When trying to lose weight, most people are looking for a quick and easy way to achieve this goal.  While the foundation of every weight loss program includes eating fewer calories and doing more physical activity (to burn more calories), sometimes people struggle to lose weight even when they are already doing both of these things.  This challenge often leads people to consider either pharmaceutical options and/or bariatric surgery.

Pharmaceutical weight loss injections in the UK all contain an analogue of glucagon-like peptide-1 (GLP-1), which is sometimes called a GLP-1 receptor agonist.  This means the weight loss injections contain a chemical which activates the GLP-1 receptors in the body.  Activating the GLP-1 receptors in the body can reduce blood glucose levels and create feelings of fullness and satiety.

The GLP-1 analogues available in the UK are semaglutide and liraglutide.  Both compounds are marketed under two different licenses – one for managing blood glucose levels for people with type 2 diabetes, and a separate license to allow them to be used specifically for weight loss (usually at a different dose).

The GLP-1 analogues marketed for weight loss effect the body in three ways:

• They make the stomach empty slower – so someone feels satisfied with smaller amounts of food, which helps them eat less and creates a calorie deficit that can lead to weight loss;
• They signal the brain (primarily the hypothalamus and hindbrain) that there is food in the stomach, which helps decrease appetite; and
• Certain brands can help reduce food cravings as well.

The body does produce its own GLP-1, but the synthetic versions are designed to breakdown slower and stay in the body longer than the natural version.  This allows them to reduce hunger for most of the day.

Before considering these injections, clients need to think carefully about the following:

• Is excessive or uncontrolled physical hunger the underlying problem?  People eat for many reasons that have nothing to do with physical hunger, such as to socialise, for comfort or for impulsive reasons.  These drugs will not help if the person is already ignoring their body’s signals for physical hunger and fullness (or if hunger is not the root cause of the problem).
• Has there been any damage to the hypothalamus or hindbrain due to a brain injury?  If so, these drugs are unlikely to work, because they act on the hypothalamus and hindbrain to influence appetite.1, 2
• What is the long-term weight management plan?  Once these injections are discontinued, people tend to regain 2/3 of the weight they lost over the next year, presumably because appetite and/or eating habits return to pre-injection levels.1, 3. However, people still managed to retain at least a 5-6% weight loss, even once the weight regain is factored in.3
• Do the benefits outweigh the risks/side effects?

1.  Semaglutide 

(e.g. Wegovy® is the brand licensed for weight loss in the UK) 2, 4

How it works

• Semaglutide is an injectable, once-WEEKLY medication that works primarily by suppressing appetite.
• In addition to making the stomach empty slower and reducing appetite, semaglutide can result in fewer food cravings and help someone endure food cravings, by modifying the reward system (dopamine) in the brain.
• Semaglutide reduces blood glucose levels, by increasing the glucose-dependent secretion of insulin and reducing the secretion of glucagon.
• On average, adults on semaglutide lose 9.6 – 16% of their body weight in 68 weeks.  This is compared to adults on a reduced-calorie diet who were also advised to do 100-150 minutes of physical activity per week, who lost only 2.4 – 5.7% of their body weight in the same period.

Who is it for?

• Semaglutide is licensed for use in:
  • ADULTS with a body mass index (BMI) of 30kg/m2 or higher; OR
  • ADULTS with a BMI of 27kg/m2 in the presence of at least one weight-related comorbid condition (e.g. hypertension, type 2 diabetes, dyslipidemia).
  • It is NOT licensed for use in paediatric clients.
• It is not recommended in someone who is pregnant or who has multiple endocrine neoplasia syndrome type 2.  It is also not recommended if someone has had a previous hypersensitivity to semaglutide.
• This medication is currently being reviewed by the National Institute for Clinical Excellence to decide if it will be offered through the NHS for weight loss.

Risks/side effects/warnings/precautions

• The most common side effects (>5%) include: nausea, diarrhoea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distention, eructation (belching), hypoglycaemia in patients with type 2 diabetes, flatulence, gastroenteritis and gastroesophageal reflux.
• Warnings: risk of thyroid C-cell tumours; acute pancreatitis; acute gallbladder disease; hypoglycaemia; acute kidney injury; hypersensitivity reactions; suicidal behaviour and ideation; heart rate increase; and diabetic retinopathy complications in patients with type 2 diabetes.
• Semaglutide increases the risk of hypoglycaemia, if used in combination with insulin or insulin secretagogues.
• Semaglutide delays gastric emptying, which may impact the absorption of oral medications administered at the same time.

Additional considerations

• Treatment with semaglutide should be discontinued at least 2 months before a planned pregnancy.
• People with type 2 diabetes should monitor their blood glucose levels while taking semaglutide.

Where can you get it?

• It is currently only available through private prescription, so a private GP, endocrinologist or rehabilitation consultant would need to issue the prescription.
• The NHS is still considering whether this is something they will fund and what the criteria will be to have this covered.

2.  Liraglutide

(e.g. Saxenda® is the brand licensed for weight loss in the UK) 5, 6, 7

How it works

• Liraglutide is an injectable, once-DAILY medication that works primarily by suppressing appetite. It is chemically similar to semaglutide (mentioned above), but the two medications are not identical.
• Liraglutide reduces blood glucose levels by increasing the glucose-dependent secretion of insulin and reducing the secretion of glucagon. Liraglutide does not adversely affect glucagon secretion in response to low blood glucose levels.
• On average, adults on liraglutide lose 6.7 – 9.2% of their body weight in 56 weeks (compared to adults on a low-calorie diet who lose 0 – 3% of their body weight in the same period).
• On average, children (12-17 years) on liraglutide reduce their BMI by 4.29% over 56 weeks (compared to children in the placebo group who increase their BMI by 0.35%).

Who is it for?

• Liraglutide is licensed for use in:
  • ADULTS with a body mass index (BMI) of 30kg/m2 or higher; OR
  • ADULTS with a BMI of 27kg/m2 in the presence of at least one weight-related comorbid condition (e.g. hypertension, type 2 diabetes, dyslipidaemia); OR
  • PAEDIATRIC patients aged 12 years and older with a body weight above 60kg AND a BMI cut-off for obesity.
• It is not recommended in anyone who is pregnant, has a hypersensitivity to liraglutide, or with multiple endocrine neoplasia syndrome type 2 and/or with a personal or family history of medullary thyroid carcinoma.
• To get this medication through the NHS, there are different criteria (see below).

Risks/side effects/warnings/precautions

• The most common side effects (>5%) include: nausea, diarrhoea, constipation, vomiting, injection site reaction, headache, hypoglycaemia, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, upper abdominal pain, pyrexia (fever) and gastroenteritis.
• Warnings: risk of thyroid C-cell tumours; acute pancreatitis; acute gallbladder disease; hypoglycaemia (if used with insulin or an insulin secretagogue); renal impairment; hypersensitivity reactions; suicidal behaviour and ideation; and heart rate increase.
• Liraglutide delays gastric emptying, which may impact the absorption of oral medications administered at the same time.

Additional considerations

• Treatment with liraglutide should be discontinued in adults if the client has not achieved a 4% decrease in body weight within 16 weeks of using the full dose.  It should be discontinued in children if they haven’t achieved at least a 1% weight loss within 12 weeks.
• People with type 2 diabetes should monitor their blood glucose levels while taking liraglutide.

Where can you get it?

• It is currently available through private prescription, so a private GP, endocrinologist or rehabilitation consultant would need to issue the prescription.
• It is also available through the NHS, but only if the following (slightly different) criteria are met.  To be eligible for it through the NHS all of these conditions apply: 8, 9
  • The person must have a BMI of 35 kg/m2 or more, or a BMI of 32.5 kg/m2 or more if they are of south Asian, Chinese, black African or African-Caribbean origin;
  • The person has non-diabetic hyperglycaemia (high blood glucose);
  • The person is at high risk of heart problems such as heart attacks and strokes, for example because they have hypertension;
  • It must be prescribed by a specialist multidisciplinary tier 3 weight management service; and
  • The company provides the medication according to the commercial arrangement.

Before someone considers weight loss injections, they should be seen by a dietitian who will complete a comprehensive review of a client’s food intake, activity levels, medical history and food-related behaviours, to determine the root cause of someone’s weight-related problem.  This can help clients decide whether a weight loss injection should be considered.

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