Introduction

Have you come across Semaglutide (Ozempic®, Rybelsus®) as a treatment marketed for weight loss? Commonly known for the management of diabetes, semaglutide works in a way different from other diabetes medications, so it can be used for several other medical purposes. To better understand how this works, we will break down the mechanism of semaglutide’s action and how it can affect your body, so that you can make informed choices about the use of this medication.

How does Semaglutide work?

Semaglutide belongs to a class of drugs named Glucagon-Like Peptide-1 (GLP-1) analogues. GLP-1 is a gut-derived hormone that aids in the regulation of glucose levels. These medications are not usually the first-line treatment for diabetes, but have proven to be an effective alternative, with the added benefits of weight loss and reduction of cardiovascular risk in diabetic individuals.¹ 

Semaglutide is an optimised form of GLP-1 analogue, as it has a very similar chemical structure and amino acid sequence to human/intrinsic GLP-1 (around 94% similarity). This lends the drug its high efficacy in research trials and clinical practice. As it has a plasma half-life of approximately one week, semaglutide can be given once weekly, rather than daily, in contrast to other medications for diabetes and weight loss.

The natural mechanism of GLP-1 release is that once food is ingested, it will trigger the release of GLP-1 from the small intestines.² GLP-1 has several functions, such as:

• Decreasing appetite by acting on the brain
• Reducing/slowing down gastric emptying (the movement of food from the stomach to the small intestine) by acting on the stomach
• Inducing insulin secretion via the pancreas and concurrently inhibiting glucagon secretion

It is the last bullet point in particular that influences glucose regulation. GLP-1 analogues and receptor agonists will mimic the same function and effects of human GLP-1, thereby further decreasing appetite, slowing gastric emptying and reducing blood glucose levels, particularly after meals (when glucose levels are expected to peak). 

The reason this medication has been used for the aid of weight loss is that it has several functions, besides glucose management as we’ve mentioned earlier. Semaglutide can increase satiety, reduce fat deposition, and reduce fat absorption from the gut. The overall decrease in calorie intake would also lead to weight loss.

Indications for use of semaglutide

As mentioned earlier, Semaglutide is licensed for the treatment of diabetes (commonly type 2 diabetes) and managing weight. The term weight management includes both weight loss and maintenance. 

According to the National Institute of Health and Care Excellence (NICE), semaglutide can be prescribed for a maximum of 2 years, and the treatment should be initiated and monitored by specialist weight or diabetes services.³ Eligible patients should have a body mass index (BMI) of at least 35 kg/m² or a BMI between 30 and 34.9 kg/m² and meet the criteria for specialist weight management referral. 

It is essential to note that for any patient who is started on semaglutide in the NHS and has lost less than 5% of their initial weight after 6 months of treatment, semaglutide is likely to be stopped (according to NICE recommendations). These criteria and recommendations will vary across different countries and healthcare systems. In some countries you may have access to certain medications without prescriptions from specialist physicians, so caution should be exercised.

Forms of semaglutide

Semaglutide is sold under different brands. Perhaps the most commonly heard of is Ozempic®, but there is also Rybelsus® and Wegovy®. These medications are available as tablets and injections in pre-filled pens.⁴

Before starting any treatment, ensure that you read the manufacturer’s information leaflet, found inside the packaging. Also, refer to your doctor or diabetes clinic for advice on which medication to use and how to use it appropriately. 

The use of injection pens should be demonstrated by a trained professional. Each pen provides a single dose, so you cannot use the same pen several times. The injection is given ‘subcutaneously’ – this means that you will only inject in the fatty tissue of different areas of the body, rather than muscle, veins or bones. Examples of areas to inject into include the abdomen (particularly the lower abdomen, where you might have more fatty tissue and can pinch a section of skin easily), upper arms, and thighs. The injection can be given at any time of day, but you are advised to take the next injection on the same day, a week later. There are several rules on missed doses- if this applies to you, ask your doctor or pharmacist for support with when to take your medication.

For semaglutide oral tablets, you may be prescribed different doses for different durations. The initial dose is one 3 mg tablet taken daily for one month. This is followed by one 7 mg tablet taken daily for at least another month. You are advised to take your dose around the same time each day (unlike injection pens, where the timing of the day does not matter). Drink plenty of water with your tablet and ensure that this is taken on an empty stomach, at least two hours before your meal. If you miss a dose, do not take two doses/tablets together to make up for a missed one, and inform your clinician/pharmacist.

Side effects

It is common for semaglutide to cause gastrointestinal upset, which may include diarrhoea, nausea, bloating and abdominal pain. It is important to be aware of the risk of hypoglycaemia (low blood sugar), as this can cause someone to become very unwell. Look out for signs or symptoms of feeling shaky, anxious, cold, looking pale, feeling dizzy, palpitations and sweating. 

In cases where the person is still conscious and can swallow, hypoglycaemia can be avoided or treated by having something sugary followed by a snack containing carbohydrates. For example, candy or sugary drinks, followed by toast/sandwich. 

Another potential risk of semaglutide, although not as common, is pancreatitis. This may present as persistent or severe abdominal pain with vomiting. This requires urgent medical attention.

Summary

GLP-1 analogues, like semaglutide, increase the secretion of insulin, a hormone made naturally by the body, which helps to regulate glucose levels. This is key for its use as a medication for diabetes.  Given the other functions of GLP-1 analogues and agonists, this medication can also be used for weight management.