Saxenda (liraglutide 3.0 mg) is a prescription-only injectable medicine licensed in the UK for weight management in adults with obesity or overweight, and in adolescents aged 12–17 years with obesity. Understanding how Saxenda works is essential for patients and clinicians considering this treatment option. Saxenda belongs to a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists, which mimic a natural gut hormone that regulates appetite and food intake. By activating GLP-1 receptors in the brain and digestive system, Saxenda reduces hunger, increases feelings of fullness, and supports calorie reduction when used alongside diet, exercise, and behavioural support.

What Is Saxenda and How Does It Work?

Saxenda (liraglutide 3.0 mg) is a prescription-only injectable medicine licensed in the UK for weight management in adults with obesity or overweight alongside diet and exercise. It is also licensed for adolescents aged 12-17 years with obesity and body weight above 60 kg, under specialist supervision. Saxenda belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists, originally developed for type 2 diabetes management but now used at higher doses for chronic weight management.

Saxenda works by mimicking the action of a naturally occurring hormone called GLP-1, which is released by the intestines after eating. This hormone plays a crucial role in regulating appetite, food intake, and blood glucose levels. By activating GLP-1 receptors in the brain and digestive system, Saxenda helps individuals feel fuller for longer, reduces hunger between meals, and supports a reduction in overall calorie intake.

The medication is administered once daily via subcutaneous injection, typically into the abdomen, thigh, or upper arm. Treatment is initiated at a low dose (0.6 mg daily) and gradually increased over five weeks to the maintenance dose of 3.0 mg daily. This titration schedule helps minimise gastrointestinal side effects, which are common during the initial weeks of therapy.

It is important to understand that Saxenda is not a standalone solution for weight loss. The Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Health and Care Excellence (NICE) emphasise that liraglutide should be used as part of a comprehensive weight management programme that includes dietary modification, increased physical activity, and behavioural support.

In the NHS, NICE guidance (TA664) restricts Saxenda to adults who meet specific criteria and are referred to specialist tier 3 or 4 weight management services. Treatment is typically limited to a maximum of two years, with a requirement to demonstrate at least 5% weight loss after 12 weeks at the maintenance dose to continue treatment. Saxenda should not be used alongside other GLP-1 receptor agonists, DPP-4 inhibitors, or other weight-loss medications.

The Mechanism of Action: GLP-1 Receptor Agonism

The therapeutic effect of Saxenda is mediated through its action as a GLP-1 receptor agonist. Liraglutide is a synthetic analogue of human GLP-1, sharing 97% structural similarity with the endogenous hormone. However, unlike natural GLP-1, which is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) within minutes, liraglutide has been modified to resist enzymatic breakdown, resulting in a half-life of approximately 13 hours. This extended duration of action allows for once-daily dosing and sustained therapeutic effects.

When administered, liraglutide binds to and activates GLP-1 receptors located throughout the body, particularly in key areas involved in appetite regulation and metabolic control. These receptors are found in the pancreas, gastrointestinal tract, and importantly, in specific regions of the brain including the hypothalamus and brainstem. The hypothalamus serves as the body's primary appetite control centre, integrating signals about energy balance and nutritional status.

Activation of GLP-1 receptors in the brain triggers a cascade of neurological signals that reduce appetite and increase feelings of satiety. Research suggests that liraglutide acts on the arcuate nucleus and paraventricular nucleus within the hypothalamus, areas rich in neurons that regulate feeding behaviour. By modulating the activity of these appetite-regulating centres, Saxenda helps individuals experience reduced hunger and enhanced satisfaction after meals.

Additionally, some evidence suggests GLP-1 receptor activation may influence the reward pathways in the brain, potentially reducing cravings for high-calorie, palatable foods, though this research is still emerging from small human studies and preclinical work. This multi-level action on both homeostatic (energy balance) and potentially hedonic (reward-driven) eating behaviours may contribute to the medication's effectiveness in supporting weight loss when combined with lifestyle interventions.

Effects on Appetite, Satiety and Food Intake

One of the primary mechanisms through which Saxenda facilitates weight loss is by modulating appetite and satiety signals. Clinical studies have demonstrated that patients treated with liraglutide 3.0 mg report significantly reduced hunger, increased fullness after meals, and decreased preoccupation with food compared to placebo.

The appetite-suppressing effects of Saxenda occur through several pathways. Firstly, by activating GLP-1 receptors in the hypothalamus, the medication appears to influence the production and release of neuropeptides involved in hunger control. This neurochemical shift helps individuals feel satisfied with smaller portion sizes and experience less frequent hunger between meals.

Secondly, Saxenda enhances postprandial satiety—the feeling of fullness that follows eating. Patients often report that they feel satisfied sooner during meals and that this sensation of fullness persists for longer periods. This effect is particularly valuable for individuals who have previously struggled with portion control or frequent snacking. By naturally reducing the desire to eat, Saxenda supports adherence to a reduced-calorie diet without the intense hunger that often undermines weight loss efforts.

Clinical trial data indicate that treatment with Saxenda is associated with a significant reduction in energy intake. Studies from the SCALE programme show that patients using liraglutide 3.0 mg typically consume fewer calories per day compared to baseline. This caloric deficit, sustained over weeks and months, contributes significantly to progressive weight loss. It is worth noting that the appetite-regulating effects typically become apparent within the first few weeks of treatment, though optimal weight loss outcomes generally require several months of consistent use alongside dietary and lifestyle modifications.

Impact on Gastric Emptying and Blood Glucose

Beyond its central effects on appetite, Saxenda also exerts important actions on the gastrointestinal system that contribute to weight management. One of the key peripheral mechanisms is the slowing of gastric emptying—the rate at which food moves from the stomach into the small intestine. By activating GLP-1 receptors in the stomach and gastrointestinal tract, liraglutide delays gastric emptying, which prolongs the sensation of fullness after eating and helps regulate the rate of nutrient absorption.

This delayed gastric emptying has several beneficial effects. It contributes to enhanced satiety by maintaining stomach distension for longer periods, sending continued signals to the brain that food is still being processed. Additionally, the slower release of nutrients into the bloodstream helps prevent rapid spikes in blood glucose levels following meals, which can be particularly advantageous for individuals with prediabetes or insulin resistance. It's important to note that this effect on gastric emptying may attenuate somewhat with long-term use.

Saxenda also influences glucose homeostasis through its effects on pancreatic function. In the presence of elevated blood glucose, liraglutide stimulates insulin secretion from pancreatic beta cells whilst simultaneously suppressing the release of glucagon from alpha cells. Glucagon is a hormone that raises blood glucose by promoting glucose production in the liver. By reducing glucagon secretion, Saxenda helps prevent excessive glucose output, contributing to improved glycaemic control. However, it's important to emphasise that Saxenda is licensed for weight management, not for glycaemic control or diabetes treatment.

It is important to note that these glucose-lowering effects are glucose-dependent, meaning they occur primarily when blood sugar levels are elevated. This mechanism significantly reduces the risk of hypoglycaemia (dangerously low blood sugar) compared to some other diabetes medications. However, patients using Saxenda alongside other glucose-lowering therapies, particularly insulin or sulphonylureas, should have their doses of these medications reduced and blood glucose levels carefully monitored to prevent hypoglycaemia, as advised in the Saxenda SmPC.

The delayed gastric emptying may affect the absorption of some oral medicines. Additionally, patients taking warfarin or other coumarins should have their INR monitored when initiating Saxenda treatment, as changes in absorption may affect anticoagulation.

Clinical Evidence: Weight Loss Outcomes and Efficacy

The efficacy of Saxenda for weight management has been extensively evaluated in the SCALE (Satiety and Clinical Adiposity – Liraglutide Evidence) clinical trial programme, which included over 5,000 participants across multiple international studies. These randomised, double-blind, placebo-controlled trials provide robust evidence for the medication's effectiveness when used alongside lifestyle interventions.

In the pivotal SCALE Obesity and Prediabetes trial, adults with obesity or overweight (with at least one weight-related comorbidity) were randomised to receive either liraglutide 3.0 mg or placebo, both combined with a reduced-calorie diet and increased physical activity. After 56 weeks of treatment, participants receiving Saxenda achieved an average weight loss of 8.4 kg (approximately 8% of initial body weight), compared to 2.8 kg (2.6%) in the placebo group. Notably, 63.2% of patients on Saxenda lost at least 5% of their body weight—a threshold considered clinically meaningful—compared to 27.1% in the placebo group.

Furthermore, approximately one-third of Saxenda-treated patients achieved weight loss exceeding 10% of their initial body weight, which is associated with significant improvements in obesity-related health conditions. These benefits included reductions in waist circumference, improvements in blood pressure, and favourable changes in lipid profiles and markers of cardiovascular risk.

The SCALE Obesity and Prediabetes 160-week extension study demonstrated that weight loss could be sustained for up to three years with continued treatment, though weight regain typically occurs following discontinuation, highlighting the chronic nature of obesity management.

In the UK, NICE guidance (TA664) recommends that treatment with Saxenda should be discontinued if patients do not achieve at least 5% weight loss after 12 weeks at the maintenance dose, as continued use is unlikely to provide meaningful benefit. This stopping rule ensures appropriate use of the medication and helps identify patients who may require alternative weight management strategies.

NICE restricts NHS-funded treatment to adults who meet specific BMI criteria, have pre-diabetes or a high risk of cardiovascular disease, and are referred to specialist tier 3 or 4 weight management services. Treatment is typically limited to a maximum of two years.

Who Can Use Saxenda and Important Safety Considerations

Saxenda is licensed in the UK for adults with a body mass index (BMI) of 30 kg/m² or greater (obesity), or a BMI of 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbidity such as type 2 diabetes, hypertension, dyslipidaemia, or obstructive sleep apnoea. It is also licensed for adolescents aged 12-17 years with obesity (BMI corresponding to ≥30 kg/m² in adults) and body weight above 60 kg, under specialist supervision.

On the NHS, NICE guidance (TA664) restricts Saxenda to adults who meet specific criteria and are referred to specialist tier 3 or 4 weight management services. The medication must be prescribed as part of a comprehensive weight management programme that includes dietary modification and increased physical activity.

Important contraindications include pregnancy and breastfeeding, as the safety of liraglutide has not been established in these populations. Women of childbearing potential should use effective contraception during treatment.

Saxenda should not be used in combination with other GLP-1 receptor agonists, DPP-4 inhibitors, or other weight-loss medications.

Patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 should be counselled about the potential risk identified in animal studies (though there is no confirmed link in humans). Patients should be advised to report symptoms such as a neck mass, dysphonia, dysphagia, or persistent dyspnoea.

The most common adverse effects are gastrointestinal symptoms, including nausea, vomiting, diarrhoea, and constipation, which typically occur during dose escalation and often diminish over time. Patients should be advised that these effects are usually temporary and can be minimised by following the gradual dose titration schedule and avoiding large, high-fat meals.

Serious but rare adverse effects include pancreatitis (inflammation of the pancreas), gallbladder disease, and increased heart rate. If pancreatitis is suspected, Saxenda should be discontinued immediately and not restarted if pancreatitis is confirmed. Patients should be counselled to seek immediate medical attention if they experience severe, persistent abdominal pain, which may indicate pancreatitis.

Persistent or severe vomiting and diarrhoea can lead to dehydration and acute kidney injury; patients should maintain adequate fluid intake and seek medical advice if these symptoms persist. Rarely, serious hypersensitivity reactions including anaphylaxis and angioedema may occur, requiring immediate medical attention.

Additionally, individuals with a history of depression or suicidal ideation should be monitored carefully, as mood changes have been reported in some patients.

Patients should contact their healthcare provider if they experience persistent vomiting or diarrhoea, signs of gallbladder problems (such as jaundice or severe upper abdominal pain), or symptoms of hypoglycaemia if taking concurrent diabetes medications. Regular follow-up with healthcare professionals is essential to monitor treatment response, manage side effects, and provide ongoing support for lifestyle modifications that are crucial to long-term weight management success.

Suspected adverse reactions should be reported via the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk).

Frequently Asked Questions