What Are GLP-1 Agonists? Uses for Diabetes and Weight Loss. 

Introduction:

GLP-1 agonists represent a category of drugs primarily utilized to regulate blood sugar (glucose) levels in individuals diagnosed with Type 2 diabetes. Additionally, certain GLP-1 agonists may assist in the treatment of obesity.

GLP-1 agonists are predominantly administered via injection, which involves delivering a liquid medication using a needle and syringe. The injections are performed in the fatty tissue located just beneath the skin (subcutaneous injection). Suitable areas for these injections include the abdomen, outer thighs, upper buttocks, and the rear of the arms.

Other names for this medication class include:

• Glucagon-like peptide-1 agonists.
• GLP-1 receptor agonists.
• Incretin mimetics.
• GLP-1 analogs.

These treatments are relatively novel. The U.S. Food and Drug Administration (FDA) approved the first GLP-1 agonist (exenatide) in 2005. Ongoing research is focused on uncovering their additional potential uses and benefits.

GLP-1 agonists on their own cannot effectively treat Type 2 diabetes or obesity. Both conditions require supplementary treatment strategies, such as changes in lifestyle and diet.

A.   GLP-1 agonist medications List

GLP-1 agonist medications currently available on the U.S. market include:

• Dulaglutide (Trulicity®).
• Exenatide (Byetta®).
• Exenatide extended-release (Bydureon®).
• Liraglutide (Victoza®).
• Lixisenatide (Adlyxin®).
• Semaglutide injection (Ozempic®).
• Semaglutide tablets (Rybelsus®).

There exists a comparable category of drugs known as dual GLP-1/GIP receptor agonists. At present, there is one such medication available in the market. This medication is referred to as tirzepatide (Mounjaro®).

 

B.   How do GLP-1 agonists work?

To understand how GLP-1 agonists work, it helps to understand how the naturally occurring GLP-1 hormone works.

GLP-1 is a hormone synthesized by your small intestine. It has various functions, such as:

• Inducing insulin secretion from the pancreas: Insulin is a vital hormone that allows your body to convert the food you consume into energy. It decreases the concentration of glucose (sugar) in your blood. Insufficient insulin can lead to increased blood sugar levels, which may result in diabetes.

• Suppressing glucagon release: Glucagon is a hormone that your body utilizes to elevate blood sugar levels when necessary. Thus, GLP-1 prevents additional glucose from entering your bloodstream.

• Slowing the process of stomach emptying: A slower digestive rate means that your body releases less glucose (sugar) from the food you consume into your bloodstream.

• Increasing the sensation of fullness after eating (satiety): GLP-1 impacts areas of your brain that regulate hunger and feelings of fullness.

GLP-1 agonist therapies work by simulating this hormone. In pharmacological terminology, an agonist is a created substance that binds to a cell receptor and produces the same effect as the naturally occurring substance. In other words, GLP-1 medications attach to GLP receptors to activate the effects (or roles) of the GLP-1 hormone. The increased dosage of the GLP-1 agonist results in more intense effects. For individuals with Type 2 diabetes, these medications help manage blood sugar levels by stimulating the pancreas to release more insulin. The slowed digestion also plays a role in reducing blood sugar spikes.

GLP1-agonists promote a feeling of fullness that lowers your food intake, appetite, and hunger levels. As a result, these combined effects typically lead to weight loss.

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C.   When would I need to take a GLP-1 agonist?

Healthcare providers prescribe GLP-1 agonists for two conditions: Type 2 diabetes and obesity.

GLP-1 agonists for Type 2 diabetes

• The FDA has authorized the use of GLP-1 agonists to assist in the management of Type 2 diabetes (T2D). This is because GLP-1 agonists contribute to lowering blood sugar levels.

There are numerous other forms of diabetes medications, such as oral medications that are taken by mouth. One specific oral medication, metformin, is commonly the first-line treatment for T2D. Nevertheless, your healthcare provider may recommend a GLP-1 agonist if:

• Metformin does not adequately manage T2D.

• It is unsafe for you to take metformin (you have a contraindication).

• Your A1C level is above your target.

• You have not met your target A1C within three months of treatment and you have other conditions, such as atherosclerosis, heart failure, or chronic kidney disease.

It is essential to remember that the most effective management of T2D involves a combination of therapies, such as:

• Lifestyle and diet modifications.
• Exercise.
• Medications.

Together, you and your healthcare provider will determine a treatment plan that works best for you. Providers often prescribe GLP-1 agonists with other medications to achieve the best blood glucose management.

Can I take a GLP-1 agonist if I have Type 1 diabetes?

                   i.            Currently, researchers are examining the safety and effectiveness of GLP-1 agonists for patients with Type 1 diabetes (T1D). Thus far, some research suggests that these drugs can aid in lowering A1C and facilitate weight loss among individuals with T1D.

                 ii.            The FDA has yet to approve GLP-1 agonists for T1D treatment. Nevertheless, certain healthcare providers may prescribe it off-label. It is advisable to discuss with your provider whether this option is suitable for you.

D.   GLP-1 agonists for obesity

The FDA currently authorizes the use of semaglutide and high-dose liraglutide for the treatment of obesity. This approval is based on the weight loss effects of these GLP-1 agonists. Obesity is defined as a chronic condition characterized by a body mass index (BMI) of 30 or greater.

Healthcare professionals may also recommend semaglutide or high-dose liraglutide for individuals who are overweight and have additional health issues, provided that weight loss could assist in managing these concurrent conditions. Overweight is classified as having a BMI ranging from 25 to 29.9.

Obesity is a multifaceted condition. Effective management typically necessitates a combination of therapies, such as:

·         Dietary changes.

• Exercise.
• Medications.
• Behavior modification programs.
• Bariatric (weight loss) surgery.

If you have obesity or are overweight, talk to your healthcare provider to see if a GLP-1 agonist is right for you.

E.   Treatment Details

How often do you take GLP-1 agonists?

Your healthcare provider will tell you when and how often to take your medication (usually injections). Be sure to follow their instructions.

But, in general, the frequencies of the injections are:

• Dulaglutide: Once a week.
• Exenatide: Twice a day.
• Exenatide extended-release: Once a week.
• Liraglutide: Once a day.
• Lixisenatide: Once a day.
• Semaglutide: Once a week.
• Tirzepatide: Once a week.

Semaglutide tablets are a daily medication.

F.    Risks / Benefits

What are the potential benefits of GLP-1 agonists?

Other than lowering blood sugar levels and reducing weight, studies show that GLP-1 agonists may have other potential benefits, like:

• Lowering blood pressure.
• Improving lipid disorders.
• Improving fatty liver disease.
• Reducing your risk of heart disease and kidney disease.
• Delaying the progression of diabetes-related nephropathy.

• What are the side effects of GLP-1 agonists?

The most common side effects of GLP-1 agonists include:

• Loss of appetite.
• Nausea.
• Vomiting.
• Diarrhea.

These side effects are more likely to happen when you start the medication or if you’re taking an increased dose.

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Other side effects can include:

• Dizziness.
• Mild tachycardia (increased heart rate).
• Infections.
• Headaches.
• Indigestion (upset stomach).

You may also have temporary mild itchiness and/or redness on your skin at the site of the injections.

Severe — but rare — side effects can include:

• Pancreatitis.
• Medullary thyroid cancer.
• Acute (sudden) kidney injury.
• Worsening diabetes-related retinopathy.

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What are the risks or complications of GLP-1 agonists?

GLP-1 agonists are generally safe. But there are a few risks to consider, including:

• Allergic reactions.
• Use during pregnancy.
• Low blood sugar (hypoglycemia).

• GLP-1 agonists and allergic reactions

Certain individuals develop antibodies against GLP-1 agonists, especially with exenatide. This may lead to complications regarding the medication's efficacy. Additionally, it can result in allergic reactions at the injection site and may even lead to anaphylaxis, a serious allergic response.

If you experience ongoing itchiness, redness, or any other signs of an allergic reaction at the injection sites, consult your healthcare provider.

If you have symptoms of anaphylaxis, call 911 or get to the nearest emergency room.

Symptoms of anaphylaxis include:

• Shortness of breath or wheezing.
• Hives.
• Difficulty swallowing.
• Red rash.
• Abdominal (belly) pain.
• Chest tightness.
• A feeling of doom or dread.

• GLP-1 agonists and pregnancy

GLP-1 agonists aren’t safe to take during pregnancy. Animal studies show that these medications cause developmental abnormalities in the fetus.

If you’re able to become pregnant, you should use effective and reliable birth control while taking a GLP-1 agonist. If you become pregnant while taking the medication, see your healthcare provider immediately.

G.  GLP-1 agonists and hypoglycemia

The likelihood of experiencing mild low blood sugar (hypoglycemia) episodes is minimal when using a GLP-1 agonist. However, this risk can escalate significantly if GLP-1s are combined with other medications that reduce blood sugar levels, such as sulfonylureas or insulin.

Hypoglycemia is defined as having blood sugar levels below 70 mg/dL. If not treated appropriately, severe hypoglycemia can pose a life-threatening risk. Symptoms of hypoglycemia include:

• Shaking or trembling.
• Sweating and chills.
• Dizziness or lightheadedness.
• Weakness.
• Faster heart rate.
• Intense hunger (hyperphagia).
• Difficulty thinking and concentrating.
• Pale skin (pallor).
• Nausea.

To treat hypoglycemia, you need to consume sugar or carbohydrates, like half a banana or half a cup of apple juice.

H.  When To Call the Doctor

• When should I call my healthcare provider?

You should have regular appointments with your healthcare provider when taking a GLP-1 agonist to assess how well it’s working.

Otherwise, talk to your provider in the following situations:

• If you develop bothersome side effects.
• If you don’t think it’s working to manage your condition.
• If you’re thinking of stopping the medication.
• If you become pregnant or are thinking of becoming pregnant.

 

 Note:

There is no single "best" method for managing Type 2 diabetes or obesity. Each individual is distinct, and consequently, every treatment plan is tailored to the person. However, GLP-1 agonists could be beneficial. Consult your healthcare provider to determine if a GLP-1 agonist is suitable for you. They are available to assist you.

I.      Obesity & GLP-1 Drug Market Trends

The market for GLP-1 drugs is experiencing rapid growth on a global level, with projections indicating the potential to generate hundreds of millions in revenue from 2025 to 2034. Market predictions point to strong progress driven by heightened investments, innovation, and increasing demand across multiple sectors.

The demand and utilization of GLP-1 drugs for managing type 2 diabetes and obesity are on the rise. Companies are joining forces to develop and bring their products to market. Additionally, various platforms incorporating AI technology are being created. Concurrently, numerous research and development initiatives are underway to discover new applications and to create next-generation GLP-1 drugs. Consequently, their adoption in different regions is growing. Therefore, all these advancements are fostering market expansion.