Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

BMI ≥30 kg/m²; or else BMI ≥27 kg/m² with an obesity-related comorbidity

1st line – dietary changes

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ONGOING
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BMI ≥30 kg/m²; or else BMI ≥27 kg/m² with an obesity-related comorbidity
1st line – 

dietary changes

An intake of 1000-1200 kcal/day for women and 1200-1500 kcal/day for men should produce a caloric deficit of 500-1000 kcal/day.[1]

While some clinical trials have found small differences favouring low-carbohydrate and low-glycaemic index diets, no single diet has emerged as superior to the others over the long term (i.e., >1 year).[107][108][109][110]

Adherence to the diet (i.e., compliance) and the reliability of patient reporting of caloric intake have been problematic in studies on dietary intervention.

Plus – increase in physical activity

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ONGOING
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BMI ≥30 kg/m²; or else BMI ≥27 kg/m² with an obesity-related comorbidity
Plus – 

increase in physical activity

Treatment recommended for ALL patients in selected patient group

Meta-analyses have indicated that weight loss is greater in diet plus exercise regimens than in diet-only regimens; however, exercise regimens alone, without reduced-calorie diets, are not effective for weight loss.[102][112] In general, even light physical activity is beneficial compared with no activity. Adults should seek to decrease sedentary tasks as much as possible and gradually increase activity level to meet recommended weekly exercise targets.[92]

Examples of physical activities and their respective rate of caloric expenditure for a 100 kg patient are: walking at 3 miles per hour (350 kcal/hour); bicycling on level ground at 10-12 miles per hour (600 kcal/hour); jogging at 5 miles per hour (800 kcal/hour); swimming freestyle for 1 standard lap (1000 kcal/hour); running 7.5 miles per hour (1200 kcal/hour).

Consider – psychological therapy

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ONGOING
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BMI ≥30 kg/m²; or else BMI ≥27 kg/m² with an obesity-related comorbidity
Consider – 

psychological therapy

Additional treatment recommended for SOME patients in selected patient group

Recommended in all receptive patients as an effective adjunct to diet and exercise.[1] Psychological intervention appears to be most effective when it is in the form of behavioural or cognitive behavioural therapy.[117][118]

Web-based behavioural interventions, especially via interactive social media platforms, may provide useful adjunctive support and educational tools for the achievement and maintenance of weight loss, and the prevention of excessive weight gain.[121][122][127] Access to social media has led to the adoption of these web-based applications for exercise and dietary coaching for weight loss and management; however, not all apps are created equal, and overall, evidence into their efficacy for individual sustained weight loss is lacking.[124]​ In one review of 28 top-rated weight-loss applications, Noom was given the highest total score based on five independent ranking categories.[124]​ However, even with Noom, the overall efficacy of total and sustained weight loss was most correlated with frequent and sustained engagement by each individual user.[125]​ Despite their initial promise, further research is still needed to determine their long-term effectiveness.​

Therapy also seems to be best when given in person by a therapist compared with self-directed therapy.[119]

The practice of frequent self-weighing seems to have a beneficial effect on weight loss.[120]

Consider – pharmacotherapy

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ONGOING
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BMI ≥30 kg/m²; or else BMI ≥27 kg/m² with an obesity-related comorbidity
Consider – 

pharmacotherapy

Additional treatment recommended for SOME patients in selected patient group

​In the US, adding medicine is recommended as an adjunct to diet and exercise in people whose BMI is ≥30 kg/m², or >27 kg/m² if associated with obesity-related comorbidity.[1][98]​​​[128]​​​​

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist targeting areas of the brain that regulate appetite and food intake.[129]​ It is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI ≥30 kg/m², or ≥27 kg/m², in the presence of at least one weight-related comorbidity.[130]​ In the UK, the National Institute for Health and Care Excellence (NICE) recommends the use of semaglutide in adults as an adjunct to lifestyle measures only when it is used for a maximum of 2 years, within a specialist weight management service, and in patients who have at least 1 weight-related comorbidity and have BMI ≥35 kg/m² (or a BMI between 30 kg/m² to <35 kg/m² who meet the criteria for referral to specialist weight management services).[131] NICE recommends using lower BMI thresholds (usually reduced by 2.5 kg/m²) for people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean family backgrounds. Randomised controlled trial (RCT) data showed that patients receiving semaglutide lost an average of 6% to 16% of their total body weight compared with controls, when combined with other behavioural modifications.[132][133]​​​ Semaglutide has also demonstrated cardiovascular benefits; RCT data showed that in adults aged 45 and older with overweight or obesity who have concurrent cardiovascular disease (but no history of diabetes), semaglutide reduces the overall risk of major cardiac events (heart attack, stroke, or cardiovascular death) by 20% at a mean follow-up of 40 months.[134]​ Based on these results, the Food and Drug Administration (FDA) has expanded its indication, granting approval for the use of semaglutide to reduce the risk of major cardiac events in adults with cardiovascular disease and either obesity or overweight. Common adverse effects include gastrointestinal disturbance, headache, fatigue, and hypoglycaemia in diabetic patients. Some evidence suggests that overall weight loss with semaglutide may include both a reduction in adiposity as well as a reduction in fat-free mass (a surrogate marker for muscle mass); however, the long-term implications of this are currently unclear.[135]​ Semaglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma and patients with multiple endocrine neoplasia syndrome type 2 due to an increased risk of medullary thyroid cancer.

Liraglutide is another GLP-1 receptor agonist. In the UK, NICE recommends liraglutide as an option only for adults with a BMI ≥35 kg/m² (or ≥32.5 kg/m² for members of ethnic groups known to be at greater risk), non-diabetic hyperglycaemia, a high risk of cardiovascular disease, and if prescribed by a specialist weight management service.[136]​ RCTs of liraglutide have been conducted as part of the Satiety and Clinical Adiposity-Liraglutide Evidence in Nondiabetic and Diabetic Individuals (SCALE) programme.[141] The contraindications and warnings and safety profile of liraglutide is similar to that of semaglutide.[130] In one trial comparing use of semaglutide or liraglutide in addition to behavioural modifications, patients receiving semaglutide had significantly greater weight loss.[142]

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist that is also administered as a weekly subcutaneous injection. It is approved for the same indications as semaglutide. RCT evidence suggests that, when combined with intensive lifestyle modifications, patients receiving a weekly dose of tirzepatide achieved weight loss of around 18% of their total body weight.[143][144] In another RCT, patients who received tirzepatide experienced an average weight reduction of 20.9%.[145]​ A dose-dependent reduction in weight was demonstrated in both studies.[143][145]​ Tirzepatide has the same contraindications and warnings, and a similar adverse effect profile to other GLP-1 receptor agonists.[146]​ Note that tirzepatide should not be used concurrently with a GLP-1 receptor agonist.​​

Orlistat is an oral inhibitor of fat absorption (inhibitor of gastric and pancreatic lipases). It has been shown to have modest effectiveness (about 5% loss in body weight) when combined with diet and exercise alone, but mild gastrointestinal side effects (including diarrhoea) are common.[147] American Gastroenterological Association (AGA) guidelines recommend against the use of orlistat, but note that it may be reasonable if the patient values modest weight loss over possible gastrointestinal adverse events.[128]​ Combining orlistat with L-carnitine may offer better results than orlistat as a monotherapy.[148]​ Patients who use orlistat should take a multivitamin containing fat-soluble vitamins at least 2 hours before or after orlistat.[128]

Two oral combination therapies, naltrexone/bupropion and phentermine/topiramate, are available. Naltrexone/bupropion should be avoided in patients with seizure disorders or substance misuse issues. Both naltrexone/bupropion and phentermine/topiramate should be used with caution and at lower doses in patients with hepatic or renal impairment. Phentermine/topiramate may not be suitable for those with hypertension or arrhythmias due to the adrenergic effects of phentermine. Topiramate is associated with congenital malformations; women of childbearing potential should be counselled on effective contraception.[128] Phentermine is a controlled substance due to its abuse potential, and should not be prescribed for patients with a history of substance misuse disorders.

Setmelanotide is a melanocortin 4 (MC4) receptor agonist that is approved for certain rare genetic conditions that can cause obesity at an early age.[158][159]​ Patients with confirmed genetic testing for pro-opiomelanocortin (POMC), proprotein subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency are candidates for setmelanotide.[158] Common side effects include gastrointestinal disturbances, headache, injection-site reactions, and skin hyperpigmentation.[158]

Choice of pharmacotherapy is heavily dependent on multiple variables, including presence of comorbidities, genetic conditions, and route of administration.

Semaglutide and liraglutide (both subcutaneous) are first-line pharmacological options with clinically proven weight loss and cardiometabolic effects, provided there are no contraindications. They are both approved for long-term use. Setmelanotide is a first-line option for patients with POMC, PCSK1, or LEPR deficiency. Setmelanotide is also approved for the treatment of obesity and hunger control in patients with confirmed Bardet-Biedl syndrome.[161]

If semaglutide or liraglutide are contraindicated or not tolerated, second-line options include naltrexone/bupropion and phentermine/topiramate. These options may also be beneficial in patients with certain comorbidities. For example, in patients with obesity who also suffer migraine headaches, phentermine/topiramate may be considered as topiramate also treats migraines. Naltrexone/bupropion may be considered in patients with obesity who also desire pharmacological aid in smoking cessation, or in patients with depression.[128]​ If first- or second-line options are not tolerated, a third-line option is orlistat if the patient values modest weight loss over the possible gastrointestinal side effects of this drug.[128]​ All are approved for long-term use.

Phentermine monotherapy is approved for short-term use only, and is therefore a third-line treatment option.

Primary options

semaglutide: 0.25 mg subcutaneously once weekly for 4 weeks initially, increase dose gradually according to response and tolerance every 4 weeks, maximum 2.4 mg once weekly

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OR

liraglutide: 0.6 mg subcutaneously once daily initially, increase dose gradually according to response and tolerance at weekly intervals, maximum 3 mg/day

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OR

tirzepatide: 2.5 mg subcutaneously once weekly for 4 weeks initially, increase dose gradually according to response and tolerance every 4 weeks, maximum 15 mg once weekly

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OR

setmelanotide: 2 mg subcutaneously once daily for 2 weeks initially, titrate dose gradually according to response and tolerance, maximum 3 mg/day

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Secondary options

naltrexone/bupropion hydrochloride: 8 mg (naltrexone)/90 mg (bupropion) orally (extended-release) once daily in the morning for 1 week, followed by 8/90 mg twice daily for 1 week, followed by 16/180 mg in the morning and 8/90 mg in the evening for 1 week, then 16/180 mg twice daily thereafter

OR

phentermine hydrochloride/topiramate: 3.75 mg (phentermine)/23 mg (topiramate) orally (extended-release) once daily in the morning initially for 14 days, increase gradually according to response, maximum 15 mg (phentermine)/92 mg (topiramate) per day

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Tertiary options

orlistat: 120 mg orally three times daily with fat-containing meals

OR

phentermine: 15 to 37.5 mg orally once daily for up to 4 weeks

Consider – surgical therapy

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ONGOING
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BMI ≥30 kg/m²; or else BMI ≥27 kg/m² with an obesity-related comorbidity
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BMI 30-34.9 kg/m² and type 2 diabetes or weight loss and comorbidity improvement not achieved with nonsurgical management
Consider – 

surgical therapy

Additional treatment recommended for SOME patients in selected patient group

The American Society for Metabolic and Bariatric Surgery and International Federation for the Surgery of Obesity and Metabolic Disorders recommend bariatric surgery for patients with a BMI 30-34.9 kg/m² (class I obesity) who do not achieve substantial durable weight loss or comorbidity improvement with nonsurgical management, and patients with a BMI ≥30 kg/m² and type 2 diabetes mellitus.[173]​ BMI thresholds do not apply equally to all populations, so bariatric surgery may also be considered for some individuals with lower BMI (e.g., in Asian populations, clinical obesity is defined as BMI >25 kg/m²).[173]​ There is no upper age limit for bariatric surgery, but patients should be carefully assessed for comorbidities and frailty.[173]​

Gastric procedures attempt to limit the size of the gastric reservoir, while small bowel procedures bypass various lengths of the intestine. Surgery works by reducing hunger and increasing fullness.

Contraindications in all of the available surgical procedures include unstable coronary artery disease, advanced liver disease with portal hypertension, cognitive impairment precluding informed consent, inflammatory bowel disease, extensive intra-abdominal adhesion, and cancer.

Roux-en-Y gastric bypass may be more efficacious than gastric banding, but the latter may have less morbidity.[177][178][179]

Laparoscopic sleeve gastrectomy has become the most commonly performed surgical treatment for obesity, primarily due to good short-term results. Sleeve gastrectomy produces more weight loss than the adjustable gastric band, but less than the gastric bypass.[181]

Limited preliminary data have suggested that the intragastric balloon, in conjunction with dieting, may have short-term efficacy in weight loss.[186][187][188] Intragastric balloons were initially associated with several devastating adverse events, causing removal from the US market.[189]​ However, newer models with filling mediums that include water and air have since been approved by the Food and Drug Administration and are being studied.[188]

BMI ≥35 kg/m² with or without comorbidities

1st line – surgical therapy

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ONGOING
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BMI ≥35 kg/m² with or without comorbidities
1st line – 

surgical therapy

According to a National Institutes of Health consensus statement from 1991, patients with a BMI ≥40 kg/m² (i.e., class III obesity), or ≥35 kg/m² with obesity-related comorbidity (e.g., hypertension, diabetes, sleep apnoea, GORD) may be candidates for most bariatric procedures.[1][167]​​[171][172]​​​ However, these guidelines are now over 30 years old. The increased use of minimally invasive (i.e., laparoscopic) approaches to bariatric procedures has significantly decreased the morbidity and mortality associated with these operations. This has contributed to an overall broadening of bariatric indications. As of 2022, the American Society for Metabolic and Bariatric Surgery and the International Federation for the Surgery of Obesity and Metabolic Disorders recommend bariatric surgery for patients with a BMI ≥35 kg/m² with or without comorbidities.[173]​ 

There is no upper age limit for bariatric surgery, but patients should be carefully assessed for comorbidities and frailty.[173]

Gastric procedures attempt to limit the size of the gastric reservoir, while small bowel procedures bypass various lengths of the intestine. Surgery works by reducing hunger and increasing fullness.

Contraindications in all of the available surgical procedures include unstable coronary artery disease, advanced liver disease with portal hypertension, cognitive impairment precluding informed consent, inflammatory bowel disease, extensive intra-abdominal adhesion, and cancer.

Roux-en-Y gastric bypass may be more efficacious than gastric banding, but the latter may have less morbidity.[177][178][179]

Laparoscopic sleeve gastrectomy has become the most commonly performed surgical treatment for obesity, primarily due to good short-term results. Sleeve gastrectomy produces more weight loss than the adjustable gastric band, but less than the gastric bypass.[181]

Limited preliminary data have suggested that the intragastric balloon, in conjunction with dieting, may have short-term efficacy in weight loss.[186][187][188]​​ Intragastric balloons were initially associated with several devastating adverse events, causing removal from the US market.[189]​ However, newer models with filling mediums that include water and air have since been approved by the FDA and are being studied.[188]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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