Medical management of obesity

Sheena Gupta and Mimi Chen
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DOI: https://doi.org/10.7861/clinmed.2023-0183
Clin Med July 2023

Abstract

Obesity is a global epidemic that has worsened over the past few decades. It is strongly associated with multiple health conditions, including type 2 diabetes mellitus, cardiovascular diseases, obstructive sleep apnoea, certain malignancies and has an increased mortality risk. The annual cost of obesity to the NHS is around £6 billion, projected to increase to just under £10 billion by 2050. In 2020–2021, obesity was cited as a factor in over 1 million hospital admissions. An early and pragmatic approach to the management of obesity would reduce obesity-associated multiple health conditions and result in cost savings for the NHS. Here, we discuss current management strategies for obesity, including dietary intervention, pharmacological therapies and optimisation, and bariatric surgery.

KEYWORDS:

Introduction

The Health Survey for England 2021 reported that 64% of adults are overweight or obese, and that men were more likely to be overweight or obese compared with women (69% versus 59%).1

People living with obesity are 2.5 times more likely to have hypertension, five times more likely to develop type 2 diabetes mellitus (T2DM), and have an increased risk of malignancies, such as colon cancer.2 Life expectancy is predicted to be reduced in individuals with a body mass index (BMI) over 40 kg/m2 by ∼8–10 years.3 Government estimates indicate that the current cost of obesity to the NHS is £6.1 billion and £27 billion to wider society.4 A recent study suggests that even a 2.5 kg weight loss in overweight or obese individuals in the population could save the NHS £105 million over 5 years.5

The time it takes patients to seek help for obesity management can vary greatly because of both sociocultural factors and country of residence.6 Studies have also shown that there is a perceived disparity in the quality of healthcare received and their interaction with healthcare professionals for individuals who are overweight or obese.7

A greater understanding of obesity and an increased awareness of obesity-related multiple health conditions from patients and healthcare professionals can lead to earlier tailored non-clinical and clinical interventions. This will subsequently help to prevent the development of certain health conditions and improve patients' quality of life.

Tiered weight management system

Within the NHS, the weight management service is delivered through a structured tier system (Fig 1). It signposts healthcare professionals to utilise all available resources and public health input, such as promoting healthy eating and physical activities (Tier 1). Non-clinical interventions, such as community-based weight management programmes and primary care team provision of dietician input and weight loss medication, fall into Tier 2. Escalation to specialist weight management services that provide medical and surgical interventions forms Tiers 3 and 4 respectively.8

Fig 1.
Fig 1.

The tiered weight management system in England.8 AOM = anti-obesity medication.

Multidisciplinary approach to obesity

Patients with obesity can and often present with cardiovascular, respiratory, and renal disease, as well as mental health disorders, such as depression or disordered eating. Therefore, it is imperative to assess and identify associated health conditions. Certain investigations and assessments may be appropriate to perform. Examples include echocardiography and lung function tests, checking a patient's pro-brain natriuretic peptide (BNP) level and assessing their snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck size, gender (STOP-BANG) score for obstructive sleep apnoea. These can help guide physicians to refer to the appropriate specialities as well as to the Tier 3 and 4 obesity services. In certain trusts, joint speciality clinics, such as cardiometabolic clinics, are available. These clinics provide a collaborative assessment and management of high-risk patients with multiple health conditions, aiding weight loss as well as reducing morbidity.

A multidisciplinary team (MDT) is involved in the management of obesity within Tiers 3 and 4. There is significant variance in how obesity services are run in different NHS Trusts and which specialists are involved. Table 1 briefly describes the role of team members who usually contribute to the MDT.9

View this table:
Table 1.

Roles of multidisciplinary team members in Tier 3 and 4 obesity services9

Dietary intervention

Weight loss occurs when energy expenditure is greater than energy intake. Overall, calorie intake reduction with increased physical activity remains the mainstay of intervention to manage weight loss. An average deficit of 500 kcal/day is likely to result in an initial weight loss of ∼0.5 kg/week.10

Various diets have been proposed for weight loss, including the Mediterranean diet, low calorie-intake diet (800–1200 kcal/day), very low-calorie intake diet (VLCD; 200–800 kcal/day), low-fat diet, low-carbohydrate diet, and high-protein diet. These diets can all lead to weight loss as long as there is an overall calorie deficit.11 National Institute for Health and Care Excellence (NICE) guidelines recommend a calorie deficit of at least 600 kcal/day for sustainable weight loss.12 The decision on which diet to follow is based on the patient's preference as well as the ability to maintain weight loss by adhering to the dietary changes. Diet choices can be supported by discussion with a skilled dietician.

The low-calorie intake diet was implemented in the DiRECT randomised controlled trial, which assessed remission of T2DM during a primary care-led weight management programme. At 24 months, 11% of intervention group participants had a weight loss of at least 15 kg, compared with 2% of control group participants. Furthermore, 36% of participants in the intervention group had remission of diabetes compared with 3% in the control group.13

VLCD is not necessarily superior to other diets in terms of long-term weight loss. A meta-analysis of six trials comparing VLCD to conventional low-calorie diets showed greater short-term weight loss (16.1 versus 9.7% of initial weight) but no significant difference in long-term weight loss (6.3 versus 5%). Rapid weight gain was also reported once the diet was stopped. Side effects, such as hair loss, coldness, and skin thinning, are frequently experienced.14 Therefore, VLCD is only recommended when rapid short-term weight loss is required for a specific purpose, such as before surgery.12

In the UK, individuals can refer themselves or be referred by their GP to a Tier 2 weight management programme. This comprises a local service providing diet, lifestyle, and behavioural change advice, normally in a group setting. It is usually funded by the local authority for a total of 12–24 weeks. Public health data from 2021 to 2022 reported that 43% of Tier 2 participants lost weight by the end of their service, with 17% having lost at least 5% of their initial body weight.15

Optimisation of medications

Several classes of medication are associated with weight gain, principally antipsychotics, mood stabilisers, antidepressants, corticosteroids, and some anti-glycaemic agents. It is often helpful and recommended for healthcare professionals to perform a medication review and assess whether certain medication could be contributing to weight gain; and whether these could be substituted with an alternative medication or discontinued.

Psychiatric medication

Antipsychotic medication use can frequently contribute to significant weight gain, although the extent varies widely among different agents. For example, clozapine (4.5–16.2 kg) and olanzapine (3.6–10.2 kg) have been found to lead to the highest weight gain and, conversely, aripiprazole (–1.4 to +0.2 kg) and risperidone (0.4–2.1 kg) comparatively lead to lower weight gain.16

Lithium and sodium valproate, commonly prescribed to treat bipolar disorder, can also be associated with marked weight gain (1.1–9.9 kg and 0.7–6.9 kg respectively), whereas lamotrigine (–4.2 to +0.6 kg) and carbamazepine (–3.1 to +0.4 kg) are weight neutral or can even lead to weight loss.16

Antidepressants are associated with less weight gain compared with antipsychotic medications and are more frequently prescribed. Amitriptyline (0.4–7.3 kg) and citalopram (–0.1 to +7.1 kg) are associated with the highest weight gain, compared with sertraline (–1.6 to +1.0 kg) and fluoxetine (−1.3 to +0.5 kg), which are generally weight neutral.16

Diabetes medication

The risk of developing diabetes is seven times greater in people living with obesity compared with those of a healthy weight.17 Good management of diabetes should include weight management. Different antidiabetic medications can lead to weight loss or weight gain.

Metformin can lead to an average weight loss of 1–2.9 kg, and sodium-glucose co-transporter-2 inhibitors (SGLT2i) lead to even greater weight loss. The highest weight loss is observed in patients taking canagliflozin (1.9–4.0 kg), followed by dapagliflozin (1.0–4.5 kg) and empagliflozin (1.5–2.9 kg).16

NICE advises that patients with type 2 diabetes mellitus (T2DM) and obesity are prescribed a glucagon-like peptide-1 receptor agonist (GLP-1 RA) if triple therapy with other glycaemic agents is not effective, tolerated, or contraindicated.18 Weight loss achieved with GLP-1 RAs is discussed below.

Weight gain is a well-known side effect of insulin and can range from 0.4 to 4.8 kg. Insulin detemir leads to less weight gain and equivalent glycaemic control compared with Neutral Protamine Hagedorn (NPH) insulin (0.4 kg versus 1.9 kg respectively over 6 months).19 Sulfonylureas are commonly associated with weight gain and can result in a gain of ∼4.2 kg over 2 years.20 Therefore, alternatives, such as SGLT2i and/or GLP-1RA agents, should be considered instead of sulfonylureas in patients who are overweight or obese.

Steroid use

Long-term steroid use is linked with significant weight gain; however, short-term use is not. Therefore, it is advised to reduce the duration of steroid use or use steroid-sparing agents if feasible.16

In summary, optimisation of medication alone might be enough in some patients to achieved required weight loss. Furthermore, medications with similar efficacy but that are weight neutral or have known weight-loss benefits are preferred in patients with a raised BMI.

Pharmacological agents for weight loss

NICE recommends consideration of pharmacological therapy if weight loss is suboptimal despite lifestyle modifications, including dietary changes and increased physical activities. However, currently licenced and NICE recommended weight-loss agents are limited to orlistat and GLP-1RAs.12 Other therapeutic agents can be initiated by specialist weight management services.

Orlistat

Primary care can offer patients orlistat, a pancreatic lipase inhibitor. Orlistat leads to a dose-dependent decrease in fat absorption, inhibiting the absorption of ∼30% of calories ingested from fat, which is then excreted via faeces.21 To be eligible for orlistat, a patient is required to have a BMI ≥28 kg/m2 with associated obesity-related multiple health conditions, or with a BMI of ≥30 kg/m2. It is usually prescribed for 12 months except in patients awaiting bariatric surgery.12

The Xendos study, a double-blind, randomised controlled trial, found that orlistat plus lifestyle modification led to significantly more weight loss compared with placebo plus lifestyle modification (−10.6 kg versus −6.2 kg at 1 year, respectively; and −5.8 kg versus −3.0 kg after 4 years, respectively). Furthermore, the orlistat group had a 37% relative risk reduction of T2DM.22 More recently, orlistat has been shown to reduce major cardiovascular events, new-onset heart failure, renal failure, and mortality.23

Therefore, orlistat should be considered as first-line therapy in the community for weight management, and perhaps considered as primary prevention in individuals with obesity and high cardiovascular risk. Unfortunately, the gastrointestinal side effects of oily stool and faecal incontinence are the most frequent reasons for discontinuing orlistat.22

GLP-1 receptor agonists

GLP-1RAs are a class of medication that was originally developed to treat T2DM but was also found to be effective for weight loss in patients without diabetes. GLP-1RAs work by mimicking the effects of GLP-1 in the body, which can lead to increased insulin secretion, decreased glucagon secretion, and slowed gastric emptying, with increased satiety and decreased appetite. These effects can lead to a reduction in food intake and subsequent weight loss.24 Gastrointestinal side effects are common, and there is small associated risk of developing cholecystitis and pancreatitis. Therefore, GLP-1RAs should be used with caution in patients with a history of previous pancreatitis or existing gallstones.

In 2021, NICE approved the use of once-daily liraglutide (Saxenda®) injections for weight loss in patients with a BMI >35 kg/m2, prediabetes, and high cardiovascular risk factors. Patients who are from Black, Asian, and other minority ethnic groups are eligible for liraglutide with a BMI of 32.5 kg/m2 with the above multiple health conditions.25

Liraglutide can only be prescribed by a secondary-care Tier 3 weight management service. A Tier 3 service referral is for individuals with obesity (usually with a body mass index ≥35 kg/m2 with multiple health conditions or ≥40kg/m2 with or without multiple health conditions) who have not responded to previous Tier 2 interventions. The maximum duration of a prescription under the NHS is limited to 2 years, and it is recommended to only continue prescribing the medication if there is a 5% weight reduction within the first 6 months.25 Liraglutide is also licenced as Victoza® for the management of T2DM.

In the SCALE double-blind, randomised controlled trial, weight loss of 5% or greater occurred in 54.3% of participants treated with liraglutide (3.0 mg) and 40.4% with liraglutide (1.8 mg) versus 21.4% with placebo. Weight loss greater than 10% occurred in 25.2% treated with liraglutide (3.0 mg) and 15.9% treated with liraglutide (1.8 mg) versus 6.7% treated with placebo.26

NICE recently approved the use of weekly semaglutide (Wegovy®) injections, with the same eligibility criteria as liraglutide (Saxenda®). 27 Semaglutide is licenced as Ozempic® for use in T2DM. Clinical trials showed that semaglutide leads to more weight loss compared with liraglutide. The STEP-1 randomised controlled trial reported that more participants in the semaglutide group compared with the placebo group achieved weight reductions of 5% or more (86.4% versus 31.5%), 10% or more (69.1% versus 12.0%), and 15% or more (50.5% versus 4.9%) by week 68.28 However, the prescribing of GLP-1RAs may be restricted depending on regional formulary status as well as stock shortages.

An increasing number of studies are recommending longer term use of GLP-1RAs to ensure weight-loss maintenance and, even more importantly, for the continued cardiovascular benefits in patients with obesity.29

Dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists

Tirzepatide is the first dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-RA. It is currently licensed to treat T2DM in the USA. It was shown to be associated with an even greater weight reduction compared with semaglutide (1 mg), as discussed elsewhere in this special issue.

In an open-label trial, varying doses of once-weekly tirzepatide were compared with semaglutide 1 mg. At 40 weeks, reduction in body weight with all doses of tirzepatide was greater compared with that achieved with semaglutide (5, 10, and 15 mg of tirzepatide; −7.6, −9.3, and −11.2 kg, respectively: 1 mg of semaglutide; −5.7 kg). However, no participants received semaglutide 2.4 mg once-weekly dose, which is the recommended dose for obesity treatment.30

In summary, with the development of safer and more potent therapeutic agents, patients who are otherwise unsuitable for invasive procedures, or prefer not to, could benefit from medical weight management to achieve their weight loss goals.

Bariatric surgery

Bariatric surgery should be considered for patients with severe obesity who cannot achieve sustainable weight loss. In the UK, the most offered procedures are laparoscopic gastric banding, sleeve gastrectomy, and Roux-en-Y bypass surgery.

Since the COVID-19 pandemic, a significant proportion of the population have gained weight.31 In 2019–2020, 5,741 people in England had bariatric surgery because of obesity. However, this fell during the COVID-19 pandemic, to 1,596 people in 2020–2021 and 4,035 people in 2021–2022. Since the pandemic, there is now a much longer waiting list for bariatric surgery under the NHS across the country. Delayed treatment could lead to the development or worsening of obesity-related health conditions.32

NICE guidelines recommend that patients are referred for a bariatric surgery assessment if they have a BMI of 40 kg/m2 or above, or 35 kg/m2 and above with associated multiple health conditions (such as cardiovascular diseases, diabetes, and obstructive sleep apnoea) that can be improved with marked weight loss. Lifestyle modifications and pharmacological interventions are recommended before referral to a Tier 4 bariatric service. Bariatric surgery is the first-line treatment option for individuals with a BMI >50 kg/m2.12

Patients with certain medical or mental health conditions might not be suitable for bariatric surgery when the risks outweighs the benefits. Therefore, the patient's suitability for surgery needs to be assessed by specialists in weight management MDTs, including bariatric physicians, dietitians, psychologists, anaesthetists, and surgeons. The patient can proceed with bariatric surgery only after an MDT agreement and with a plan for postoperative follow-up.

Combined with ongoing lifestyle modifications, bariatric surgery is very effective for long-term weight loss. Twenty-year follow up in the Swedish Obesity Study (SOS) showed that patients who underwent bariatric surgery maintained an overall significant amount of weight loss, with Roux-en-Y bypass surgery resulting in the greatest weight loss compared with gastric banding and sleeve gastrectomy (Fig 2).33

Fig 2.
Fig 2.

Mean percentage weight change from baseline among patients in the control and three surgery groups during 20 years of follow-up in the Swedish Obese Subjects study. Data shown for controls receiving usual care and for surgery patients undergoing banding, vertical banded gastroplasty (VBG), or Roux-en-Y gastric bypass (GBP) at baseline.33

Although bariatric surgery is the most effective treatment option for obesity, it can be associated with significant surgical and anaesthetic risks and complications. In an experienced bariatric centre with a large operative volume, the mortality rate associated with bariatric surgery can be as low as 0.03%, similar to that of a cholecystectomy. However, the risks increase in patients with extremely high BMIs, for example >70 kg/m2, and in the hands of less-experienced surgeons.34 Bariatric surgery can also lead to nutritional deficiencies and therefore requires lifelong supplements.

Table 2 summarises the three most commonly performed bariatric surgery interventions, with approximate weight loss achieved, diabetes remission rates, and complications.34–37

View this table:
Table 2.

Summary of the three most commonly performed bariatric surgery interventions

Conclusion

Managing obesity should be a collaborative approach by all healthcare professionals with the patient being at the centre of the decision-making process. Understanding the pros and cons of the different treatments will help patients and healthcare professionals to individualise a stepwise treatment plan, including both non-clinical and clinical interventions. Keeping ourselves, as healthcare professionals, up-to-date with novel therapies, and promoting earlier and customised interventions for obesity will enhance clinical outcomes as well as lead to cost savings for the NHS in the long-term.

Key points

  • Obesity is increasing in prevalence and is associated with multiple health conditions, costing the NHS £6.1 billion annually.

  • Weight management services within the UK are delivered through a four-tiered system, which allows healthcare professionals to utilise all available resources in a stepwise manner to support patients living with obesity.

  • A calorie deficit is necessary for weight loss, and can be achieved by various dietary plans, but the only effective changes are those that are sustainable and nutritionally balanced.

  • Pharmacological interventions include optimisation of medications and use of weight-loss medication, such as orlistat and glucagon-like peptide-1 receptor agonists.

  • Bariatric surgery is the most effective treatment option for obesity, but it can be associated with significant surgical and anaesthetic risks and requires input from an appropriate weight-management multidisciplinary specialist team.

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Medical management of obesity
Sheena Gupta, Mimi Chen
Clinical Medicine Jul 2023, 23 (4) 323-329; DOI: 10.7861/clinmed.2023-0183
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