Long-Term Effects of Semaglutide: What You Need to Know

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has gained significant attention for its efficacy in managing type 2 diabetes and aiding weight loss. Semaglutide, originally developed and approved for diabetes treatment, has also been marketed under the brand name Wegovy for chronic weight management. Despite the well-documented short-term benefits of semaglutide in controlling blood sugar levels and promoting weight loss, concerns persist regarding its long-term effects. This article delves into the potential long-term impacts of semaglutide, how to mitigate these risks, and the best practices for starting the medication based on age, weight, and other factors.

The Mechanism of Semaglutide

Semaglutide works by mimicking the action of the GLP-1 hormone, which increases insulin secretion, suppresses glucagon release, and slows gastric emptying. These actions collectively help to lower blood sugar levels and promote a feeling of fullness, which can lead to weight loss.

Proven Long-Term Effects and Side Effects

Gastrointestinal Issues

• Overview: The most common side effects of semaglutide, especially in the initial stages of treatment, are gastrointestinal in nature. These include nausea, vomiting, diarrhoea, and constipation. For most people, these symptoms are temporary and tend to subside as the body adjusts to the medication.
• Long-Term Impact: For some individuals, these gastrointestinal symptoms may persist. Chronic diarrhoea or constipation can lead to dehydration, electrolyte imbalance, and nutritional deficiencies if not managed properly.
• Common side effects: nausea, vomiting, diarrhoea, and constipation are the most common gastrointestinal side effects. These symptoms are usually more pronounced at the start of treatment and tend to subside over time.
• How to Avoid: Begin with the lowest possible dose and gradually increase as tolerated. Staying hydrated, eating smaller meals, and avoiding high-fat foods can help reduce these symptoms.

Pancreatitis

• Overview: Pancreatitis, or pancreas inflammation, is a known but rare side effect of GLP-1 receptor agonists like semaglutide.
• Risk: There have been reports of pancreatitis (inflammation of the pancreas) in patients using GLP-1 receptor agonists, including semaglutide. This condition can be severe and requires immediate medical attention.
• Long-Term Impact: While the incidence of pancreatitis with semaglutide is low, the risk remains significant because pancreatitis can lead to serious health complications, including pancreatic cancer.
• How to Avoid: Patients with a history of pancreatitis should avoid semaglutide. If you experience severe abdominal pain, especially if it radiates to your back, seek medical attention immediately.

Thyroid C-cell Tumours

• Overview: Animal studies have shown that semaglutide can cause an increased risk of thyroid C-cell tumors. However, humans have not conclusively proven this risk.
• Risk: Animal studies have shown an increased risk of thyroid C-cell tumours with long-term use of semaglutide. Although humans have not conclusively proven this risk, it remains a concern.
• Long-Term Impact: Although there’s no clear evidence linking semaglutide to thyroid cancer in humans, the FDA advises caution, especially in individuals with a history of thyroid cancer or a family history of multiple endocrine neoplasia syndrome type 2 (MEN2).
• How to Avoid: Regular monitoring of thyroid function is recommended, particularly for those with a family history of thyroid cancer. Patients with a history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome type 2 should use semaglutide with caution.

Cardiovascular Effects

• Overview: Semaglutide has been shown to have cardiovascular benefits, including reducing the risk of major adverse cardiovascular events (MACE) in people with type 2 diabetes. However, there is a need to understand the long-term impact on heart health in people without diabetes.
• Long-Term Impact: Semaglutide’s cardiovascular benefits are encouraging, but more research is required to understand its long-term effects, especially for those who use it primarily for weight loss.

Gallbladder Disease

• Overview: Semaglutide has been associated with an increased risk of gallbladder disease, including gallstones and cholecystitis.
• Risk: Semaglutide may increase the risk of gallbladder disease, including gallstones and cholecystitis (inflammation of the gallbladder).
• Long-Term Impact: Long-term use of semaglutide may increase the risk of gallbladder disease, especially in individuals with a history of such conditions.
• How to Avoid: Be vigilant for symptoms of gallbladder disease, such as upper abdominal pain, nausea, and jaundice. Long-term users may benefit from regular ultrasound monitoring.

Kidney Function

• Overview: There have been reports of acute kidney injury in people using semaglutide, especially in those with pre-existing kidney conditions or dehydration.
• Long-Term Impact: To prevent potential damage, long-term semaglutide users should regularly monitor their kidney function.

Hypoglycemia

• Risk: Although semaglutide itself has a low risk of causing hypoglycemia, the risk increases when used in combination with other diabetes medications like insulin or sulfonylureas.
• Long-Term Impact: Chronic hypoglycemia can lead to neurological damage, cardiovascular events, and reduced quality of life.
• How to Avoid: Monitor blood glucose levels regularly, especially if you are using other medications that lower blood sugar. Adjusting the dosage of these medications under the guidance of a healthcare provider can help mitigate this risk.

Avoiding Long Term Side Effects

To minimise the risks associated with long-term use of semaglutide, consider the following strategies:

1. Gradual Dose Escalation: Starting with a low dose and gradually increasing it can help the body adjust to the medication, reducing the risk of gastrointestinal side effects.
2. Hydration and Electrolyte Balance: Maintaining adequate hydration and monitoring electrolyte levels can prevent complications from gastrointestinal side effects like diarrhoea and vomiting.
3. Regular Monitoring: Regular medical check-ups, including blood tests and imaging studies, can help detect any adverse effects early, particularly those related to the pancreas, thyroid, kidneys, and gallbladder.
4. Individualised Treatment Plans: Tailoring the treatment plan with the help of our team of experts.

Recommended dosage based on age, gender, and weight

The dosage of semaglutide varies depending on the intended use (diabetes management vs. weight loss) and individual factors like age, gender, and weight. The goal is to find the lowest effective dose that provides the desired benefits while minimising side effects.

1. Dosage for Adults

• Standard Starting Dose: Both Ozempic and Wegovy typically start at 0.25 mg once weekly and gradually increase to 1 mg (Ozempic) or 2.4 mg (Wegovy) per week over several weeks.
• Weight Adjustment: Heavier individuals may require higher doses to achieve the same therapeutic effects, while lighter individuals may achieve results with lower doses.
• Gender Considerations: There is no specific dosage adjustment based on gender, but women may be more prone to gastrointestinal side effects, so a slower titration may be beneficial.

2. Dosage for older adults

• Lower Initial Dose: Older adults, especially those over 65, should start at the lowest possible dose and increase it more slowly, as they may be more susceptible to side effects.
• Monitoring: Regular monitoring for renal function and signs of dehydration is crucial, as older adults are more prone to these issues.

3. Special Considerations for Young Adults and Adolescents

• Exercise Caution: We typically do not recommend the use of semaglutide in individuals under the age of 18, due to the lack of established safety and efficacy in this age group. In some cases, however, doctors may prescribe it off-label under careful monitoring.
• Lower Dosages: To minimise side effects, use lower starting doses and a slower titration schedule.

Precautions Before Starting Semaglutide

Before starting semaglutide, it’s important to undergo a thorough medical evaluation to ensure it’s appropriate for you. Consider the following precautions:

1. Medical History: Disclose your full medical history to your healthcare provider, especially if you have a history of pancreatitis, thyroid cancer, gallbladder disease, or kidney problems.
2. Current Medications: Provide a complete list of current medications to avoid potential drug interactions, particularly with other diabetes medications.
3. Regular Monitoring: Commit to regular follow-up appointments to monitor blood glucose levels, kidney function, thyroid function, and other relevant health parameters.
4. Lifestyle Changes: While semaglutide can aid in weight loss, it is most effective when combined with a healthy diet and regular physical activity. Establish a sustainable lifestyle plan with the assistance of your healthcare provider.

Our Conclusion

Semaglutide is a powerful medication with significant benefits for both diabetes management and weight loss. However, its long-term use requires careful monitoring and a personalised approach to dosing to minimise potential side effects. By understanding the risks and taking appropriate precautions, you can use semaglutide safely and effectively as part of your long-term health strategy.