GLP-1s

Benjamin Mctavish
Apr 1
5 min read

What are GLP-1s?

GLP-1s are typically administered as injectables.

This involves injecting a liquid medication using a needle and syringe.

These GLP-1s are known by several names:

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

These medications are relatively recent developments. The U.S. Food and Drug Administration (FDA) approved the first GLP-1 agonist, exenatide, in 2005. Researchers continue to explore their potential applications and benefits.

GLP-1 agonists alone are not sufficient to treat Type 2 diabetes or obesity. Both conditions require additional treatment strategies, such as lifestyle and dietary modifications.

Comprehensive List of GLP-1 Agonists

The following GLP-1 agonists are available in the United States:

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

A related category, dual GLP-1/GIP receptor agonists, includes tirzepatide (Mounjaro®).

Mechanism of Action of GLP-1 Agonists

To comprehend the mechanism of GLP-1 agonists, it is essential to understand the function of the naturally occurring GLP-1 hormone.

GLP-1 is a hormone produced by the small intestine. It serves several functions, including:

Stimulating insulin release from the pancreas: Insulin is a crucial hormone that enables the body to utilize food for energy by reducing blood glucose levels. Insufficient insulin leads to increased blood sugar, resulting in diabetes.
Inhibiting glucagon secretion: Glucagon is a hormone that raises blood sugar levels when necessary. GLP-1 prevents excess glucose from entering the bloodstream.
Delaying gastric emptying: Slower digestion results in reduced glucose release into the bloodstream from ingested food.
Enhancing satiety: GLP-1 influences brain regions that regulate hunger and fullness.

GLP-1 agonist medications function by mimicking this hormone. An agonist in pharmacological terms is a synthetic substance that binds to a cell receptor, eliciting the same response as the natural hormone. Thus, GLP-1 medications attach to GLP receptors to induce the effects of the GLP-1 hormone. Higher doses of GLP-1 agonists amplify these effects.

For individuals with Type 2 diabetes, these medications assist in blood sugar management by stimulating increased insulin release from the pancreas. Additionally, the delayed digestion helps mitigate blood sugar spikes.

The satiety effect of GLP-1 agonists decreases food intake, appetite, and hunger, often leading to weight loss.

Indications for GLP-1 Agonist Use

Healthcare professionals prescribe GLP-1 agonists for managing Type 2 diabetes and obesity.

GLP-1 Agonists in Type 2 Diabetes Management

The FDA has approved GLP-1 agonists for managing Type 2 diabetes (T2D) due to their ability to lower blood sugar levels.

There are various diabetes medications, including oral options. One common oral medication is metformin, often the first choice for T2D treatment. However, a healthcare provider may recommend a GLP-1 agonist if:

Metformin is ineffective in managing T2D.
Metformin is contraindicated for the patient.
The patient’s A1C level exceeds the target.
The target A1C is not achieved within three months of treatment, accompanied by conditions such as atherosclerosis, heart failure, or chronic kidney disease.

Effective T2D management typically involves multiple strategies, including:

Lifestyle and dietary modifications.
Regular exercise.
Pharmacotherapy.

Working together, you and your healthcare provider will develop a personalized treatment plan. Providers often prescribe GLP-1 agonists alongside other medications to optimize blood glucose control.

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

Researchers are currently investigating the safety and efficacy of GLP-1 agonists for individuals with Type 1 diabetes (T1D). Initial studies suggest these medications may help reduce A1C levels and assist with weight loss in T1D patients.

The FDA has not approved GLP-1 agonists for T1D treatment. However, some healthcare providers may prescribe them off-label. Consult your provider to determine if this option is suitable for you.

GLP-1 agonists for obesity

The FDA has approved the use of semaglutide and high-dose liraglutide for obesity treatment due to their weight loss effects. Obesity is defined as having a body mass index (BMI) of 30 or higher.

Healthcare providers may also prescribe semaglutide or high-dose liraglutide to individuals who are overweight and have other health conditions, if weight loss could help manage these conditions. Overweight is characterized by a BMI of 25 to 29.9.

Obesity is a complex condition requiring multiple therapies for effective management, including:

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

If you are dealing with obesity or being overweight, consult your healthcare provider to determine if a GLP-1 agonist is appropriate for you.

Treatment Details

How often do you take GLP-1 agonists?

Your healthcare provider will advise on the timing and frequency of your medication (typically injections). Ensure to follow their guidance.

Generally, the injection frequencies 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 taken daily.

Risks / Benefits

What are the potential benefits of GLP-1 agonists?

In addition to lowering blood sugar and reducing weight, studies indicate GLP-1 agonists may offer other benefits, such as:

Lowering blood pressure.
Improving lipid disorders.
Improving fatty liver disease.
Reducing the 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 occur when starting the medication or increasing the dose.

Other side effects may include:

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

You may also experience temporary mild itchiness and/or redness at the injection site.

Severe but rare side effects can include:

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

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

GLP-1 agonists are generally safe, but there are some risks to consider, including:

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

GLP-1 agonists and allergic reactions

Some individuals may develop antibodies to GLP-1 agonists, especially with exenatide. This can affect the medication's effectiveness and cause allergic reactions at the injection site or potentially anaphylaxis, a severe allergic reaction.

If you experience persistent itchiness, redness, or other allergic reaction symptoms at injection sites, consult your healthcare provider.

If you exhibit symptoms of anaphylaxis, call 911 or proceed 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 are not safe for use during pregnancy. Animal studies have shown these medications can cause developmental abnormalities in the fetus.

If you are capable of becoming pregnant, it is essential to use effective and reliable birth control while taking a GLP-1 agonist. If you become pregnant while on the medication, contact your healthcare provider immediately.

GLP-1 agonists and hypoglycemia

There is a low risk of mild low blood sugar (hypoglycemia) episodes when taking a GLP-1 agonist. This risk can become significant if GLP-1s are taken with other blood sugar-lowering medications, such as sulfonylureas or insulin.

Hypoglycemia is defined as blood sugar levels below 70 mg/dL. Without appropriate treatment, severe hypoglycemia can be life-threatening. Symptoms of hypoglycemia include: