GLP-1 Agonists: How Does Semaglutide Work?

June 19, 2024
semaglutide

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Obesity and type 2 diabetes are major public health concerns worldwide, and effective treatments are in high demand. GLP-1 agonists, a class of medications that mimic the effects of the glucagon-like peptide-1 (GLP-1) hormone, have emerged as promising therapies for both weight management and diabetes treatment. 

One of the most popular GLP-1 agonists is semaglutide, a medication that has gained significant attention for its potential to help individuals achieve considerable weight loss and improve glycemic control.

What is Semaglutide?

Semaglutide is a synthetic version of the human GLP-1 hormone. You might also have heard it referenced as its brand name, Ozempic. It is currently approved for the treatment of type 2 diabetes and, more recently, for chronic weight management in adults with obesity or who are overweight with at least one weight-related comorbidity (cardiovascular disease, high blood pressure, diabetes, etc.).

How Does Semaglutide Work?

Semaglutide works by replicating the actions of the naturally occurring GLP-1 hormone, which plays a crucial role in regulating blood sugar levels and appetite. When semaglutide binds to GLP-1 receptors in the body, it triggers several effects:

  • Increasing insulin secretion from the pancreas: Semaglutide stimulates the release of insulin, which helps lower blood sugar levels by promoting the cells’ glucose uptake.
  • Decreasing glucagon secretion: Glucagon is a hormone that raises blood sugar levels. By reducing glucagon secretion, semaglutide helps maintain better glycemic control.
  • Slowing gastric emptying: Semaglutide slows down the rate at which the stomach empties, leading to a prolonged feeling of fullness and reduced appetite.
  • Increasing feelings of fullness: Semaglutide acts on receptors in the brain that regulate appetite and satiety, leading to a decreased desire to eat and reduced food intake.

This Medication’s Effects on Blood Sugar and Weight

For individuals with type 2 diabetes, semaglutide has been shown to effectively lower blood sugar levels and improve glycemic control. Semaglutide has demonstrated significant reductions in HbA1c levels (a measure of long-term blood sugar control) compared to placebo or other diabetes medications.1

Additionally, semaglutide has proven to be a powerful weight-loss aid. In clinical trials, individuals taking semaglutide for weight management experienced an average weight loss of up to 17% of their initial body weight over 68 weeks. This substantial weight loss can have significant benefits for individuals with obesity, potentially reducing the risk of associated health conditions such as heart disease, stroke, and certain types of cancer.2

Semaglutide Administration and Dosing

Semaglutide is administered via an injection under the skin, typically once a week. For the treatment of type 2 diabetes, the recommended starting dose is 0.25 mg once weekly, which can be gradually increased to a maximum dose of 1 mg once weekly if needed for better glycemic control.

For chronic weight management, the typical starting dose is 0.25 mg once weekly, which can be gradually increased to a maximum dose of 2.4 mg once weekly, depending on the individual’s response and tolerability.

You and your doctor should determine the proper dosage based on your health needs, risk, and history. 

Semaglutide Side Effects and Precautions

Like any medication, semaglutide has many potential side effects. The most common side effects include nausea, vomiting, diarrhea, constipation, and abdominal pain. These gastrointestinal side effects are generally mild to moderate and tend to diminish over time as the body adjusts to the medication.

Additionally, semaglutide should be used with caution in individuals with a history of pancreatitis or severe gastrointestinal disease, as it may increase the risk of these conditions.

Long-term Effects and Safety Considerations

While GLP-1 agonists like semaglutide have shown promising results for weight loss and improving glycemic control, there are some concerns regarding their long-term safety and potential adverse effects with prolonged use.

Thyroid Cancer Risk

Some studies have suggested a potential increased risk of medullary thyroid cancer associated with long-term use of GLP-1 agonists. A study published in 2023 found an increased risk of thyroid cancer by 58% in people who had used GLP-1 drugs for 1-3 years, and a 78% increased risk for those using them for over three years. However, the absolute risk remains low, and further research is needed to establish a causal link.3

Gastrointestinal Side Effects

While gastrointestinal side effects like nausea, vomiting, and diarrhea are common with GLP-1 agonists, there are concerns about more severe gastrointestinal adverse events with long-term use. A 2023 study found that GLP-1 agonists for weight loss were associated with a ninefold higher risk of pancreatitis, a fourfold higher risk of intestinal obstruction, and a threefold higher risk of gastroparesis compared to other weight-loss medications. However, the absolute risks for these complications were less than 1% per year of use.4

Cardiovascular Effects

Some studies have suggested potential cardiovascular benefits of GLP-1 agonists, such as a lower risk of heart failure and hospital admissions for heart attack and stroke. However, more research is needed to determine the long-term cardiovascular effects of these drugs, especially when used for weight loss in non-diabetic populations.5

Need for Updated Guidelines

As GLP-1 agonists are increasingly used for weight management, medical societies are working to develop updated guidelines to help healthcare providers use these medications safely and effectively in clinical practice.

It is important to note that while the potential benefits of GLP-1 agonists for weight loss are promising, their long-term safety profile is still being evaluated. Patients should discuss the risks and benefits with their healthcare providers and closely monitor for any adverse effects during prolonged use.

Weight Loss Should Be Holistic

Semaglutide, a GLP-1 agonist, has emerged as a promising treatment option for both type 2 diabetes and chronic weight management. By mimicking the effects of the naturally occurring GLP-1 hormone, semaglutide can improve glycemic control, promote weight loss, and potentially reduce the risk of associated health conditions.

However, it is crucial to carefully consider the potential side effects and long-term safety concerns associated with semaglutide and other GLP-1 agonists. Patients should consult with their healthcare providers to determine if semaglutide is an appropriate treatment option for their individual needs and to discuss strategies for monitoring and managing any potential adverse effects.

Remember, while semaglutide offers promising benefits, it should be used as part of a comprehensive approach to weight management and diabetes care, which may also include lifestyle modifications, such as a healthy diet and regular exercise.

 

References

  1. Okamoto, A., Yokokawa, H., Nagamine, T., Fukuda, H., Hisaoka, T., & Naito, T. (2021). Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists. Journal of Diabetes and Metabolic Disorders, 20(2), 2121-2128. https://doi.org/10.1007/s40200-021-00899-9 
  2. Chao, A. M., Tronieri, J. S., Amaro, A., & Wadden, T. A. (2022). Clinical Insight on Semaglutide for Chronic Weight Management in Adults: Patient Selection and Special Considerations. Drug Design, Development and Therapy, 16, 4449-4461. https://doi.org/10.2147/DDDT.S365416 
  3. Lisco, G., Tullio, A. D., Disoteo, O., Piazzolla, G., Guastamacchia, E., Sabbà, C., Geronimo, V. D., Papini, E., & Triggiani, V. (2023). Glucagon-like peptide 1 receptor agonists and thyroid cancer: Is it the time to be concerned? Endocrine Connections, 12(11). https://doi.org/10.1530/EC-23-0257
  4. Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. JAMA. 2023;330(18):1795–1797. doi:10.1001/jama.2023.19574 
  5. Parab, P., Chaudhary, P., Mukhtar, S., Moradi, A., Kodali, A., Okoye, C., Klein, D., Mohamoud, I., Olanisa, O. O., & Hamid, P. (2023). Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Cardiovascular Risk Management in Patients With Type 2 Diabetes Mellitus: A Systematic Review. Cureus, 15(9). https://doi.org/10.7759/cureus.45487 
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