Approach

​Diet and exercise is the initial approach for the obese patient who wishes to lose weight.[1][101] [ Cochrane Clinical Answers logo ] ​​ A combination of a reduced-calorie diet and exercise is more efficacious than either alone.[102] Additional weight loss may be possible with some medicine regimens.[102] The initial goal of weight loss therapy (diet and exercise) is a 10% reduction in body weight over a 6-month period.[1] This equates to a loss of 0.23 to 0.454 kg per week in the patient with a BMI of ≤35 kg/m², and 0.454 to 0.91 kg per week in the patient with a BMI of >35 kg/m². After the initial 6-month period, the patient is re-assessed to determine the efficacy of the therapy, whether the patient needs to lose more weight, or whether a weight-maintenance programme may be established.​​

Dietary changes

For weight reduction, 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] The main focus of dieting has been, and remains, a reduction in caloric intake.[103]

Traditionally, the most important aspect of diet and exercise was to ensure that the caloric intake was less than the caloric expenditure, thus producing a caloric deficit.[1] The most commonly recommended diet was the low-fat type. The evidence that dietary composition has an effect on weight loss independent of a reduction in total calories; however, is mixed. There is limited evidence that low-glycaemic and low-carbohydrate diets are both effective, but no single diet has emerged as superior to the others over the long term (i.e., >1 year).[73][103][104][105][106]​​​[107][108][109][110] [ Cochrane Clinical Answers logo ]

Some studies have found that the low-carbohydrate/high-protein diet produces greater weight loss than the low-fat diet at 6-month follow-up, and patients seem to prefer the low-carbohydrate/high-protein diet.[105][106] One meta-analysis looked at results from patients adhering to 14 popular diets, categorised as low-carbohydrate, low-fat, and moderate-macronutrient, and analysed reduction in weight and cardiovascular outcomes at 6 months and 1 year. All three diet patterns resulted in weight loss and decreased blood pressure at 6 months compared with a regular diet; however, these effects largely disappeared after 1 year of dietary adherence.[111]

Adherence to the diet (i.e., compliance) and the reliability of patient reporting of caloric intake have been problematic in studies on dietary intervention. The list of diets in the accompanying table is not intended to be exhaustive.[Figure caption and citation for the preceding image starts]: Dietary options, part 1 of 2Courtesy of Mark Carlson, MD; used with permission [Citation ends].com.bmj.content.model.Caption@7edfcd79[Figure caption and citation for the preceding image starts]: Dietary options, part 2 of 2Courtesy of Mark Carlson, MD; used with permission [Citation ends].com.bmj.content.model.Caption@7297521c

Increase in physical activity

Meta-analyses have indicated that weight loss is greater in diet plus exercise regimens than in diet-only regimens.[102][112] Exercise regimens alone without reduced-calorie diets are not effective for weight loss.[102]

If the patient is physically capable, moderate physical exercise is introduced with 5 sessions per week for 30 minutes per session, in combination with strength training.[113][114] This can be increased as tolerated. In addition, an increase in other physical activity (e.g., taking the stairs instead of the lift) should be encouraged.[1][101] An abundance of supervised and non-supervised exercise programs are available in which a patient could participate. World Health Organization guidelines for physical activity in adults of all age groups are outlined in the primary prevention section, and may be applicable to those seeking treatment for obesity.[92]

See Primary prevention.

A description of common physical activities and their respective rate of caloric expenditure is given, so that the healthcare provider can appreciate the level of expenditure that various physical activities can produce.

[Figure caption and citation for the preceding image starts]: Physical activitiesCourtesy of Mark Carlson, MD; used with permission [Citation ends].com.bmj.content.model.Caption@68e25c33

Adjunctive psychological therapy

Adding psychological therapy is an effective adjunct to diet and exercise, and is recommended in all receptive patients.[1][115][116] Psychological intervention appears to be most effective when it is in the form of behavioural or cognitive behavioural therapy, and is prescribed as an adjunct to diet and exercise.[117][118] Psychological therapy also seems to be best when given in person by a therapist compared with self-directed therapy.[119]

In addition, the practice of frequent self-weighing appears to have a beneficial effect on weight loss.[120]

Web-based behavioural interventions may provide useful educational tools for the achievement and maintenance of weight loss, and the prevention of excessive weight gain.[121][122][123]​​​​ 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]​ In addition, interactive social media platforms that bring together a community to achieve a specific health goal have been found to increase physical activity, weight loss, and overall wellbeing scores. These effects may be amplified when online platforms are combined with regular follow-up on progress from another support provider, either via telephone or in person.[126][127]​​​​ Despite their initial promise, however, further research is needed to determine the long-term effectiveness of such interventions.

Adjunctive pharmacotherapy

Pharmacotherapy 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]​ Originally approved for the treatment of type 2 diabetes, semaglutide is now also 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

  • 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.

Semaglutide is administered as a weekly subcutaneous injection. 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. Semaglutide is also available as an oral formulation; however, this is only currently approved for the management of type 2 diabetes. See Emerging treatments.

Liraglutide, another GLP-1 receptor agonist, is approved for the same indication as semaglutide. In the UK, NICE recommends liraglutide as an option for adults only if they have 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]​ Liraglutide is also administered as a subcutaneous injection, but requires daily administration. When combined with lifestyle interventions, such as participating in a regular physical activity programme, liraglutide has demonstrated efficacy in reducing weight and improving metabolic control in a number of clinical trials involving obese or overweight patients with or without diabetes.[137][138][139]​​​ Weight loss is significantly increased when liraglutide is combined with exercise compared with lifestyle interventions or liraglutide therapy alone.[140] 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] However, 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 lipase). It is approved for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. 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]

Naltrexone/bupropion is an oral combination therapy containing naltrexone, an opioid receptor antagonist, plus bupropion, a noradrenaline-dopamine reuptake inhibitor. It is approved for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. In clinical trials, naltrexone/bupropion was effective in reducing weight compared with placebo when administered in conjunction with lifestyle interventions.[149][150][151][152][153]​ Naltrexone/bupropion should be avoided in patients with seizure disorders or substance misuse disorders. It should be used with caution and at lower doses in patients with hepatic or renal impairment.

Phentermine/topiramate is an oral combination therapy containing phentermine, an amfetamine/appetite suppressant, and topiramate, an anticonvulsant. It is approved for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. Phentermine/topiramate is effective in reducing weight when combined with lifestyle interventions, and may also improve markers of cardiovascular system function such as blood pressure, total cholesterol, triglycerides, and blood glucose levels.[154][155][156][157]​​ Phentermine/topiramate should be used with caution and at lower doses in patients with hepatic or renal impairment, and in 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.

Setmelanotide is a melanocortin 4 (MC4) receptor agonist approved for certain rare genetic conditions that can cause obesity at an early age.[158] 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][159]​​ Setmelanotide works by activating the MC4 receptor, which then initiates a signalling cascade that promotes a feeling of fullness after eating, therefore decreasing excessive caloric intake.[160] Common side effects include gastrointestinal disturbances, headache, injection-site reactions, and skin hyperpigmentation.[158]​ Setmelanotide is also approved for the treatment of obesity and hunger control in patients with confirmed Bardet-Biedl syndrome.[161]

The choice of pharmacotherapy for the treatment of obesity is dependent on multiple variables. Patient comorbidities such as hepatic or renal impairment, history of substance misuse, seizure disorders, and some genetic conditions may prohibit use of one or more of the discussed medications. Moreover, injectable medications may not be appropriate for patients who are unable to administer them safely and independently.

Semaglutide and liraglutide are first-line pharmacotherapy options with clinically proven weight loss and cardiometabolic effects, provided there are no contraindications.[128]​ They are both approved for long-term use. Setmelanotide is a first-line option for patients with POMC, PCSK1, LEPR deficiency, or Bardet-Biedl syndrome. 

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]​ All of these agents are approved for long-term use. 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]

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

Lorcaserin (a serotonin receptor type agonist) had been used for the treatment of obesity in adults, but was withdrawn from the US market because of an increased risk of cancer.[162] ​Lorcaserin was discontinued before attaining approval in Europe.

Bariatric surgery

In general, bariatric surgery (i.e., weight reduction surgery) reduces caloric intake by altering hunger and fullness through surgical alteration of the stomach, small intestine, or both, which produces weight loss. However, the precise mechanism(s) through which a given bariatric procedure results in weight loss is incompletely understood and is undergoing active investigation.[163][164][165]​​​​ One large meta-analysis of outcomes in metabolic-bariatric surgery found that obese patients who underwent bariatric surgery had significantly lower rates of all-cause mortality, compared with obese non-operated controls.[166] This effect was more pronounced in patients with preoperative diabetes than in those without diabetes.[166]​ Evidence is accumulating that bariatric surgery is an effective treatment for type 2 diabetes and hypertension in obese patients.[167][168][169]​​​ The risk of death following bariatric procedures is approximately 0.1%.[170] The overall rate of major complication is approximately 4%.[170]

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 has decreased both 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:[173]​

  • BMI ≥35 kg/m² with or without comorbidities

  • BMI ≥30 kg/m² and type 2 diabetes mellitus

  • BMI of 30-34.9 kg/m² (class I obesity) who do not achieve substantial durable weight loss or comorbidity improvement with non-surgical management.

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]​

Loss of up to 70% of excess body weight has been observed in the first 2 years following bariatric surgery, with significant improvement and even total remission in weight-related comorbidities such as diabetes, hypertension, obstructive sleep apnoea, dyslipidaemia, and cardiovascular disease.[170]​ In addition, bariatric operations are as safe as many other commonly performed laparoscopic procedures today.[170][174][175]​​​ One systematic review found that bariatric surgery is also associated with reduced postoperative prevalence and severity of depression.[176]

In 2019, sleeve gastrectomy (59.4%) was the most commonly performed bariatric operation in the US, followed by gastric bypass (17.8%), revisional procedures (16.7%), intragastric balloons (2.4%), adjustable gastric banding (0.9%), and biliopancreatic diversion/duodenal switch procedures (0.9%).[170] Roux-en-Y gastric bypass may be more efficacious than gastric banding, but the latter may have less morbidity.[177][178][179]​ In one study assessing 5-year outcomes following Roux-en-Y gastric bypass or laparoscopic duodenal switch in patients with a BMI of 50 to 60 kg/m², duodenal switch resulted in greater weight loss compared with gastric bypass but was associated with more surgical, nutritional, and gastrointestinal adverse effects.[180] Further trials are needed.

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 adjustable gastric banding, but less than the gastric bypass.[181] One study found that at 8 years postoperatively, sleeve gastrectomy patients had satisfying weight loss results, demonstrating a 55% mean reduction in excess body weight. However, almost 50% of patients had some degree of weight regain.[182] Weight regain was positively correlated with increased postoperative maladaptive eating patterns and lifestyle habits.[182] Another long-term outcomes study found that over 10 years, all bariatric procedure types were associated with sustained weight loss.[183] However, some series show sleeve gastrectomy failure rates as high as 51.4% and conversion rates to Roux-en-Y gastric bypass, due to weight regain or reflux disease, as high as 36%.[184][185]

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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