Treatment of Obesity

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The treatment of the obesity must be integrated and multidisciplinary in order to achieve and maintain a healthy weight. Weight losses of at least 5-10% in a period of 6 months improve and control the appearance of other diseases (comorbidities) associated with obesity.

The initial treatment of obesity includes changes in eating habits and an increase in physical exercise. Together with these strategies and, depending on the level of obesity, drugs could be administered or bariatric surgery chosen with the aim of boosting the weight loss.

Apple

Diet. There is no single diet pattern to lower weight. Together with the dietician-nutritionist, a balance and varied diet plan is designed to control the calories, which is individualised depending on the level of obesity, the presence of other diseases, age, the level of physical activity, and the preferences of each person.

  • Reduce the calorie supply. The key to lower weight is to reduce the amount of calories consumed. By means of an interview with a dietician, eating and drinking habits can be reviewed with the aim of estimating the amount and type of calories ingested, as well as to establish specific strategies to reduce them.
  • Choose healthier foods. In order to have a healthier diet pattern, one should increase the consumption of plant products such as greens, vegetables, fruit, whole grain cereals, and pulses. If consuming small amounts of fat, ensure that they are from sources that are healthy for the heart, such as olive oil, dried fruits, and blue fish. The consumption of animal products must be much reduced, giving priority to lean meats such as white fish, white meat, and dairy products with a low fat content. It is advised to limit the consumption of red meats and their derivatives, as well as the addition of salt and sugar.
  • Limit the consumption of high calorie foods. Foods high in saturated fats such as fatty cold meats, pastries, cakes, and pre-cooked foods, cold drinks with sugar, as well as alcoholic ones, are a sure way of consuming more calories, thus to limit them or remove them completely from the diet is advisable in order to begin reducing the consumption of calories.
  • Plan meals. Fractionating meals well, keeping regular schedules and balancing feedings.
Man running; regular physical exercise

Physical Exercise. Physical activity adapted to the possibilities of each individual and practiced regularly contributes to help control weight, to improve the associated risk factors, and positively influences the feeling of well-being. To increase the levels of physical activity it is recommended:

  • To plan the physical exercise. It is recommended to start practicing physical activity for at least 150 minutes per week and to gradually increase its duration, intensity, and variety, so as to improve resistance and physical status. Some recommended activities are, to walk fast, ride a bicycle, to swim, to practice pool gymnastics, or to dance The type of physical exercise can also be varied and perform toning / strength and flexibility / balance exercises.
  • Reduce sedentarism. To be active provides great benefits. It is recommended to walk up the stairs instead of taking the lift, park further away from home, occupy yourself with chores in the home and in the garden, be active in leisure time…

Pharmacological treatment of Obesity

According to the recommendations of the scientific societies, pharmacological treatment is recommended as an adjuvant to the treatment with diet and exercise in individuals with a BMI greater than 30 kg/m2 or 27 kg/m2 with at least one disease associated with obesity (dyslipidaemia, high blood pressure, or fatty liver).

The aim of this treatment is to help in the adherence to the changes in lifestyle and to induce and maintain weight loss by overcoming the biological adaptations that occur after weight loss.

The treatment requires a medical indication and supervision. In Spain, the drugs approved for the treatment of obesity are:

  • Orlistat: marketed in 1999. Its main mechanism of action is a reduction, at intestinal level, of 30% of absorption of fat consumed. Its trade name is Xenical or Alli and the dosage is 120 mg once a day. Its main adverse effects are gastrointestinal such as faecal urgency, flatulence, and smelly faeces.
  • Liraglutide: marketed in 2016. Its main mechanism of action, on being an antagonist of human Glucagon-like Peptide-1 (GLP-1) with a longer half-life compared with that secreted by the body, has anorexigenic effects that help it to regulate the appetite.  Its trade name is Saxenda 3 mg, subcutaneous. A lower dose version of 1.8 mg has been approved since 2012 for the treatment of type 2 diabetes. It is recommended to start with low doses and titrate to the maximum dose within 4-6 weeks to preferably avoid nausea. The main adverse effects are nausea, diarrhoea, constipation, vomiting, decrease in appetite, and a reduction in the blood sugar levels.
  • Bupropion/naltrexone: marketed in 2017. Their main mechanism of action is to reduce the pleasurable sensation associated with food consumption, as both active ingredients act on areas of the brain that control intake and caloric balance. When administered together, they reduce appetite and the amount of food ingested, while increasing energy expenditure. Its trade name is Mysimba and the tablets contain 7.8 mg of naltrexone and 78 mg of bupropion. It is recommended to start one tablet a day in the morning and titrate to the recommended dose of 2 tablets twice a day in 4-6 weeks to preferably avoid nausea.The patients that follow this treatment must be subjected to regular monitoring of the response and tolerability of the drug. It must be stopped if there are certain adverse effects, such as an increase in blood pressure or, if after 4 months of treatment, they have not lost at least 5% of their initial body weight. It is currently considered to be a drug with an unfavorable benefit-risk ratio.

Surgical treatment of Obesity

Bariatric surgery (BC) is a group of surgical procedures for the treatment of severe obesity. Bariatric surgery is currently the only effective treatment to achieve a significant and sustained weight loss.

Although bariatric techniques continue to advance, in Spain, the most common techniques are currently:

Tubular gastrectomy

Tubular (or sleeve) gastrectomy. Consists of removing approximately 80% of the stomach so that the remaining stomach acquires a tubular shape (resembles a banana). Among the postulated weight loss mechanisms of this technique are: the significant reduction in food ingestion (and, thus, calories) that can be consumed, on reducing the volume (capacity) of the stomach, as well as the effect the surgery has on gastrointestinal hormones that have an impact on a series of factors that include hunger and satiety.

Gastric bypass

Gastric bypass. Considered the “gold standard” of bariatric surgery. The configuration of this technique is highly effective since it includes a restrictive component with a limitation of oral ingestion, and malabsorptive, with a calorie absorption limitation. Another proposed weight loss mechanism is that, on diverting the passage of food of the proximal portion of the small intestine, changes are produced in the gastrointestinal hormones that promote satiety and hunger.

Gastrectomy and bypass

Duodenal switch or biliopancreatic bypass. It consists of performing, on the one hand, a sleeve gastrectomy and, on the other, a biliopancreatic bypass by means of which the gastrointestinal secretions are shunted at the end of the small intestine (100 cm), which significantly alters the absorption of foods. On being a more malabsorptive technique, it achieves a greater weight loss compared with the two previous techniques, but it can also have a higher risk of complications like diarrhoea, nutritional deficiencies and protein-calorie malnutrition.

Cognitive-behavioral psychological treatment of obesity.

Psychological factors contribute to the development and/or maintaining of overweight and obesity. They also make it difficult to start and maintain a weight loss treatment.

On the one hand, some people eat more, and less healthily, when they are in negative emotional states, such as anxiety and sadness. Eating can act as a mechanism to confront certain situations that, although it can initially alleviate negative emotions, it finally ends up being a problem. On the other hand, individuals with obesity have a higher risk of having psychological changes. The most common are depressive, anxiety, and eating disorders, as well as those related to substance use. Furthermore, they tend to suffer difficulties of self-esteem and self-image, and in relationships with others.

Cognitive-behavioural psychotherapy is the most effective. The main purpose of the treatment of obesity is to help in the changing, the acquiring, and maintaining of behaviours that enable an improvement in the psychosocial functioning of the patient, as well as a reduction in weight and maintaining it. To identify these situations, external or internal (mental or emotional) that predispose to eating inadequately and provide the patient with behavioural, emotional, and cognitive strategies that help them to have a healthier relationship with food.

The techniques used in this therapy are conceived for the management of anxiety, the resolving of problems, for controlling stimuli, for self-control, and for cognitive restructuring, among others.

New therapies

Despite the fact that the obesity epidemic is mainly explained by environmental factors - for example, the intake of a high calorie diet or a sedentary lifestyle - the discovery of other factors, such as genetic ones or the alteration of gut microbiota have opened up the possibility of new therapeutic avenues.

Regarding drug treatment, scientific research focuses on 3 mechanisms: decrease in calorie intake/absorption, increased energy expenditure and modulation of fat deposition in the body.

Semaglutide (Ozempic) and exenatide (Bydureon) are GLP-1 receptor agonists with marketing authorisations in Spain for the treatment of type 2 diabetes mellitus. Both drugs are in development for the treatment of obesity. Exenatide is a short-acting GLP-1 analogue and does not therefore provide substantial treatment benefits compared to liraglutide. Semaglutide is a long-acting GLP-1 analogue of subcutaneous treatment (0.25 mg to 1.0 mg per week). An oral application is also being developed, which would make the drug much more attractive to patients. Both semaglutide and exenatide provide comparable or even greater efficacy than liraglutide treatment. Both drugs are in phase II trials and marketing approval for obesity is expected in the near future.

There are also other agents under investigation, targeting special pathways involved in the development of obesity. Some examples of promising agents are: (these drugs represent only a few candidates in the obesity drug arsenal): melanocortin-4 receptor agonists (RM-493); NPY inhibitors (the obinepitide Y2/Y4 receptor agonist and a selective Y4 receptor agonist TM30339); sympathomimetics (tesofensin), combinations of GLP-1 and PYY3- 36 agonists; lipase inhibitors with minor side effects (cetilistat, marketing authorisation already granted in Japan), β3 adrenergic receptor agonists (LY-377604 + sibutramine); angiogenesis inhibitors (ALS-L1023); sirtuin 1 activators (SIRT1), cGMP-targeting molecules (sildenafil and linaclotide); and various dual receptor agonists such as tirzepatide, which is a dual GIP receptor (peptide gastrin inhibitor) and GLP-1 currently in development.

Endoscopic treatments are minimally invasive and increasingly better tolerated and effective in the short term in achieving weight loss. Currently, they are used when the patient is unwilling or ineligible for bariatric surgery, or as initial weight loss treatment in patients at high surgical risk. Since 2016, several endoscopic devices have been approved for the treatment of obesity, such as the Orbera intragastric balloon and the dual balloon whose mechanism of action is restrictive as they are devices that occupy space and reduce the capacity of the stomach. The Aspire Assist consists of the aspiration of one third of the gastric contents after each meal through a gastrostomy tube with a single valve, known as the AspireAssist.

There are many candidate genes for gene therapy in obesity. Using observational data in animals deficient in leptin (a hormone released from fat tissue informing the hypothalamus of energy reserves), subjects treated with physiological doses of recombinant leptin have demonstrated successful weight loss.

Restoration of the gut microbiota through the use of prebiotics, probiotics and faecal transplantation are being investigated for weight loss in the treatment of obesity.

Substantiated information by:

Alba Andreu Martí
Lilliam Flores Meneses
Silvia Cañizares Alejos

Published: 17 August 2018
Updated: 20 January 2022

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