Incretin mimetics for weight loss, also known as GLP-1 receptor agonists, represent a significant advancement in obesity treatment. Originally developed for type 2 diabetes, medicines such as semaglutide (Wegovy) and liraglutide (Saxenda) have demonstrated substantial weight reduction when combined with lifestyle changes. These injectable treatments work by mimicking natural gut hormones that regulate appetite, slow stomach emptying, and enhance feelings of fullness. In the UK, specific formulations are licensed for weight management and available through specialist NHS services for eligible patients, though access remains limited by strict criteria and regional capacity.

What Are Incretin Mimetics and How Do They Work?

Incretin mimetics, also known as glucagon-like peptide-1 (GLP-1) receptor agonists, are a class of medicines originally developed for managing type 2 diabetes that have demonstrated significant efficacy in promoting weight loss. These medicines work by mimicking the action of naturally occurring incretin hormones, particularly GLP-1, which are released from the intestine in response to food intake. Some newer agents, such as tirzepatide, are dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonists, combining the effects of both incretin hormones.

The mechanism of action involves several physiological pathways that contribute to weight reduction. GLP-1 receptor agonists bind to GLP-1 receptors in the brain, particularly in areas that regulate appetite and satiety, leading to reduced hunger and increased feelings of fullness after eating. This can reduce appetite and energy intake. Additionally, these medicines slow gastric emptying, meaning food remains in the stomach for longer periods, which prolongs the sensation of fullness and reduces the frequency of eating. This effect may diminish somewhat with continued use.

Beyond appetite regulation, incretin mimetics influence glucose metabolism by enhancing insulin secretion in a glucose-dependent manner and suppressing glucagon release when blood glucose levels are elevated. This dual action helps stabilise blood sugar levels whilst supporting weight loss. The glucose-dependent mechanism means that these medicines carry a lower risk of hypoglycaemia compared to some other diabetes treatments when used alone. These medicines are not indicated for type 1 diabetes or diabetic ketoacidosis.

Clinical trials have demonstrated that incretin mimetics can lead to substantial weight loss when combined with lifestyle modifications, though efficacy varies by agent and dose. Semaglutide 2.4 mg (Wegovy) achieved average weight reductions of approximately 12–15% of body weight in the STEP clinical trial programme, whilst liraglutide 3 mg (Saxenda) typically achieves around 5–8% weight loss. Individual responses vary considerably based on factors including baseline weight, adherence to treatment, and concurrent lifestyle changes. The weight loss effect appears to be sustained as long as treatment continues, but weight regain commonly occurs after stopping the medicine.

Which Incretin Mimetics Are Used for Weight Management in the UK?

In the UK, specific formulations of incretin mimetics have received regulatory approval from the Medicines and Healthcare products Regulatory Agency (MHRA) for weight management. Semaglutide 2.4 mg (marketed as Wegovy) is licensed specifically for weight management in adults with a body mass index (BMI) of 30 kg/m² or greater, or 27 kg/m² or greater in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes, or obstructive sleep apnoea. Wegovy is administered as a once-weekly subcutaneous injection, with gradual dose escalation to the maintenance dose of 2.4 mg weekly.

Liraglutide 3 mg (Saxenda) was the first GLP-1 receptor agonist licensed in the UK specifically for weight management and is administered as a daily subcutaneous injection. It is indicated for adults with a BMI of 30 kg/m² or above, or 27 kg/m² or above with weight-related complications. Saxenda is also licensed for adolescents aged 12 years and above with obesity. The maintenance dose is 3 mg daily. Liraglutide at a lower dose (Victoza) remains licensed for type 2 diabetes management, and the weight loss observed with diabetes formulations, whilst beneficial, is typically less pronounced than with the higher-dose weight management formulation.

Other GLP-1 receptor agonists such as dulaglutide (Trulicity) and exenatide (Byetta, Bydureon) are licensed for type 2 diabetes management in the UK and may produce modest weight loss as a secondary benefit, but they are not specifically licensed for weight management as a primary indication. Tirzepatide (Mounjaro), a dual GIP/GLP-1 receptor agonist, is licensed for type 2 diabetes in the UK and has shown substantial weight loss in clinical trials; its weight management indication status should be confirmed with current MHRA licensing and NICE guidance. Oral semaglutide (Rybelsus) is not licensed for weight management in the UK.

It is important to note that regulatory licensing differs from NHS funding decisions, which are determined by NICE Technology Appraisals. The choice of agent depends on individual patient factors, licensing status, NICE recommendations, availability, and clinical appropriateness as determined by a healthcare professional.

Side Effects and Safety Considerations

Incretin mimetics are generally well-tolerated, but patients should be aware of potential adverse effects before commencing treatment. Gastrointestinal symptoms represent the most common side effects, affecting a significant proportion of users, particularly during the initial weeks of treatment or following dose escalations. These include:

• Nausea (affecting up to 40–50% of patients initially)

• Vomiting and diarrhoea

• Constipation

• Abdominal pain or discomfort

• Reduced appetite (which, whilst contributing to weight loss, can occasionally be excessive)

These gastrointestinal effects typically diminish over time as the body adjusts to the medicine, and gradual dose titration helps minimise their severity. Patients should be advised to eat smaller, more frequent meals and avoid high-fat foods, which may exacerbate symptoms. Persistent severe vomiting or signs of dehydration require prompt medical assessment, as dehydration can affect kidney function, particularly in those with pre-existing renal impairment.

More serious but rare adverse effects require careful monitoring. Acute pancreatitis has been reported in patients taking GLP-1 receptor agonists. Patients should be counselled to seek immediate medical attention and stop treatment if they experience severe, persistent abdominal pain, particularly if radiating to the back and accompanied by vomiting. Additionally, animal studies have shown thyroid C-cell tumours in rodents treated with GLP-1 receptor agonists. Whilst no definitive link has been established in humans, patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 should discuss the potential risks with their doctor before starting treatment. Refer to the individual product Summary of Product Characteristics (SmPC) for specific precautions.

Gallbladder disease, including gallstones (cholelithiasis) and inflammation of the gallbladder (cholecystitis), has been associated with GLP-1 receptor agonists. Patients should seek medical advice if they experience symptoms such as right upper abdominal pain, fever, or jaundice. In people with type 2 diabetes, rapid improvement in blood glucose control with GLP-1 receptor agonists has been associated with worsening of diabetic retinopathy; patients should have regular eye examinations and report any visual changes promptly.

Hypoglycaemia risk is low when incretin mimetics are used alone but increases when combined with insulin or sulfonylureas. These medicines are contraindicated in pregnancy and breastfeeding. Women of childbearing potential should use effective contraception during treatment, and those planning pregnancy should discuss stopping the medicine at least two months before conception (refer to the product SmPC for specific advice).

There have been reports of mood changes and suicidal ideation in patients taking GLP-1 receptor agonists, which are under ongoing review. Patients should seek medical advice if they experience new or worsening depression, anxiety, or thoughts of self-harm.

Patients should contact their GP if they experience persistent vomiting, signs of dehydration, severe abdominal pain, visual changes, or any symptoms causing significant concern. Suspected side effects can be reported via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or through the Yellow Card app.

NHS Availability and Prescribing Criteria

Access to incretin mimetics for weight management through the NHS is subject to strict eligibility criteria defined by NICE Technology Appraisals and must be provided within specialist weight management services. NICE guidance recommends that GLP-1 receptor agonists for weight management should only be offered as part of a specialist multidisciplinary tier 3 weight management service, not as a standalone intervention.

For semaglutide 2.4 mg (Wegovy), NICE recommends it as an option for weight management in adults within specialist weight management services, provided:

• BMI of 35 kg/m² or above (or 32.5 kg/m² or above for people from Black African, African-Caribbean, South Asian, Chinese, other Asian, or Middle Eastern family backgrounds, who are at equivalent risk at lower BMI thresholds), or

• BMI of 30–34.9 kg/m² (or 27.5–32.4 kg/m² for the ethnic groups above) and at least one weight-related comorbidity (such as hypertension, dyslipidaemia, obstructive sleep apnoea, or cardiovascular disease) and a high risk of cardiovascular disease

• The person has participated in a specialist weight management service

Treatment with semaglutide should be stopped if adequate weight loss (defined as at least 5% of initial body weight) has not been achieved after six months on the maintenance dose. NICE limits the use of semaglutide (Wegovy) on the NHS to a maximum of two years within specialist weight management services.

For liraglutide 3 mg (Saxenda), NICE recommends it as an option for weight management in adults within specialist weight management services, provided the person has a BMI of at least 35 kg/m² (or 32.5 kg/m² for certain ethnic groups as above) and has participated in a specialist weight management programme. Treatment should be stopped if at least 5% weight loss has not been achieved after 12 weeks on the maximum tolerated dose.

In practice, NHS availability varies by region due to capacity limitations within specialist services, supply constraints, and local commissioning decisions by Integrated Care Boards. Waiting lists for specialist weight management services can be substantial in some areas. Patients should discuss referral options with their GP.

Private prescribing remains an option for patients who meet clinical criteria but cannot access NHS treatment, though costs are substantial, typically ranging from £150–300 per month depending on the specific medicine and dose. Patients considering private treatment should ensure they receive appropriate medical assessment, monitoring, and support from qualified, UK-regulated healthcare professionals and obtain medicines only from registered UK pharmacies. Patients should be aware of the risk of counterfeit or illicitly supplied GLP-1 receptor agonist pens purchased online and should avoid unregulated sources.

Lifestyle Changes and Long-Term Weight Management

Incretin mimetics should never be viewed as a standalone solution for weight management but rather as an adjunct to comprehensive lifestyle modification. NICE guidance emphasises that these medicines are most effective when integrated into a multicomponent weight management programme that addresses diet, physical activity, and behavioural factors. Evidence consistently demonstrates that patients who combine medication with sustained lifestyle changes achieve superior and more durable weight loss outcomes.

Dietary modifications remain fundamental to successful weight management. Patients should work with a registered dietitian (regulated by the Health and Care Professions Council) or a Registered Nutritionist (regulated by the Association for Nutrition) to develop sustainable eating patterns that create an appropriate energy deficit whilst ensuring adequate nutrition. This typically involves:

• Adopting a balanced, portion-controlled diet rich in vegetables, fruits, whole grains, and lean proteins

• Reducing intake of processed foods, sugary beverages, and high-fat items

• Practising mindful eating and recognising hunger and satiety cues

• Planning meals and snacks to avoid impulsive food choices

Physical activity provides multiple benefits beyond energy expenditure, including improved cardiovascular health, enhanced insulin sensitivity, preservation of lean muscle mass during weight loss, and positive effects on mood and wellbeing. The UK Chief Medical Officers' Physical Activity Guidelines recommend at least 150 minutes of moderate-intensity aerobic activity weekly (or 75 minutes of vigorous-intensity activity), alongside muscle-strengthening activities on two or more days. Patients should start gradually and progressively increase activity levels according to their fitness and any physical limitations.

Behavioural strategies address the psychological and environmental factors that influence eating behaviours and activity patterns. Cognitive behavioural therapy techniques, goal-setting, self-monitoring, stress management, and addressing emotional eating can significantly enhance long-term success. Support from healthcare professionals, the NHS Digital Weight Management Programme, local tier 3 weight management services, peer groups, or other structured programmes provides accountability and encouragement.

Long-term maintenance represents the greatest challenge in weight management. Evidence from extension studies of GLP-1 receptor agonist trials shows that discontinuing these medicines typically results in weight regain, highlighting the chronic nature of obesity and the need for ongoing treatment strategies. Patients should be counselled that weight management is a lifelong commitment requiring sustained lifestyle modifications, with or without continued pharmacological support. Regular follow-up with healthcare professionals helps monitor progress, adjust treatment plans, address barriers, and provide ongoing motivation for maintaining healthy behaviours.

Frequently Asked Questions