Glucagon-like peptide-1 (GLP-1) is a vital hormone produced by the intestine in response to food intake. Its main role is to regulate blood sugar levels, but it also helps to curb appetite, delay gastric emptying, and reduce post-meal blood sugar spikes.
GLP-1 agonists are medications that have revolutionized diabetes care, offering new hope for those seeking not only better blood sugar control but also weight loss and improved health.
What are GLP-1 Agonists?
Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) are a class of medications that have become increasingly prescribed for the management of type 2 diabetes. These drugs are designed to mimic the action of the natural hormone GLP-1, produced by the intestine in response to food intake. GLP-1 has a crucial role in regulating blood sugar levels and controlling appetite, making it an effective target for the treatment of type 2 diabetes.1,2
Types of GLP-1 Agonists
There are several types of GLP-1 agonists available, each with its own characteristics. GLP-1 drugs are known as GLP-1 agonists, GLP-1 receptor agonists, incretin mimetics, or GLP-1 analogs. The primary GLP-1 agonists on the market include:3
- Exenatide (Byetta, Bydureon)
Exenatide is typically administered by injection. Byetta is usually given twice daily before meals, while Bydureon is a long-acting form taken once a week.
- Liraglutide (Victoza)
Liraglutide is an injectable GLP-1 agonist that is usually taken once a day. It is known for its effectiveness in both blood sugar control and weight management.
- Dulaglutide (Trulicity)
Dulaglutide is a once-weekly injectable medication. It provides a convenient dosing schedule for individuals with type 2 diabetes.
- Semaglutide (Ozempic)
Semaglutide is another once-weekly injectable GLP-1 agonist. It has gained attention for its potent glucose-lowering and weight-loss effects.
- Lixisenatide (Adlyxin)
Lixisenatide is administered by injection and is usually taken once daily. It can be a suitable choice for those who prefer a daily dosing regimen.
How Do GLP-1 Agonists Work?
GLP-1 agonists, also known as glucagon-like peptide-1 receptor agonists, are a class of medications that play a crucial role in the management of type 2 diabetes mellitus. Here’s how they work:
Mechanism of Action
GLP-1 agonists mimic the action of the natural hormone GLP-1, produced by the intestine in response to food intake.
GLP-1 agonists promote insulin secretion in the pancreas. This insulin surge helps lower blood sugar levels after meals, which is important for people with type 2 diabetes who often experience post-meal glucose spikes.1,2
These medications also inhibit glucagon secretion, another hormone produced by the pancreas. Glucagon typically raises blood sugar levels, so by preventing its release, GLP-1 agonists contribute to blood sugar control.1,2
According to the American Diabetes Association (ADA), these drugs help lower HbA1c levels, a marker of long-term glucose management.4
GLP-1 agonists slow down digestion by delaying the emptying of the stomach. Delayed gastric emptying helps keep blood sugar levels steady by slowing the absorption of glucose from food, and it contributes to increased feelings of satiety and reduced appetite, potentially promoting weight management and weight loss.
One of the notable effects of GLP-1 agonists is their impact on body weight. These drugs can lead to weight loss in some individuals, partly due to reduced appetite and caloric intake.
Apart from their primary actions on blood sugar control and appetite, GLP-1 agonists have been associated with several other beneficial effects. Some GLP-1 agonists have demonstrated cardiovascular benefits, including improved blood pressure control and reduced risk of heart-related events in individuals with diabetes.
Research suggests that these medications might also have a protective effect on the kidneys in people living with diabetes.
GLP-1 Agonists Uses
GLP-1 agonists have several medicinal uses, primarily in managing metabolic and endocrine disorders. Let's explore the main uses of these drugs:
- For Type 2 Diabetes
One of the most common and well-established uses of GLP-1 agonists is treating type 2 diabetes. These medications are highly effective in helping individuals with type 2 diabetes manage their blood glucose levels and A1C. Depending on medical history and personalized factors, some healthcare providers will prescribe metformin before a GLP-1 receptor agonist.
- For Type 1 Diabetes
Glucagon-like peptide-1 (GLP-1) agonists are not U.S. FDA-approved for patients with type 1 diabetes, but some clinicians prescribe these drugs off-label for such patients.5
- Weight Management
Many individuals with type 2 diabetes struggle with weight gain. GLP-1 agonists have the added benefit of promoting weight loss in some cases, making them a favorable choice for those looking to shed excess pounds.6
It's important to note that the use of GLP-1 agonists in type 1 diabetes and obesity management is an evolving area of research and may not be appropriate for all individuals. The decision to use these medications should be made in consultation with a healthcare provider.
Benefits of GLP-1 Agonists
These medications offer a range of benefits for individuals with diabetes and those seeking help with weight management. Some of the key advantages include:
- Improved glycemic control
- Weight loss
- Appetite suppression
- Heart disease prevention
- A1c reduction
- Potential prevention of kidney disease in people with diabetes
- Blood pressure control
- Reduced risk of hypoglycemia
- Metabolic improvements including improved blood lipids (cholesterol, HDL, LDL, apolipoprotein b, and triglycerides)
Benefits may vary among different types of GLP-1 agonists, and individual responses can also vary. The choice of medication should be made in consultation with a healthcare provider to tailor the treatment to the individual's needs and goals.
GLP-1 Agonists Side Effects
While GLP-1 agonists offer several benefits in the management of diabetes and obesity, they may also be associated with certain side effects. It's important to be aware of both mild and severe side effects when considering these medications.7
Mild Side Effects
- Upset stomach
- Loss of appetite
- Injection site reactions (redness, pain, or swelling)
Severe Side Effects (Less Common)
- Pancreatitis (inflammation of the pancreas)
- Hypoglycemia (low blood sugar), especially when used in combination with other diabetes medications
- Thyroid tumors or thyroid cancer (rare but reported with some GLP-1 agonists)
- Allergic reactions, such as itching, rash, or swelling of the face, lips, or tongue (anaphylaxis)
- Acute kidney injury (rare, but has been reported)
The likelihood of experiencing severe side effects is relatively low, and many individuals tolerate GLP-1 agonists well. However, any unusual or severe symptoms should be promptly reported to a healthcare provider.
Before starting or changing medication, it's a good idea to have a thorough discussion with a healthcare professional to weigh the potential benefits against the possible risks and side effects. Individual responses to these medications can vary, and the choice of GLP-1 agonist should be based on a careful assessment of the patient's specific medical history and needs.
GLP-1 Agonists Risks and Complications
While GLP-1 agonists can be beneficial for many individuals, these medications may not be appropriate for some due to potential risks and complications. Several factors must be considered before starting the use of a GLP-1 agonist.
Individuals with known allergies to GLP-1 agonists or any of their components should not take these medications. Allergic reactions, though rare, can be severe and even life-threatening.
The safety of GLP-1 agonists during pregnancy has not been extensively studied. If you are pregnant, planning to become pregnant, or breastfeeding, it's important to discuss the risks and benefits of these medications with your healthcare provider. In many cases, alternative treatment options may be considered during pregnancy.
While GLP-1 agonists are less likely to cause hypoglycemia when used as a monotherapy, there is still a risk, especially when combined with other diabetes medications like insulin or sulfonylureas. Individuals at high risk for severe hypoglycemia may need to be cautious or explore alternative treatment options.
Other Possible Risks and Interactions
There have been reports of pancreatitis (inflammation of the pancreas) associated with GLP-1 agonists. Individuals with a history of pancreatitis or gallbladder disease may be at increased risk and should discuss alternative treatments with their healthcare provider.
Some GLP-1 agonists have been associated with an increased risk of thyroid tumors. Those with a history of thyroid disease or a family history of medullary thyroid carcinoma should exercise caution and discuss the potential risks with their healthcare provider.
GLP-1 agonists can sometimes cause gastrointestinal side effects, such as nausea, vomiting, and diarrhea. If these symptoms are severe or persistent, it may be necessary to change medication.
GLP-1 agonists may interact with other medications you are taking. Inform your healthcare provider of all the medications and supplements you are currently using to avoid potential interactions.
When to See a Doctor
Using GLP-1 agonists can be a valuable part of managing type 2 diabetes or obesity, but it's important to monitor for side effects or noticeable changes in your health. You should contact your healthcare provider in the following scenarios:
- Allergic Reactions: If you experience signs of an allergic reaction, such as itching, rash, swelling of the face, lips, or tongue, or have difficulty breathing, seek immediate medical attention. Allergic reactions to GLP-1 agonists, though rare, can be severe.
- Uncontrolled Blood Sugar: If your blood sugar levels are consistently elevated and not responding to the medication as expected, contact your healthcare provider. Adjustments to your treatment plan may be necessary.
- Persistent Gastrointestinal Symptoms: While some gastrointestinal side effects are common with GLP-1 agonists, if you experience severe or persistent symptoms like nausea, vomiting, or diarrhea, it's important to consult your healthcare provider. They can assess whether your treatment needs adjustment.
- Severe Hypoglycemia: If you experience episodes of severe hypoglycemia (very low blood sugar) while taking GLP-1 agonists, it's important to seek medical attention and discuss potential changes to your medication regimen.
- Pancreatitis Symptoms: Symptoms of pancreatitis, such as severe abdominal pain that may radiate to the back, nausea, and vomiting, should not be ignored. Contact your healthcare provider immediately if you experience these symptoms.
- Thyroid-Related Symptoms: Unusual thyroid-related symptoms, such as neck lumps, difficulty swallowing, or voice changes, should prompt you to seek medical evaluation. These can be associated with certain GLP-1 agonists.
- Pregnancy or Planning to Become Pregnant: If you are pregnant, planning to become pregnant, or breastfeeding, consult your healthcare provider. The safety of GLP-1 agonists during pregnancy is not well established, and alternative treatment options may need to be considered.
- Any Unusual or Severe Symptoms: If you experience any unusual or severe symptoms that you suspect may be related to your use of GLP-1 agonists, do not hesitate to reach out to your healthcare provider for evaluation and guidance.
You should have regular follow-up appointments with your healthcare provider to monitor your response to GLP-1 agonists and make necessary adjustments to your treatment plan. Open communication with your healthcare team will ensure that you receive the best care and achieve the maximum benefits from your medication.
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Topics discussed in this article:
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- Aaron King, Eden M. Miller; Glucagon-Like Peptide 1 Receptor Agonists Have the Potential to Revolutionize the Attainment of Target A1C Levels in Type 2 Diabetes—So Why Is Their Uptake So Low?. Clin Diabetes 1 April 2023; 41 (2): 226–238. https://doi.org/10.2337/cd22-0027
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- Jensterle, M., Rizzo, M., Haluzík, M., & Janež, A. (2022). Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. Advances in therapy, 39(6), 2452–2467. https://doi.org/10.1007/s12325-022-02153-x
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