GLP-1 receptor agonists are medications that target and treat diabetes and, sometimes, obesity. They include medications such as Ozempic, Byetta, Trulicity, and others. They have been proven to be highly effective in managing blood glucose, or blood sugar, levels and treating diabetes. However, the use of GLP-1s has become increasingly popular, and there have been many scenarios of off-label use of this medication, such as the use of Ozempic for weight loss. Off-label use of GLP-1 agonists could lead to adverse effects and can increase the risk of more severe side effects. Additionally, even prescribed GLP-1s, such as in the case of diabetes and sometimes obesity, could lead to adverse side effects. Thus, patient awareness regarding the side effects of GLP-1 and when to stop using it is crucial. 

Continue reading to learn more about GLP-1 receptor agonists, their side effects, and how to identify any severe side effects that could pose a great risk to overall health and warrant medical intervention. 

What are GLP-1 receptor agonists?

GLP-1 receptor agonists work by mimicking a naturally occurring hormone, GLP-1, which is produced by the small intestine and colon. This hormone stimulates the release of insulin from the pancreas, which can help regulate blood sugar. GLP-1 receptor agonists work through several mechanisms of action, including:

• Insulin secretion: GLP-1 receptor agonists will stimulate the release of insulin, which will regulate and lower blood glucose, or blood sugar, levels 
• Delayed gastric emptying: GLP-1s can essentially slow down digestive processes and delay digestion, which will allow the body to release a lower amount of sugar into the bloodstream. This allows for the regulation of blood glucose levels 
• Inhibiting the release of glucagon: Glucagon is a hormone produced by the pancreas, which raises blood sugar and hinders blood sugar levels from dropping. Thus, the inhibition of glucagon release can prevent an increase in blood sugar levels 
• Appetite suppression: GLP-1 receptor agonists can affect the central nervous system, which can signal the body to feel satiated, and therefore suppress appetite^1,2 

Therapeutic uses

GLP-1 receptor agonists have been proven to be highly effective in the treatment and management of type 2 diabetes mellitus. The mechanisms of action of the medication, such as the stimulation of insulin release and the inhibition of glucagon, help regulate blood sugar levels in people with diabetes. Additionally, the appetite suppression effects and the slower digestion can help manage weight-related problems associated with diabetes and promote weight loss.² Studies have shown that the weight loss effects of GLP-1 receptor agonists can also be beneficial in some cases of obesity, particularly when used in combination with lifestyle modifications such as a balanced diet and exercise. 

Common GLP-Receptor agonists

• Ozempic: Ozempic is a semaglutide used for type 2 diabetes and in some cases, weight loss. It is an injectable medication typically used once a week³ 
• Trulicity: This is a dulaglutide, primarily used for the treatment of type 2 diabetes. Trulicity is an injectable form of medication for diabetes that is typically taken weekly. It helps regulate and manage blood sugar levels⁴ 
• Byetta: Byetta is an exenatide used for the treatment of diabetes, and it comes in the form of an injectable. It is typically used twice a day, and the exact dosages will differ based on the individual, and a doctor may increase the dosage over time⁵ 
• Victoza: Victoza is a liraglutide also used for type 2 diabetes, and it is an injectable that comes in the form of pre-filled pens⁶ 
• Bydureon: This is another form of GLP-1 receptor agonist, and it is an injectable medication used in the treatment of diabetes⁷ 
• Rybelsus: This is an oral semaglutide that comes in the form of tablets and is used to treat diabetes⁸ 

Common side effects: What’s normal?

The use of GLP-1s can often come with some side effects, and most of them usually go away with time. The more common side effects include: 

• Nausea: Nausea, sometimes accompanied by vomiting, is one of the most common gastrointestinal side effects of taking GLP-1s. This nausea could be caused by the effect of GLP-1s on the central nervous system, as well as the delayed gastric emptying and slowed digestive processes caused by the medication⁹ 
• Mild stomach pain: Temporary stomach pain, which is mild, can sometimes be a side effect of taking GLP-1s
• Loss of appetite: The use of GLP-1 receptor agonists can also often result in a loss of appetite, as the medication slows down digestion and sends signals to the brain that stimulate a feeling of fullness. This can keep you satiated for a longer period and will ultimately have an impact on appetite and food intake¹⁰ 
• Constipation: Constipation is another gastrointestinal side effect of taking GLP-1s, and it is one of the more common side effects 
• Injection site reactions: When taking GLP-1 injectable medications, swelling and redness could appear at the injection site. The area of the injection could also be itchy. This is typically a harmless side effect² 

Red Flags: Side effects that could potentially be dangerous

In rarer cases, GLP-1 receptor agonist medications could lead to very serious side effects that can pose a great risk to your health. These side effects are more severe and tend to persist for longer periods. 

Gastrointestinal side effects

The use of GLP-1s could cause some critical gastrointestinal side effects. These typically include:

• Severe vomiting and/or nausea: Although nausea and/or vomiting a common side effects of taking GLP-1s, nausea that is severe and persistent poses a greater risk and could warrant medical intervention
• Severe abdominal pain: Severe abdominal pain, that is also persistent, is a rare side effect of taking GLP-1s. This pain can sometimes be accompanied by vomiting and/or nausea. This side effect of the medication could be an indicator of inflammation of the pancreas, also known as pancreatitis
• Persistent diarrhoea: Persistent or chronic diarrhoea is another severe side effect of taking GLP-1 receptor agonists. This could cause dehydration and can sometimes be accompanied by abdominal pain^9,11 

Pancreatitis

In rare cases, the use of GLP-1s could lead to pancreatitis, which is when the pancreas is inflamed. Symptoms to look out for include severe abdominal pain and severe vomiting. You must speak to a medical professional if these symptoms occur. 

Allergic reactions

GLP-1 receptor agonists can cause severe allergic reactions, and this is sometimes caused by the body forming antibodies against the medication. An allergic reaction at the site of the injection can lead to severe effects and possibly cause anaphylaxis. It is important to look out for symptoms of anaphylaxis, including shortness of breath, a red rash, and tightness of the chest. Signs of an allergic reaction that are not as severe but still warrant medical intervention include redness and itching at the site of the injection.² 

When to seek medical intervention

You must contact your healthcare provider if you experience any severe symptoms, such as abdominal pain, severe nausea and/or vomiting, signs of pancreatitis, and signs of an allergic reaction. Additionally, if any symptoms interfere with your day-to-day life and your ability to complete daily activities, you must speak to a professional. 

GLP-1 alternatives

In some cases, switching to a different GLP-1 receptor agonist medication can still be a viable option. GLP-1 medications vary in terms of dosage, formulation, and duration of action, which means that an individual can respond differently depending on the exact GLP-1 being used. However, if switching to another GLP-1 is not a suitable option, there are other alternatives for managing diabetes and obesity. These include: 

• Alternative medications: SGLT2 inhibitors can be a suitable treatment for type 2 diabetes. They target the kidneys to remove excess sugar and ultimately reduce blood glucose levels.¹² D-PP4 inhibitors are also another therapeutic option for treating and managing type 2 diabetes, by preventing the breakdown of incretin hormones. This promotes the release of insulin and the lowering of blood sugar levels¹³ 
• Lifestyle changes: Maintaining a balanced diet, frequently exercising, and managing weight are all important factors in effectively managing type 2 diabetes and obesity  

Summary

GLP-1 receptor agonists are effective in treating and managing type 2 diabetes and promoting weight loss, and can offer various benefits. However, these medications also have significant risks, which can sometimes be severe and require medical intervention. Recognising red flags and understanding when to stop the use of the medication and seek help from a professional is crucial for safe treatment. Being proactive in managing your health and looking out for these red flags can help significantly with ensuring a successful treatment and reduce the risk of adverse side effects.