLP-1 receptor agonists can be effective, they are not a magic bullet for weight loss. They work best with a comprehensive weight management program that includes dietary changes, increased physical activity, and behavioral therapy.
• Cost: These medications can be expensive, and insurance coverage for non-diabetic use varies. It’s essential to check with insurance providers and consider the out-of-pocket costs.
• Consultation: If someone is interested in using a GLP-1 receptor agonist for weight loss, they should consult a healthcare provider who can assess their overall health, the potential risks and benefits of the medication, and guide a comprehensive weight management strategy.

In conclusion, GLP-1 receptor agonists can be effective tools for weight loss, even in non-diabetic individuals, but they are just one piece of a comprehensive weight management approach. It’s always essential to consult with a healthcare provider before starting any new medication or weight loss strategy.

Are GLP 1 Drugs Over The Counter?

No, GLP-1 drugs are not over-the-counter. They are prescription medications used to treat type 2 diabetes mellitus and obesity. GLP-1 drugs work by mimicking the action of the naturally occurring hormone glucagon-like peptide-1 (GLP-1). GLP-1 is a hormone produced by the intestines and regulates blood sugar levels and appetite.

GLP-1 drugs are typically given as a once-weekly injection or once a month. They are generally well-tolerated and have few side effects. However, some people may experience mild side effects such as nausea, vomiting, diarrhea, and abdominal pain.

GLP-1 drugs are an effective treatment for type 2 diabetes and obesity. They can help lower blood sugar, promote weight loss, and reduce the risk of cardiovascular disease.

Is Oral GLP 1 Agonist Available?

There is currently only one oral GLP-1 agonist approved by the FDA: oral semaglutide (Rybelsus). This oral medication is approved for treating type 2 diabetes and helps lower blood sugar levels by improving insulin secretion from the pancreas.

However, several other oral GLP-1 agonists are in development, and some are in late-stage clinical trials. These medications are expected to be approved by the FDA in the next few years.

Here are some of the oral GLP-1 agonists in development:

• Oral tirzepatide
• Oral dulaglutide
• Oral liraglutide
• Oral efpeglenatide
• Oral danuglipron

These medications are still in the early stages of development, so it is not yet clear when they will be available to patients.

Oral GLP-1 agonists are a promising new class of medications for the treatment of type 2 diabetes and obesity. They offer a number of advantages over injectable GLP-1 agonists, such as convenience, affordability, and fewer side effects.

If you are interested in learning more about oral GLP-1 agonists, talk to your doctor. They can help you to determine if an oral medication like GLP-1 agonist is right for you.

GLP-1 vs. GIP

IMG

GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide) are two hormones that are produced in the small intestine in response to food intake. Despite their similarities, there are significant differences between the two. Both hormones help to regulate blood sugar levels and appetite, which in turn achieves blood sugar control and significant weight loss.

Both food intake and blood sugar levels stimulate GLP-1. When blood sugar levels are high, GLP-1 levels also increase. This helps to lower blood sugar levels via slowed gastric emptying, stimulating the release of more insulin, and inhibiting the release of glucagon from the pancreas. GLP-1 also has a role in appetite regulation. It can suppress appetite and lead to weight loss. On the other hand, GIP is stimulated by food intake, but its levels are not affected by blood sugar levels. GIP helps regulate blood sugar levels by stimulating insulin release from the pancreas. GIP also has a role in appetite regulation. It can suppress appetite and lead to weight loss.

GLP-1 Dosage

The dosage of GLP-1 (Glucagon-Like Peptide 1) receptor agonists can vary depending on the specific medication and individual patient needs. These medications are typically administered via subcutaneous injection, with options such as a once-daily or once-weekly injection. The dosing frequency can be once a day or, for many patients, a more convenient once-weekly injection. The specific dosage and frequency, whether it’s a once-daily or a once-weekly injection, will be determined by a healthcare provider based on factors such as the patient’s medical history, current health status, and the particular GLP-1 agonist being prescribed. Patients must follow their healthcare provider’s dosing instructions carefully, especially when transitioning to a once-weekly injection, and not adjust their dosage without medical guidance to ensure safe and effective management of conditions like type 2 diabetes or obesity.

In addition to assessing blood sugar levels, healthcare providers should also assess cardiovascular outcomes in patients taking GLP-1 receptor agonists. This is because GLP-1 receptor agonists have been shown to reduce the risk of cardiovascular events (e.g. cardiovascular death or nonfatal myocardial infarction) in people with type 2 diabetes.

The following are the administration frequency for popular GLP-1 receptor agonists:

• Dulaglutide: Once a week
• Albiglutide: Once a week
• Liraglutide: Once a day
• Semaglutide: Once a week (subcutaneous), Once a day (oral)
• Exenatide BID: Twice daily
• Exenatide QW: Weekly
• Lixisenatide: Once a day
• Tirzepatide: Once a week
• Retatrutide: Once a week

Indications of GLP-1 Receptor Agonists

GLP-1 receptor agonists are a class of diabetes drugs that have expanded their indications over the years, owing to their efficacy and safety profile. Here’s a comprehensive list of indications for GLP-1 receptor agonists:

• Type 2 Diabetes Mellitus (T2DM): GLP-1 receptor agonists are primarily diabetes drugs used for the management of T2DM. They help improve glycemic control by stimulating insulin secretion and suppressing glucagon secretion in a glucose-dependent manner. The American Diabetes Association (ADA) currently advises individuals with type 2 diabetes on insulin to consider adding a GLP-1 receptor agonist (like Rybelsus, Ozempic, Bydureon, Trulicity, Victoza, and others) for extra glucose control, rather than just increasing the insulin dose.
• Patients with a Personal or Family History of Cardiovascular Disease: One of the remarkable benefits of GLP-1 receptor agonists is their potential to reduce the risk of major adverse cardiovascular events (e.g. heart failure or nonfatal myocardial infarction), especially in those with a personal or family history of such events. The latest guidelines from the American Heart Association/American Diabetes Association (AHA/ADA) on preventing cardiovascular disease (CVD) in adults with type 2 diabetes emphasize the importance of weight management. They recommend that healthcare professionals consider prescribing antihyperglycemic medications (diabetes drugs) that aid in weight loss, such as GLP-1 receptor agonists, due to their beneficial cardiovascular effects.
• Concomitant Use with Basal Insulin: Some patients may require combination therapy. GLP-1 receptor agonists can be effectively combined with basal insulin to achieve better glycemic control. The use of this combination may lessen the risk of hypoglycemia compared to using basal insulin alone.
• Weight Management: Beyond their role as diabetes drugs, GLP-1 receptor agonists have shown efficacy in weight management. Their appetite-suppressing effects can aid in a significant reduction in body weight in overweight or obese individuals.

GLP-1 Receptor Agonist Peptides vs GLP Receptor Agonist Non-Peptides

GLP-1 (Glucagon-like peptide-1) receptor agonists are a class of medications primarily used to treat type 2 diabetes mellitus. They function by mimicking the actions of the endogenous incretin hormone GLP-1, which increases insulin release and decreases glucagon release in a glucose-dependent manner, thus aiding in blood glucose control.

GLP-1 receptor agonists can be classified into two broad categories based on their chemical structure: peptide-based and non-peptide-based (small molecule) agonists.

1. GLP-1 Receptor Agonist Peptides:

These are analogs of the native GLP-1 molecule or are peptides that have similar action on the GLP-1 receptor. They are usually injected subcutaneously.

Examples:

• Semaglutide (Ozempic, Wegovy, Rybelsus): Another human GLP-1 analog with modifications to extend its duration of action.
• Tirzepatide (Mounjaro): This peptide is the first dual-action GLP-1 agonist that works on both the GLP-1 receptor and the GIP receptor. It has been shown to be the most effect of all of the GLP-1 currently available on the market.
• Exenatide (Byetta, Bydureon): Originally derived from the saliva of the Gila monster lizard.
• Liraglutide (Victoza, Saxenda): A human GLP-1 analog with a fatty acid side chain, allowing it to bind to plasma proteins and have a longer half-life.
• Dulaglutide (Trulicity): A fusion protein that combines GLP-1 with an IgG4 fragment to extend its half-life.

Pros:

• Extensive clinical data and experience
• Demonstrated efficacy in blood sugar control and often leads to weight loss
• Cardiovascular benefits have been demonstrated for some members of this class

Cons:

• Needs to be injected (except for oral semaglutide, Rybelsus)
• Potential for gastrointestinal side effects, like nausea or vomiting
• Rare risk of pancreatitis

2. GLP-1 Receptor Agonist Non-Peptides (Small Molecule Agonists):

These are smaller, non-peptide molecules that activate the GLP-1 receptor. Their development is challenging due to the complexity of mimicking the actions of a large peptide with a small molecule. As of my last update in January 2022, there weren’t any non-peptide GLP-1 receptor agonists approved for clinical use, but research in this area is ongoing.

Pros (theoretical, based on potential advantages):

• Could potentially be taken orally (if developed as oral agents)
• Might be less immunogenic than peptide-based agonists

Cons (theoretical):

• Less clinical data and experience compared to peptide agonists
• Unknown side effect profile

In summary, while peptide-based GLP-1 receptor agonists have established their place in the treatment of type 2 diabetes, the development and potential approval of non-peptide agonists might offer additional options for treatment with different routes of administration and pharmacokinetic profiles. As always, the selection of the right drug should be based on individual patient needs, potential benefits, and risks.

Contraindications of GLP-1 receptor agonists

GLP-1 receptor agonists are not recommended for patients with the following:

• Moderate renal impairment to severe renal impairment (kidney disease), characterized by a decreased estimated glomerular filtration rate (eGFR): The administration of GLP-1 receptor agonists in patients with this condition can increase the risk of kidney stones, pancreatitis, hypoglycemia, and adverse cardiovascular events. Therefore, these medications are not recommended for patients with kidney disease.
• Acute kidney injury: In cases of severe renal impairment (kidney disease) or those with a history of acute kidney injury, the use of GLP-1 receptor agonists warrants caution. While these diabetes drugs can offer benefits for chronic kidney disease, it’s essential to evaluate the risks and benefits in these scenarios.
• Personal or family history of medullary thyroid cancer: GLP-1 receptor agonists should not be given in patients with a personal or family history of medullary thyroid cancer (MTC) because these diabetes drugs have been associated with an increased risk of this cancer.
• Multiple endocrine neoplasia syndrome type 2 (MEN2): GLP-1 receptor agonists are not recommended for use in patients with multiple endocrine neoplasia syndrome type 2 (MEN2) because they have been shown to increase the risk of medullary thyroid cancer (MTC) in these patients. In preclinical studies involving rodents, some GLP-1 receptor agonists were found to induce thyroid C cell tumors, particularly medullary thyroid carcinoma (MTC), in rodent thyroid C cells. This finding led to concerns about the potential risk of MTC with these medications in humans.
• Hypersensitivity reactions to GLP-1 receptor agonists: The administration of GLP-1 receptor agonists in patients with hypersensitivity reactions to this medication or any of its components can increase the risk of allergic reactions.

GLP 1 Side Effects

GLP-1 receptor agonist side effects are very uncommon. There have been some side effects associated with its use wherein the patient had one of the issues listed below at some point while being on GLP-1 receptor agonists. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of GLP-1 receptor agonists. Despite this, it was listed as a side effect associated with GLP-1 receptor agonist therapy even though these associated side effects are very uncommon.

• Abdominal discomfort
• Allergic reactions
• Diarrhea
• Hypoglycemia (low blood sugar)
• Injection site reactions (redness, pain, or swelling)
• Nausea
• Pancreatitis (inflammation of the pancreas)
• Vomiting

It’s essential for individuals using GLP-1 receptor agonists to discuss potential side effects with their healthcare providers and monitor their response to the medication closely, including assessing cardiovascular outcomes. When considering these drugs, it’s also essential to take into account their cardiovascular safety.

Oral Non-peptide Glucagon-like Peptide-1 Receptor Agonist

Traditional peptide-based medications like incretin therapies face challenges when taken orally due to poor absorption in the body. Presently, available incretin therapies are primarily administered via injections or in the form of a pill known as semaglutide. However, oral absorption of these therapies is limited, with only a small fraction (0.4% to 1.0%) being effectively absorbed when taken on an empty stomach. Fortunately, researchers have identified an alternative approach that does not rely on peptides, leading to enhanced oral efficacy in incretin therapies. One such breakthrough is the non-peptide medication known as orforglipron, which demonstrates significantly improved oral absorption rates (20% to 40%) compared to semaglutide. Although oral non-peptide glucagon-like peptide-1 receptor agonist is not a peptide, it is included in this section because it works as an agonist to a peptide receptor (glucagon-like-peptide-1 receptor).