GLP-1 Agonists: How They Work, Benefits & Side Effects

What Are GLP-1 Agonists?

GLP-1 agonists, also known as glucagon-like peptide-1 receptor agonists, are a class of medications primarily used to treat type 2 diabetes and obesity. They mimic the action of the natural GLP-1 hormone, which is released in the intestine after eating. GLP-1 helps regulate blood sugar by stimulating insulin secretion and reducing glucagon release. These medications also slow stomach emptying, which helps control appetite and enhances the feeling of fullness after meals. In recent years, some GLP-1 agonist drugs have also been approved for chronic weight management in people without diabetes.

How Do GLP-1 Agonists Work?

GLP-1 agonists help regulate blood sugar and appetite by targeting key pathways involved in digestion, insulin signalling, and brain signalling.

1. Mimicking the GLP-1 hormone: GLP-1 agonists activate GLP-1 receptors in the pancreas and brain, imitating the effects of the body's natural GLP-
2. Stimulating insulin secretion: They increase insulin production in response to high blood sugar, but only when glucose levels are elevated. This reduces the risk of hypoglycaemia (low blood sugar).
3. Suppressing glucagon release: They inhibit the secretion of glucagon, a hormone that raises blood sugar, from the pancreas's alpha cells.
4. Slowing gastric emptying: They delay the rate at which food moves through the stomach, helping to moderate post-meal blood sugar spikes and promoting feelings of fullness.
5. Reducing appetite: By acting on the brain's appetite centres, they decrease hunger and food cravings, supporting weight loss efforts.
6. Promoting satiety: They enhance the feeling of satisfaction after eating, helping to control calorie intake.

Benefits of GLP-1 Agonists

By targeting multiple systems involved in metabolism and cardiovascular health, GLP-1 agonists deliver benefits such as:

• They effectively lower blood sugar levels, particularly after meals.
• Support weight loss by reducing appetite and increasing feelings of fullness.
• Lower the risk of cardiovascular events in people with type 2 diabetes.
• Reduce blood pressure and cholesterol levels in some patients.
• Preserve pancreatic β-cell function, potentially slowing diabetes progression.
• May decrease all-cause mortality in people with type 2 diabetes.

FDA-Approved GLP-1 Agonist Medications

The National Institutes of Health provides a list of several GLP-1 agonist medications that are available, each with unique dosing and administration options:

• Exenatide
• Liraglutide
• Dulaglutide
• Semaglutide
• Lixisenatide
• Tirzepatide, a dual GIP/GLP-1 receptor agonist, is often grouped with GLP-1 drugs because of its overlapping mechanism of action..

Tests to Monitor Health While on GLP-1 Therapy for Type 2 Diabetes

If you're using GLP-1 agonists to manage type 2 diabetes, your doctor will likely recommend regular blood tests to monitor your progress and adjust your treatment plan as needed. These tests may include:

• Glycated Haemoglobin (HbA1c)
• Glucose Fasting Test
• Renal/Kidney Function Tests
• Liver Function Tests
• Thyroid Function Tests
• Lipid Profile
• Complete Blood Count (CBC)
• Diabetes Profile
• Postprandial or Fasting Blood Sugar

Uses of GLP-1 Agonists

GLP-1 agonists have gained widespread attention for their diverse therapeutic benefits across multiple medical conditions, such as:

• Type 2 Diabetes Management: GLP-1 agonists are primarily prescribed to improve blood sugar control in adults with type 2 diabetes, often when other medications have not been effective or are insufficient on their own.
• Weight Loss/Obesity Treatment: Certain GLP-1 agonists, such as semaglutide and liraglutide, are approved for chronic weight management in adults with obesity or overweight, especially when combined with diet and exercise.
• Cardiovascular Risk Reduction: Some agents in this class, like liraglutide and semaglutide, are approved to reduce the risk of major cardiovascular events in people with type 2 diabetes and established heart disease.
• Adjunct to Other Therapies: GLP-1 agonists may be combined with other glucose-lowering medicines, including metformin, SGLT2 inhibitors, or insulin, to achieve better glycaemic control.

Side Effects of GLP-1 Agonists

While generally well tolerated, GLP-1 agonists can cause gastrointestinal and other side effects, especially when starting treatment or increasing the dose. These include:

• Nausea
• Vomiting
• Diarrhoea
• Constipation
• Abdominal pain
• Loss of appetite
• Headache
• Injection site reactions (for injectable forms)

Less common but more serious side effects include a possible risk of pancreatitis (inflammation of the pancreas). In rare cases, these medications may also lead to gallbladder disease, kidney issues, or allergic reactions. If you experience severe or persistent symptoms, consult your doctor.

Who Should Avoid GLP-1 Agonists?

While GLP-1 agonists can be highly beneficial for many people with type 2 diabetes and obesity, they may not be suitable for everyone. You should avoid GLP-1 agonist drugs if you:

• Have a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2).
• Have a history of pancreatitis.
• Have a severe gastrointestinal disease, such as gastroparesis.
• If you are pregnant or breastfeeding.
• Have type 1 diabetes or diabetic ketoacidosis (GLP-1 agonists should not replace insulin in these cases).

How to Use GLP-1 Agonists Safely

Careful monitoring and following recommended guidelines are key to safely minimising GLP-1 agonists' potential complications. Follow these tips to use the medication safely:

1. Follow your doctor's prescription and dosage instructions carefully.
2. Start with a low dose and increase gradually to minimise gastrointestinal side effects.
3. Inject or take the oral medication at the same time each day as directed (if prescribed as a daily therapy).
4. Monitor blood sugar regularly, especially if taking other diabetes medications.
5. Report any severe abdominal pain, persistent nausea, or vomiting immediately (potential signs of pancreatitis).
6. Discuss all other medications and supplements with your doctor to avoid interactions.
7. Attend regular follow-up appointments to monitor side effects and ensure treatment effectiveness.
8. Store injectable medications as directed.

Comparison: GLP-1 Agonists vs. Other Diabetes Medications

Lifestyle Tips While on GLP-1 Agonists

In addition to taking your medication as prescribed, adopting healthy lifestyle habits can help you manage potential GLP-1 agonist side effects and optimise your treatment results. Some tips to maximise your treatment include:

• Eat smaller, more frequent meals to reduce gastrointestinal side effects.
• Stay hydrated, especially if experiencing vomiting or diarrhoea.
• Avoid high-fat, greasy foods that might worsen nausea.
• Monitor your blood sugar regularly as advised by your doctor.
• Engage in regular physical activity to support weight loss and improve overall health.
• Report any unusual abdominal pain to your doctor, as this could be a sign of a rare but serious side effect.

When to See a Doctor

It's important to contact your doctor if you experience persistent or severe GLP-1 agonist side effects, such as ongoing nausea, vomiting, abdominal pain, or signs of dehydration. Seek immediate medical attention for symptoms of pancreatitis (severe, persistent upper abdominal pain that may radiate to the back), gallbladder disease (abdominal pain, jaundice), or allergic reactions (swelling, rash, difficulty breathing).

Regular monitoring is essential to ensure the medication remains effective and safe for you. Always consult your doctor before making changes to your medication regimen and report any new or worsening symptoms promptly.

Conclusion

GLP-1 agonists have transformed the management of type 2 diabetes and obesity, offering a multifaceted approach to improving metabolic health. By mimicking the action of the natural GLP-1 hormone, these medications help regulate blood sugar levels, promote weight loss, and potentially reduce the risk of cardiovascular complications. While GLP-1 agonists' side effects can occur, most are manageable with proper use and monitoring. If you have type 2 diabetes or struggle with obesity, talk to your doctor to see if a GLP-1 agonist might be right for you.

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FAQs

1. Are GLP-1 agonists used for weight loss?

Yes, several GLP-1 agonists, such as liraglutide and semaglutide, are FDA-approved for weight loss in adults with obesity or overweight who have at least one weight-related condition, such as high blood pressure or type 2 diabetes. These drugs work by increasing feelings of fullness and decreasing appetite.

2. Is Ozempic a GLP-1 agonist?

Yes, Ozempic is the brand name for semaglutide, a GLP-1 receptor agonist approved for type 2 diabetes and, in higher doses (as Wegovy), for weight management.

3. How long does it take for GLP-1 agonists to work?

GLP-1 agonists typically begin lowering blood sugar soon after the first dose. However, it may take several weeks to see the full GLP-1 agonists' benefits for blood sugar control and several months to achieve maximum weight loss effects.

4. Which drugs are GLP-1 agonists?

Common GLP-1 agonists include exenatide, liraglutide, dulaglutide, semaglutide, and lixisenatide.

5. Can GLP-1 agonists cause low blood sugar?

When used alone, GLP-1 agonists have a low risk of causing hypoglycaemia (low blood sugar). However, the risk may be higher when these medications are combined with insulin or sulfonylureas. Always follow your doctor's instructions and monitor your blood sugar closely.

6. Which is better: Ozempic or Wegovy?

Both Ozempic and Wegovy contain semaglutide, but they are approved for different purposes. Ozempic is used to treat type 2 diabetes, while Wegovy, which contains a higher dose of semaglutide, is specifically approved for weight management. The best choice depends on your individual health needs and goals, as determined by your doctor.

7. Do GLP-1 agonists need to be taken for life?

The duration of GLP-1 agonist therapy depends on individual circumstances. Some people may need to take these medications long-term to manage their type 2 diabetes or maintain weight loss. Others may be able to discontinue or reduce their dosage over time, especially if they make significant lifestyle changes. Consult your doctor to determine the appropriate duration of the treatment for your specific situation.

8. Are GLP-1 agonists safe during pregnancy?

Currently, the safety of GLP-1 agonists during pregnancy has not been established. These medications should be discontinued as soon as a patient becomes aware of a pregnancy. If you are pregnant, planning to become pregnant, or breastfeeding, consult your doctor to discuss alternative treatment options and ensure appropriate management during this time.

References

• https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists
• https://www.ncbi.nlm.nih.gov/books/NBK551568/
• https://www.diabetes.org.uk/about-diabetes/looking-after-diabetes/treatments/tablets-and-medication/glp-1
• https://pmc.ncbi.nlm.nih.gov/articles/PMC12232371/#abstract1
• https://diet.mayoclinic.org/us/blog/2024/how-fast-does-semaglutide-kick-in/