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In a world where, according to WHO, 1 in 8 adults live with obesity, the search for effective weight loss solutions continues. Among the latest advancements in pharmacotherapy for weight management are GLP-1 agonists which have shown promising results in aiding weight loss. 

In this post, we delve into the mechanism of action of GLP-1 agonists, their effectiveness, potential benefits and risks, and prescribing criteria.

What Are GLP-1 Agonists?

GLP-1 (glucagon-like peptide-1) agonists are a class of medications designed to mimic the action of the natural hormone GLP-1. This hormone is produced in the gut in response to food intake. GLP-1 plays an essential role in regulating blood sugar levels, insulin secretion, and satiety. 

These medications were initially developed for the treatment of type 2 diabetes, but are also used for weight loss. They are typically administered via subcutaneous injections (into the tissue under the skin) and are used along with lifestyle modifications, such as a balanced diet and regular exercise.

How Do They Work for Weight Loss?

The mechanism of action of GLP-1 agonists for weight loss is multifaceted. First, they have profound effects on appetite regulation and satiety. When GLP-1 receptors in the brain are activated, they send signals that reduce appetite and increase feelings of fullness, leading to reduced food intake. This appetite-suppressing effect is thought to be mediated by the hypothalamus, a region of the brain involved in regulating hunger and energy balance.

Furthermore, GLP-1 agonists slow down gastric emptying, which prolongs the time it takes for food to move through the digestive tract. This delay in gastric emptying contributes to feelings of fullness and satiety, further reducing appetite.

By targeting multiple aspects of appetite regulation and metabolism, GLP-1 agonists offer a comprehensive approach to weight management. Moreover, these medications enhance insulin sensitivity, facilitating glucose uptake by cells and potentially reducing fat accumulation.

Effectiveness of GLP-1 Agonists

The effectiveness of GLP-1 agonists in promoting weight loss has been well-documented through numerous clinical trials and research reviews. These medications have shown significant efficacy in helping individuals achieve meaningful reductions in body weight, particularly when used in conjunction with lifestyle modifications. 

Studies have shown that individuals using these medications alongside improved lifestyle experience greater weight loss compared to those on placebo or conventional weight loss interventions alone. It's important to note that the results vary among individuals and may depend on the particular GLP-1 agonist medication, baseline weight, adherence to treatment, and concurrent lifestyle changes. To learn how to make this process more effective in your case, consider consulting with an experienced doctor for weight loss online.

GLP-1 Drugs Approved For Weight Loss

Currently, several GLP-1 agonists have received approval from the U.S. Food and Drug Administration (FDA) for weight management. Among the most notable GLP-1 drugs for weight loss are liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound). They are commonly available as subcutaneous injections and are typically prescribed for individuals with obesity or overweight who have failed to achieve weight loss through diet and exercise alone.

Overview of GLP-1 Medications

Some of the commonly prescribed GLP-1 medications for weight management include:

• Saxenda (liraglutide): It was originally developed as a treatment for type 2 diabetes, but was later approved by the FDA for chronic weight management in adults with obesity or overweight. Clinical trials have shown that Saxenda can lead to significant weight loss when used in conjunction with a reduced-calorie diet and increased physical activity. Saxenda's recommended dose is 3 mg daily, taken at any time, irrespective of meals. It is administered subcutaneously in the abdomen, thigh, or upper arm at 0.6 mg daily, increasing weekly until reaching 3 mg.
• Wegovy (semaglutide): It is a newer GLP-1 agonist that has garnered attention for its potent weight loss effects. In double-blind trials, semaglutide has demonstrated superiority over other weight loss medications and placebo in achieving substantial reductions in body weight. It is administered weekly on the same day, at any time, with or without food, via subcutaneous injection in the abdomen, thigh, or upper arm. It is usually started at 0.25 mg weekly and may be gradually increased to 2.4 mg maintenance dose. The once-weekly injectable formulation of semaglutide offers convenience and improved adherence compared to daily dosing regimens.
• Zepbound (tirzepatide): It is the newest FDA-approved once-weekly subcutaneous injectable medication that works also as a glucose-dependent insulinotropic peptide (GIP) receptor agonist along with GLP-1 receptor agonist. It effectively lowers HbA1c levels and promotes weight loss, surpassing other medications. As per a 72-week double-blind controlled trial, patients given weekly subcutaneous tirzepatide had significant, lasting weight loss versus placebo. The initial dose is typically 5 mg, with a maximum dose of 15 mg.

Discuss the dosage and other instructions with your healthcare provider before starting any medication.

Prescribing Criteria 

GLP-1 agonists may be beneficial and prescribed for individuals who have:

• A body mass index (BMI) of 30 kg/m2 or higher.
• A BMI of 27 kg/m2 or higher in case of any obesity-related comorbidities, such as type 2 diabetes or cardiovascular diseases like hypertension.

Individuals planning to start GLP-1 agonist therapy should have a willingness to commit to lifestyle changes, including dietary modifications and increased physical activity. Also, remember that your doctor can best judge if GLP-1 agonists are the most helpful choice of weight loss drugs for you.

Who Should Not Take GLP-1 Agonists?

While GLP-1 agonists are generally well-tolerated, there are certain contraindications and precautions to consider, such as:

• History of pancreatitis, diabetic retinopathy, thyroid cancer. 
• Pregnancy or breastfeeding.
• Concurrent use with an insulin secretagogue or insulin may raise the risk of hypoglycemia. 

Also, patients with renal impairment should monitor kidney function when taking these medications. 

Potential Side Effects

Common side effects of GLP-1 agonists, particularly during the initial weeks of weight loss treatment, include: 

• Nausea 
• Vomiting 
• Diarrhea
• Headache
• Constipation
• Decreased appetite
• Pain in the right or middle upper stomach area
• Fatigue
• Dizziness
• Indigestion
• Injection site reactions (e.g., injection site rash, erythema)

Conclusion

GLP-1 agonists represent a promising pharmacological approach to weight management, offering significant benefits for individuals struggling with obesity or being overweight. By strengthening the body's natural mechanisms for regulating appetite and metabolism, these medications can help facilitate sustainable weight loss when combined with lifestyle changes. With further research and development, GLP-1 agonists may continue to play an important role in combating the global epidemic of obesity and improving overall health.

References

• World Health Organization. (2024). Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
• Vosoughi, K., Salman Roghani, R., Camilleri, M. (2022). Effects of GLP-1 agonists on proportion of weight loss in obesity with or without diabetes: Systematic review and meta-analysis. https://doi.org/10.1016/j.obmed.2022.100456
• Ard, J., Fitch, A., Fruh, S. et al. (2021). Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists. https://doi.org/10.1007/s12325-021-01710-0
• Jensterle, M., Rizzo, M., Haluzík, M. et al. (2022). Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. https://doi.org/10.1007/s12325-022-02153-x
• Iqbal, J., Wu, H. X., Hu, N. et al. (2022). Effect of glucagon-like peptide-1 receptor agonists on body weight in adults with obesity without diabetes mellitus-a systematic review and meta-analysis of randomized control trials. https://doi.org/10.1111/obr.13435
• Popoviciu, M.-S., Păduraru, L., Yahya, G. et al. (2023). Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials. https://doi.org/10.3390/ijms241310449
• Mehta, A., Marso, S. P., and Neeland, I. J. (2017). Liraglutide for weight management: a critical review of the evidence. https://doi.org/10.1002/osp4.84
• Wilding, J. P. H., Batterham, R. L., Calanna, S. et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. https://doi.org/10.1056/NEJMoa2032183
• Jastreboff, A. M., Aronne, L. J., Ahmad, N. N. et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. https://doi.org/10.1056/NEJMoa2206038
• Sun, F., Chai, S., Li, L. et al. (2015). Effects of glucagon-like peptide-1 receptor agonists on weight loss in patients with type 2 diabetes: a systematic review and network meta-analysis. https://doi.org/10.1155/2015/157201
• Ansari, H. U. H., Qazi, S. U., Sajid, F. et al. (2024). Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight and Cardiometabolic Parameters in Individuals With Obesity and Without Diabetes: A Systematic Review and Meta-Analysis. https://doi.org/10.1016/j.eprac.2023.11.007

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