Phramacotherapy, endoscopic devices, and bariatric surgery for the treatment of obesity

Pharmacotherapy, endoscopic devices, and bariatric surgery for the treatment of obesity

Written by:

Dr Werd Al-Najim, Clinical Nutritionist, School of Medicine, University College Dublin; and ProHealth365 Physiotherapy and Nutrition

Prof Alex Miras, Clinical Professor of Medicine, Ulster University; and ProHealth365 ProHealth365 Physiotherapy and Nutrition

Ms Rand Al-Najim, Chartered Physiotherapist, ProHealth365 ProHealth365 Physiotherapy and Nutrition

Obesity is a chronic relapsing disease that acts as a gateway to many other non-communicable diseases, such as diabetes, cardiovascular disease and cancer. While the prevention of obesity is ideal for lowering the risk of developing these diseases, a large percentage of the population is already living with overweight and obesity. For example, in Ireland, just under 37% of people have a normal weight, six out of ten people are living with overweight or obesity.

The first weight management action most of the population takes is lifestyle intervention.

According to the Health Ireland Summary Report (2019), the most common actions were exercising more, eating fewer calories, and eating/drinking fewer sugarsweetened foods/drinks. These are all significant lifestyle interventions that will improve general health and result in some weight loss but may be challenging to maintain in the long term.

Several other obesity treatment options are available for those who do not respond to selfdirected interventions; these include intensive lifestyle treatment combining nutritional and exercise therapy, pharmacotherapy, endoscopic devices, and bariatric surgery. Patients need to understand the pros and cons of each treatment, the amount of weight loss to be expected, and the lifetime commitment. All obesity treatments require life-long follow-up. In a previous article published by Hospital Professional News, we covered the intensive lifestyle treatment combining nutritional and exercise therapy for obesity. This article will focus on pharmacotherapy, endoscopic devices, and bariatric surgery.

Available anti-obesity medications in Ireland

The use of anti-obesity medications in conjunction with lifestyle interventions is indicated for people with obesity (BMI ≥30 kg/m2) or those who are overweight (BMI ≥27 kg/m2) with at least one weight-related health condition (eg, type 2 diabetes, cardiovascular disease, and osteoarthritis). Several anti-obesity medications are approved by regulatory authorities in Ireland for long-term weight management, summarised in table 1.

Orlistat

Orlistat is a gastric and pancreatic lipase inhibitor marketed under the names XENICAL® 120mg and Alli® 60 mg. This agent was first approved in 1998 to reduce dietary fat absorption by around 30%.

Orlistat is considered one of the safest anti-obesity medications currently available in the market as it is not absorbed from the gastrointestinal tract (GI), however as the fundamental action of the drug is to inhibit digestion and absorption of dietary fat, steatorrhoea can be unwelcomed and un-pleasant reality for patients when they overconsume fatty foods. Orlistat results in weight loss in a dose dependent manner but up to 4% in one year.

Naltrexone SR/Bupropion DR

SR/ Bupropion DR marketed under the name Contrave® in the United States and MysimbaTM in Europe. Naltrexone is an opioid receptor antagonist and Bupropion is a proopiomelanocortin (POMC) neuron stimulator. Taken together, the stimulation of POMC enhances the release of the satiety neurotransmitter α-melanocyte stimulating hormone (α-MSH) in the arcuate nucleus of the hypothalamus. This mechanism is modulated by mu-opioid receptors via an inhibitory feedback loop. Naltrexone blocks this inhibitory feedback thereby enhancing the release of α-MSH. Naltrexone also enhances the activity of the dopaminergic in the nucleus accumbens, ventral tegmental area and pre-frontal cortex, which are thought to be involved in some hedonic (reward) properties of food such as food cravings and improved inhibitory behaviour, resulting in around 5% weight loss.

Glucagon-like peptide-1 (GLP-1) analogue

GLP-1 is an incretin hormone released in response to nutrient ingestion. The class of GLP1 receptor agonists, of which liraglutide (Saxenda®) and semaglutide (Wegovy®) are currently approved for obesity management, inhibit food intake via action at GLP-1 receptors in several CNS areas (particularly the brainstem and hypothalamus) and lead to 8-12% weight loss. Additionally, GLP-1 receptor agonists have peripheral actions, including slowing gastrointestinal transit, enhancing insulin secretion under conditions of hyperglycaemia, and decreasing blood pressure by increasing renal sodium excretion.

Hydrogels and endoscopic procedures

Endoscopic devices and oral hydrogels were developed to fill the gap in obesity management for people who are not candidates for, need to lose weight before, or prefer a less invasive alternative to bariatric surgery. All the endoscopic procedures have limited availability in Ireland.

Hydrogel

Oral hydrogel therapy obtained FDA approval in 2019 for adults with a BMI of 25·0 kg/m2 or more with or without comorbidities. This treatment involves ingestion of capsules containing a hydrogel matrix that absorbs water in the stomach to form gel pieces that occupy volume, thereby contributing to a feeling of satiety. The hydrogel is broken down in the large intestine and excreted in the faeces. Published data show that, at 24 weeks, mean weight loss was 6·4%. Common adverse effects associated with hydrogel include mild gastrointestinal symptoms such as abdominal discomfort, flatulence, and diarrhoea.

Few endoscopic treatments have shown durable clinical efficacy, and some (eg, tube gastrostomy) have been withdrawn from the market. Endoscopic bariatric therapies in current clinical use include intragastric balloons and endoscopic gastroplasty.

Intragastric balloons

Intragastric balloons reduces food intake by restricting gastric capacity and delaying gastric emptying, temporary, while they are in place. They are usually filled with fluid or air and removed after 6–12 months. Intragastric balloons lead to 15% weight loss. Complications with this procedure occur infrequently and include gastric outlet obstruction, gastric ulceration, and gastric perforation (0·04% to 1·00% of procedures). Intragastric balloons are only useful as a bridge to having another procedure done for people’s health (e.g. knee replacement) and they cannot be used long term for the treatment of obesity.

Endoscopic gastroplasty

Endoscopic gastroplasty reduces gastric capacity by infolding the greater curvature of the stomach with sutures (plication). Endoscopic gastroplasty lead to 13·6% weight loss after 1 year. About 1% of patients have complications, such as perigastric collections, major bleeding, and deep vein thrombosis.

Available bariatric surgery in Ireland

Bariatric surgery is an option for patients with a BMI of 35 kg/m2 or higher who have not responded to other interventions. Bariatric surgery procedures have evolved over the years starting from radical small bowel operations such as the jejunal-ileal bypass in the 1950s, to the gastric bypass in the late 1960s, gastric banding in the 1990s and the vertical sleeve gastrectomy.

The different bariatric procedures currently vary as regards their relative metabolic benefits, as well as surgical risks. The term metabolic surgery is now preferred to describe certain types of surgeries particularly gastric bypass and sleeve gastrectomy to more accurately capture their effects, not only on weight, but also diabetes and cardiometabolic risk. Moreover, this alternative terminology also points to the shift in emphasis it provides towards viewing the health benefits associated with weight loss rather than simply weight loss itself as being the key outcome.

Gastric Band

The Gastric Band (BAND) involves the insertion of an adjustable hallow plastic and silicone ring near the stomach’s upper end, immediately below the gastrooesophageal junction, creating a small pouch and a narrow passage to the remaining part of the stomach. This procedure causes a delayed emptying of food from the pouch and thus a feeling of fullness. The band is adjusted through injections of fluid in a subcutaneous port to change the size of the passage over time causing a reduction of 15% in total body weight.

Vertical Sleeve Gastrectomy

Vertical Sleeve Gastrectomy (VSG) has become increasingly popular due to its relative simplicity and good clinical outcomes. VSG involves the excision of 70-80% of the stomach to make a small stomach that creates a high- pressure chamber which easily generates pressures sufficient to overcome pyloric sphincter tone and thus results in rapid gastric emptying.

Roux-en-Y gastric bypass

The Roux-en-Y gastric bypass (RYGB) is the procedure many consider the gold standard due to its effectiveness in weight loss and weight loss maintenance. Nevertheless, RYGB is technically a more demanding procedure than VSG, but still very safe in good hands. In this procedure, the stomach is transected to generate a small gastric pouch 15 -30 ml in volume, and a lower larger gastric remnant excluded from contact with food. The gastric pouch is then anastomosed to the distal limb of a jejunotomy performed at the mid-jejunum thus forming the alimentary or Roux limb. In the absence of gastric reservoir function or sphincter control this rearrangement allows essentially instantaneous transfer of ingested food to the small intestinal lumen. Gastric, pancreatic and biliary secretions flow undiluted in the biliopancreatic limb proximal to the jejunal transection and are permitted to mix with chyme in a common channel formed by side-to-side anastomosis of the biliopancreatic limb 100150cm distal to the gastro-jejunal anastomosis.

In the short term, weight loss is similar between sleeve gastrectomy and Roux-en-Y gastric bypass (approximately 30% total bodyweight loss at 12 months). In contrast, long-term studies indicate greater weight loss with Roux-en-Y gastric bypass than sleeve gastrectomy (27% vs 23% total bodyweight loss) over 5–7 years’ follow-up. Bariatric surgery also leads to improvement or remission of other obesity-related comorbidities such as, hypertension, obstructive sleep apnoea, musculoskeletal pain, and overall quality of life.

Bariatric surgery has a very favourable risk to benefit profile, but this needs to be evaluated on a case-by-case basis before a decision to proceed is made. Potential complications can be classified as surgical, medical, nutritional, and psychological. These can be prevented or dealt with promptly by an experienced multidisciplinary team.

Take home message

Several options for obesity management are now available, including intensive lifestyle treatment combining nutritional and exercise therapy, pharmacotherapy, endoscopic devices, and bariatric surgery. The treatment option should take the patient’s medical status and wishes into consideration. There is no ‘one size fits all’. Usually, the patients want to be thin and happy. However, a more realistic outcome of all obesity treatments should be aimed at improving health and functionality. The amount of weight loss that needs to be achieved to improve overall health depends on the severity and present complications of obesity. For example, to improve the complication of obesity such as glycaemic control in type 2 diabetes as little as 5% weight loss makes a significant difference, while other complications such as sleep apnoea may require in excess of 10-15% weight loss to reduce the apnoea hypopnoea index below the threshold to require CPAP treatment. Therefore, a personalised decision should be made for each patient.