The World Health Organization reported in April 2020 that in 2016 more than 1.9 billion adults worldwide were overweight and of these 650 million people were obese.1 In the UK, obesity prevalence increased steeply between 1993 and 2000 and, by 2018, 63% of adults in England were overweight or obese and the proportion of adults who were obese was 28%.2 In the United States, the age standardised prevalence of obesity in adults is nearly 40%3 whereas in countries like Japan and Korea obesity levels are less than 10%.2 Obesity increases the risk of hypertension, type 2 diabetes, atherosclerosis and cardiovascular disease.4 Moreover, it is also associated with higher risk for gastro-oesophageal reflux disease, gallstones, cancer, obstructive sleep apnoea and reduced quality of life.5-8 In a clinical setting, body mass index (BMI) is an internationally accepted measure of adiposity in adults. BMI correlates with the amount of body fat, but it does not directly measure body fat9 and the values are age independent and the same for both sexes. As per BMI, the degree of overweight or obesity is classified as: Healthy weight – 18.5–24.9kg/m2; Overweight – 25–29.9kg/m2; Obesity I – 30–34.9kg/m2; Obesity II – 35–39.9kg/m2; and Obesity III – ≥40kg/m2.5 The American Association of Clinical Endocrinology recommends that individuals with BMI ≥25kg/m2 (or ≥23kg/m2 in South Asian, Southeast Asian, and East Asian adults) should be screened annually for presence of obesity and its related complications.10 The health benefits of weight loss for patients diagnosed with obesity and its related complications are immense. Several clinical practice guidelines have been published and most of them recognise and recommend the importance of diet, exercise and behavioural modifications to be the cornerstone of treatment for obesity.5, 9-13 Pharmacological interventions are to be considered as an adjunctive therapy in individuals with BMI ≥27kg/m2 with related complications and if BMI ≥30kg/m2 without any comorbid conditions.10, 14 Bariatric surgery is recommended for people with BMI ≥40kg/m2 or between 35–40kg/m2 and severe complications which can be improved with weight loss or when other weight loss strategies have failed.5 Very few and effective drugs are currently available for the treatment of obesity. Medications that are currently approved include phentermine, topiramate/phentermine, lorcaserin, orlistat, naltrexone/bupropion and liraglutide. Each medication has distinctive qualities regarding efficacy, adverse effects, dose requirements and drug interactions. Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist with 97% structural homology to endogenous human GLP-1. Native GLP-1 has a short elimination half-life of 1–2 minutes, whereas liraglutide has a long half-life of about 13 hours and can be administered once daily by subcutaneous injection.15 Liraglutide enhances glucose dependent stimulation of pancreatic insulin secretion and inhibition of glucagon secretion.16 It also delays gastric emptying and increases satiety by central effects on the hypothalamus.16 The weight loss is a dose dependent effect and is principally due to suppression of appetite and direct effects on gastric emptying which causes early satiety. Liraglutide was initially approved on 30 June 2009 by the European Medicines Agency (EMA) and on 25 January 2010 by the Food and Drug Administration (FDA), at a maximum dose of 1.8mg daily subcutaneously for the management of type 2 diabetes. It also gained approval from the FDA (on 23 December 2014) and EMA (on 23 January 2015) for weight reduction (at a maximum dose of 3.0mg daily, subcutaneously combined with lifestyle modification) in obese individuals or people who are overweight with BMI of ≥27kg/m2 and have experienced at least one weight associated condition (prediabetes, dyslipidaemia, hypertension and sleep apnoea).17 In the UK, the National Institute for Health and Care Excellence (NICE) has issued its final appraisal document (GID-TA 10388; October 2020) for the use of liraglutide for managing overweight and obesity and the guidance published in December 2020.18 NICE recommended that liraglutide (Saxenda, Novo Nordisk) can be used alongside reduced calorie diet and increased physical activity in adults if they have a BMI of at least 35kg/m2 (adjustment in BMI thresholds for minority ethnic groups) and have non-diabetic hyperglycaemia (defined as HbA1c level of 42–47mmol/mol [6.0–6.4%] or a fasting glucose level of 5.5–6.9 mmol/L). These adults should also have a high risk of cardiovascular disease (CVD) based on risk factors such as hypertension and dyslipidaemia. NICE also suggested that liraglutide for weight management should be prescribed in secondary care by a specialist multidisciplinary tier 3 weight management service.18 Although the marketing authorisation for liraglutide (Saxenda) for weight management has been approved for patients with initial BMI of ≥30kg/m2 or ≥27kg/m2 to <30kg/m2 in the presence of at least one weight related comorbidity in other countries, NICE didn't recommend for its use in the full population covered by the marketing authorisation as evidence provided by the company (Novo Nordisk) was only for people with BMI ≥35kg/m2 with prediabetes and high risk for CVD.18 The Scottish Medicines Consortium (SMC) has not recommended the use of liraglutide for the management of obesity in NHS Scotland as yet. Liraglutide has been studied in several clinical trials evaluating its effectiveness, tolerability, and safety in overweight and obese individuals. (Appendix 1 available online at https://wchh.onlinelibrary.wiley.com/journal/20472900 provides a summary of the findings from selected and recent clinical trials). The earliest of these trials was a 20-week phase 319 dose ranging trial with an 84-week open label extension and change in body weight as a primary endpoint. All patients receiving liraglutide had significant weight loss compared with placebo (liraglutide 1.2mg vs placebo: p=0.003; and for all other doses vs placebo: p<0.0001). Weight loss was highest in patients with higher dose of liraglutide in comparison to orlistat (liraglutide 2.4mg vs orlistat: p=0.003; and liraglutide 3.0mg vs orlistat: p<0.0001). At least 76% of patients receiving liraglutide 3.0mg attained a 5% or higher weight loss compared to 30% in the placebo arm and 44% in the orlistat group. Two-year extension data were also published for this trial (n=398). Liraglutide 3.0mg showed a placebo corrected mean weight loss of 5.8kg at the end of the first year with reduction in prevalence of prediabetes and metabolic syndrome (p<0.01 for both).20 Dietary deficit of 500kcal/day and increased physical activity Liraglutide 1.2mg (-4.8kg), 1.8mg (-5.5kg), 2.4mg (-6.3kg), 3.0mg (-7.2kg) vs -2.8kg for placebo; p<0.01 for all Liraglutide 2.4mg (-6.3kg), 3.0mg (-7.2kg) vs -4.1kg for orlistat; p<0.01 for all Only patients with prediabetes completed 160 weeks of treatment Dietary deficit of 500kcal/day with physical activity of ≥150min/week. Liraglutide 3.0mg (-6.5kg) vs placebo (-2.0); p<0.0001. Risk of type 2 diabetes: 79% reduced risk with liraglutide; 3% of patients in liraglutide and 11% of patients in placebo group developed diabetes Medical arm: Arm 1: Low calorie diet (LCD) + intensive physical exercise (IPE); (n=25) Arm 2: LCD + IPE + liraglutide 3.0mg (n=25) Arm 3: Free diet + no suggestion of exercise Surgical arm: Sleeve gastrectomy (SG) (n=25) Arms 1 and 2: 1 month – Very LCD (813kcal/day) 11 month – LCD (12kcal/kg) Surgical arm (after surgery): 1 month – VLCD 11 month – Free diet. Physical exercise – 30min/day brisk walking + 3hr/week of aerobic exercise LCD + IPE = -15.4kg LCD + IPE + liraglutide 3.0mg = -26.2kg SG = -43.4kg LCD + IPE vs LCD + IPE + liraglutide = p<0.001 Four large phase 3 clinical trials were conducted under the acronym SCALE (Satiety and Clinical Adiposity – Liraglutide Evidence in non-diabetic and diabetic individuals). In the SCALE Obesity and Prediabetes trial,21 after 56 weeks, the difference in weight loss between liraglutide 3.0mg and placebo was -5.6kg (p<0.001) with a greater proportion of people having ≥5% (63.2% vs 27.1%; p<0.001) and ≥10% (33.1% vs 10.6%; p<0.001) weight loss in the liraglutide group. The SCALE Diabetes trial22 involved 846 adults with type 2 diabetes controlled by diet and exercise alone or in combination with up to three oral hypoglycaemic agents. After 56 weeks, liraglutide caused greater weight loss compared to placebo (-6.4kg vs -2.2kg; p<0.001) and also led to a greater proportion of patients who achieved ≥5% (54.3% vs 21.4%) and ≥10% (25.2% vs 6.7%) weight loss. In the SCALE Sleep Apnoea trial,23 at the end of 32 weeks, the liraglutide group demonstrated greater mean percentage body weight loss compared with placebo (-5.7% vs -1.6%) with a between group difference of -4.15%. Finally, in the SCALE Maintenance trial,24 patients in the liraglutide group attained a weight loss of 6.0±0.9% in the run-in period and an additional 6.2±7.3% on average after the run-in period compared to 0.2±7.0% average weight loss with placebo. A total of 81.4% patients who received liraglutide were able to maintain ≥5% weight loss from the run-in period compared to 48.9% (p<0.0001) in the placebo group and 50% of patients in the liraglutide group also lost an additional ≥5% of weight after the run-in period compared with 21.8% (p<0.0001) in the placebo group. The three-year extension of the SCALE Obesity and Prediabetes trial25 evaluated the effect of liraglutide 3.0mg on weight loss, safety and time of onset of type 2 diabetes in individuals with prediabetes. After 160 weeks, the liraglutide group lost a greater percentage of body weight (-6.1% vs -1.9%; p<0.0001) and the proportion of patients who lost ≥5% (49.6% vs 23.7%), >10% (24.8% vs 9.9%) and >15% (11% vs 3.1%) of body weight compared to placebo was also higher. The time to onset of type 2 diabetes was 2.7 times longer with liraglutide than with placebo (95% CI 1.9–3.9; p<0.0001) corresponding with a hazard ratio of 0.21 (95% CI 0.13–0.34). A more recent non-randomised trial26 compared the effects of intensive lifestyle modification with or without liraglutide 3.0mg daily with sleeve gastrectomy in obese individuals. Patients in the liraglutide arm showed greater change in absolute percentage of body weight at one year (-23.6% vs -14.1%; p<0.001) with similar reduction in lean body mass (-15.2% vs -9.4%; p=0.03) and fat mass (-28.4% vs -20.7%; p=0.06) in comparison to patients with intensive lifestyle modifications alone.26 Similarly, in a trial in adolescents with obesity, liraglutide 3.0mg was found to be superior to placebo with regard to the change from baseline in the BMI standard deviation score at week 56 (estimated difference -0.22; 95% CI -0.37 to -0.08; p=0.002). A reduction in BMI of at least 5% was observed more in the liraglutide group (estimated percentage 43.3% vs 18.7%) in comparison to placebo.27 The real world clinical effectiveness of liraglutide 3.0mg in combination with diet and exercise has been reported in a Canadian cohort. In 311 individuals after ≥ four months of therapy, weight loss was -7.0kg (p<0.001) and -8.0kg (p<0.001) after ≥ six months. Percentage change in body weight was 7.1% in the ≥ six-month group and 6.3% in the ≥ four-month group. Moreover, in the ≥ six-month group, 64.1% and 34.5% lost ≥5% and >10% body weight, respectively.28 Similar reports were also obtained from an Italian cohort of 93 non-diabetic obese and overweight individuals. Sixty patients who reached the final dose of liraglutide 3.0mg lost 7.1% of weight and 68.3%, 20.0% and 10% lost ≥5%, 10% and 15% of body weight, respectively.29 Finally, in a Spanish observational cohort study, liraglutide 3.0mg demonstrated greater weight loss than orlistat (-7.7kg vs -3.3kg) and more individuals lost at least 5% of their baseline weight with liraglutide (64.7%) in comparison to orlistat (27.4%).30 Obesity is a chronic and complex condition and there is no ‘quick fix’ or ‘magic bullet’ to reduce body weight and its associated complications. Liraglutide provides a new and attractive option for weight management in combination with reduced-calorie diet and increased physical activity. The clinical and real world data have shown that liraglutide 3.0mg is superior to placebo and orlistat in weight reduction and improvements in obesity related conditions. Patients who may particularly benefit from liraglutide are those who have failed to improve with other weight loss measures (diet, exercise and other drugs) or those who have prediabetes. Further studies are needed in large and diverse populations with varying race/ethnicities to establish the long-term effectiveness of liraglutide, as currently the appropriate duration for which patients need treatment is not well established. In most clinical trials, gastrointestinal adverse effects were observed among participants receiving liraglutide, therefore initiation, maintenance and dose titration should be carefully supervised at frequent intervals and added caution should be utilised in patients with a previous history of gastroparesis, pancreatitis and renal impairment. Liraglutide is expensive but NICE has found it to be a cost-effective use of NHS resources and therefore clinicians should be proactive in using the drug for the management of obesity in appropriate patients. There are no conflicts of interest declared.