Clinical FeaturesEndocrine/Metabolic

Obesity: The Disease and the Available Treatments

Written by Dr Karl J Neff  – St Vincent’s Health Group, Dublin Diabetes Complications Research Centre, Conway Institute, University College Dublin

Obesity is a disease that affects all facets of health and wellbeing, and is associated with a wide range of diseases, including type 2 diabetes, cardiovascular disease and cancer. 1, 2 The morbidity associated with obesity is so significant that it limits life expectancy. 3

As well as the effects on physical health, obesity has chronic and debilitating effects on psychosocial health and function. Obesity is associated with poor mental health outcomes, reduced social participation, reduced economic opportunity, and reduced quality of life. 4-5

The negative effects of obesity on psychosocial function and health are partially attributable to obesity stigma. Obesity stigma is the term used to refer to discrimination based on weight. In our society, many feel free to openly discriminate against people based on their weight. People with obesity are very likely to encounter stigma both in everyday life and in healthcare encounters.

Obesity stigma manifests in many ways. It most commonly manifests in public life in media commentary that describes people with obesity as ‘fat and lazy’ that could (but won’t) make better food choices and do more exercise in order to lose weight. This narrative leaves people living with obesity feeling very alone in a world that judges them for their disease.

In healthcare, we are just as prone to obesity stigma as any other section of society. People with obesity often avoid presenting to healthcare providers with medical symptoms as they expect that every symptom will be attributed to their weight, and that they will not be listened to. Instead they will likely be told that things would get better if they would ‘just lose some weight’: something that they have probably heard and tried to do many times before (usually without success).

Obesity stigma is a result of a fundamental misunderstanding of obesity as a moral choice rather than a disease. For the majority of people with obesity, the physiological regulation of body fat is dysfunctional and metabolic maladaptation has developed that prevents sustainable weight loss.

This means that when people with obesity try to lose weight, physiological mechanisms are activated that defend against loss of body fat. In obesity, the hypothalamus (the energy homeostat of the body) has lost the ability to accurately gauge the amount of body fat present, and so responds to reduced food intake as part of a planned calorie controlled diet in the same way as it would response to starvation: it activates two powerful physiological systems that prevent weight loss. 6-8

The first physiological defence mechanism is hunger. Reduction in food intake results in increased hunger. Hunger is an unconscious physiological reflex that can be consciously controlled to an extent. People on a diet consciously resist their hunger in an effort to lose weight. For people who do not have obesity, this can be done with relative ease. If we do not have obesity, then the hypothallus recognises the adipose stores present and so moderates any increase in appetite.

However, people with obesity will be persistently hungry, and often have increased hunger, while on a diet. 6-8 While they can consciously resist their hunger, with great effort, to achieve at least some weight loss, living in a constant state of perceived starvation is challenging to maintain.

For those that do sustain long term resistance of hunger, and achieve weight loss, the second major physiological maladaptation comes into play. This is alteration of the basal metabolic rate. If hunger does not stimulate calorie ingestion, then the hypothalamus will downregulate the basal metabolic rate so that we burn fewer calories. 8-10

This is why people usually find that despite sticking to a diet that initially resulted in weight loss (while feeling extremely hungry throughout), they ultimately hit a weight loss plateau. This occurs because the energy homeostat adjusts energy expenditure downwards to meet the reduced calorie intake. This means that people will continue to burn fewer calories for as long as there is a net calorie deficit.

The only way to overcome this mechanism is to consciously reduce calorie intake to extremely low levels below the minimum basal metabolic rate needed for survival (i.e. a ‘starvation diet’ which for most equates to less than 600kcal per day). However, even if someone can achieve this, reintroduction of a diet with a calorie intake within recommended limits (e.g. 2000kcal per day) will produce weight regain, as their healthy 2000kcal a day diet will be in excess of the calories that they are expending by the end of their diet (which could be less than 1000kcal per day). 8-10 Therefore, weight regain occurs as they are consuming more calories than they are burning.

Treating Obesity

Given these powerful physiological mechanisms, obesity is a very difficult disease to treat. However, treatment should be actively offered to people with obesity as successful treatment results in improved physical health, with significant benefits in the prevention and treatment of obesity associated diabetes, cardiovascular disease and cancer. These benefits in physical health occur in tandem with myriad benefits in psychosocial health and functioning.

Diet and Exercise Based Approaches

Given the two pathophysiological mechanisms inherent in the disease of obesity described above, it should be no surprise that for the majority of people with obesity, diet and exercise interventions alone will not achieve durable weight loss. Diet and exercise based treatment can be very effective in a small number of people. However, for most people with obesity diet and exercise based approaches are insufficient to treat the disease and result in significant weight loss. 11-14

This is not due to lack of adherence with the programme. Lack of weight loss in response to diet and exercise intervention is usually due to the physiological defences against weight loss described above. 8-10, 12 At best, approximately 20% of people with obesity will achieve significant weight loss with diet and exercise programmes alone, meaning that 80% or more will not. 13

However, diet and exercise programmes are very unlikely to cause harm and so, while ineffective in most people, remain the most reasonable first step in the treatment of obesity. Ideally, a diet and exercise based intervention would be structured and led by a Dietician with support from an Exercise Physiologist and Psychologist. If such a programme is not available, then most commercially available programmes can at least offer clear structured advice on calorie reduction and peer support.

The dietary element of diet and exercise based interventions should be focused on calorie restriction. The mode of restriction, for example alternate day restriction versus daily continuous restriction, seems to be unimportant, with comparable results in the medium to long term. 14 Similarly, the extent of restriction does not seem to be important in determining the ultimate weight loss. Very low calorie diets and more conventional calorie controlled diets have similar medium and long term outcomes. 15

Exercise is an important component of these programmes. This is because it enhances weight maintenance. 16, 17 Exercise does not enhance the initial weight loss but does help to minimise weight regain after a dietary intervention. 16, 17 If possible then individual prescription of exercise by a physiotherapist or an exercise physiologist who specialises in obesity should be included in a diet and exercise programme. A minimum of thirty minutes a day is needed for benefit, and this should involve both aerobic and resistance elements. The resistance element is important to maintain muscle mass during weight loss, as this has been postulated to reduce hunger and aid long-term weight maintenance. 17

Behavioural support is important to aid both weight loss and weight loss maintenance. 18 Peer support is part of this, but individual support offered by a specialist Psychologist can be of significant benefit. The focus should be on adapting food relationships and food environments. Most of us will use food as an emotional regulator, to help with stress management or to help alleviate sadness or anxiety. We build food environments to facilitate this, by keeping a source of ‘comfort food’ nearby for when we need it. For people with obesity, this can compromise their diet and exercise therapy, and so behavioural interventions exploring emotional support and stress management can be an effective component of an obesity treatment programme.

Medical therapy

When diet and exercise based programmes are unsuccessful, medication should be considered as next-line therapy. There are four medical options at present; orlistat, liraglutide (at a dose of 3mg daily rather than the 1.8mg dose used for diabetes), Semaglutide (at a dose of 2.4mg once weekly rather than the 1mg dose used to treat diabetes) and naltrexone/ bupropion. All of these can be prescribed safely in primary care but should be used in combination with, not instead of, a diet and exercise based programme to enhance effectiveness.

Orlistat is an agent that limits fat absorption in the gut, and if used with a sufficiently low fat diet, can result in weight loss of almost 10% with very few side effects. 11 If a low-fat diet is not maintained during treatment then orlistat will cause intolerable steattorrhoea. Therefore, an explanation of how the medication works, and a dietetic review, is advisable prior to starting orlistat to improve the likelihood that the medication will be effective and tolerable.

Both Liraglutide and Semaglutide change hypothalamic regulation of appetite and are more effective in the treatment of obesity than diet and exercise therapy alone. 19, 20 These agents have a variance of effect. Some people will lose significant amounts of weight, comparable with some modalities of bariatric surgery, whereas some will not lose weight at all. When most effective they can produce weight loss in excess of 15%. 19, 20 It remains impossible to predict who will respond to medication but within four months of use it will be clear if the individual will respond to therapy or not.

The combination treatment naltrexone-bupropion, when used with lifestyle interventions, can produce weight loss of up to 10%. 19 The mechanism of action is not entirely understood, but is thought to act via modulation of central appetite and reward pathways. Both naltrexone and bupropion can interact with several other medications and are contraindicated in some medical conditions. Therefore, a comprehensive medical and drug history should be taken prior to prescription, and this combination should only be prescribed under close supervision.

Surgical treatment of obesity

If medical therapy is ineffective, then surgery should be considered. Obesity surgery (also called bariatric or metabolic surgery) is the most effective intervention in treating obesity and obesity-associated disease. All procedures are performed laparoscopically with a very low rate of complications and result in a mean ten-year weight reduction of 25%. 21-23 The weight loss associated with surgery is usually durable and occurs in tandem with significant improvements in multiple health outcomes including a reduction in all-cause mortality.

In metabolic disease, surgery has particular benefits, and is a more effective treatment for type 2 diabetes than medical care alone. 24, 25 Surgery improves glycaemic control but also reduces mortality and maintains control of diabetes in the long-term. 21

Weight loss after surgery is a not a result of physical restriction or calorie malabsorption, as often believed. The major mechanism of weight loss after surgery is increased satiety and decreased hunger as a result of changes in gut hormones. 26, 27 Surgery can also enhance energy expenditure, despite reduced food intake. 28

Therefore, surgery directly ameliorates the two major pathophysiological bases of the disease of obesity.

Surgery is the only treatment with evidence for long-term weight loss, and reduction in all cause mortality, and therefore should be considered in all people with obesity. While the peri-operative risks are low, these procedures are not ‘the easy option’ and are not suitable for everyone. Before proceeding a thorough multidisciplinary assessment is needed to ensure candidates are fully prepared to have an optimal response to surgery and that surgery is a suitable treatment for them.


Obesity is an increasingly prevalent disease that affects all aspects of human health. This results in associated disease, disability and a reduction in life expectancy. However, obesity can be successful treated. The treatment of obesity needs to be individualised, and can include diet, exercise and behavioural interventions, supplemented by medical or surgical interventions. Given that there are treatment options available, people with obesity need to be recognised and offered referral for treatment.

As a healthcare system, we need to do better for people with obesity, both in terms of our understanding of obesity and in the provision of treatment. In 2021, the HSE Model of Care for obesity was launched (https://www.hse. ie/eng/about/who/cspd/ncps/ obesity/model-of-care/) Hopefully, this will be the start of a new programme of expanded public sector provision of all treatment options for obesity so that we help people living with this insidious chronic disease.

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