How Wegovy and other weight loss drugs are changing the obesity treatment landscape

Obesity is a global health problem that affects millions of people and increases the risk of various chronic diseases, such as diabetes, cardiovascular disease, and cancer. According to the World Health Organization (WHO), more than 650 million adults were obese in 2016, and the number is expected to rise in the coming years¹.

Traditionally, obesity treatment has focused on lifestyle interventions, such as diet and exercise, or bariatric surgery for severe cases. However, these approaches are often insufficient or inaccessible for many patients, leaving a gap in the market for effective pharmacological options.

In recent years, several new weight loss drugs have emerged that offer promising results and novel mechanisms of action. One of them is Wegovy, a once-weekly injection developed by Novo Nordisk, a Danish pharmaceutical company. Wegovy is a synthetic version of a gut hormone called glucagon-like peptide-1 (GLP-1), which regulates appetite and blood sugar levels. By mimicking GLP-1, Wegovy reduces hunger and food intake, leading to significant weight loss.

Wegovy was approved by the U.S. Food and Drug Administration (FDA) in June 2021, after showing impressive results in clinical trials. In one study, Wegovy helped patients lose an average of 15% of their body weight over 68 weeks, compared to 2.4% for placebo². Wegovy also improved other health markers, such as blood pressure, cholesterol, and blood sugar levels.

Wegovy is not the only GLP-1-based drug on the market. Novo Nordisk also sells Ozempic, a lower-dose version of Wegovy that is approved for type 2 diabetes and has shown similar weight loss benefits³. Another GLP-1 drug is Saxenda, which is also made by Novo Nordisk and has been available since 2014.

However, Wegovy has some advantages over its competitors. It has a higher dose and a longer half-life than Ozempic and Saxenda, which means it can achieve greater weight loss with fewer injections. It also has fewer side effects, such as nausea and vomiting, than other GLP-1 drugs².

Wegovy is not the only new player in the obesity drug market. Other companies are developing or marketing different types of weight loss drugs that target different pathways or receptors in the body. For example:

• Semaglutide is another GLP-1 drug that is being developed by Zealand Pharma and Boehringer Ingelheim. It is delivered as a daily pill instead of an injection and has shown promising results in phase 2 trials.
• - Liraglutide is a GLP-1 drug that is sold by Novo Nordisk under the brand name Victoza for type 2 diabetes and Saxenda for obesity. It has been shown to reduce the risk of cardiovascular events and slow the progression of kidney disease in diabetic patients.
• - Lorcaserin is a drug that activates serotonin receptors in the brain and reduces appetite. It is sold by Eisai under the brand name Belviq and was approved by the FDA in 2012. However, it was withdrawn from the market in 2020 after a safety study found an increased risk of cancer among users.
• - Phentermine/topiramate is a combination of two drugs that suppress appetite and enhance satiety. It is sold by Vivus under the brand name Qsymia and was approved by the FDA in 2012. It has been shown to cause significant weight loss but also has some serious side effects, such as birth defects, increased heart rate, and cognitive impairment.
• - Naltrexone/bupropion is a combination of two drugs that modulate dopamine and opioid receptors in the brain and reduce cravings and hunger. It is sold by Orexigen under the brand name Contrave and was approved by the FDA in 2014. It has been shown to cause moderate weight loss but also has some common side effects, such as nausea, headache, and insomnia.
• - Orlistat is a drug that inhibits pancreatic lipase, an enzyme that breaks down fat in the intestine. It is sold by Roche under the brand name Xenical for prescription use and by GlaxoSmithKline under the brand name Alli for over-the-counter use. It has been available since 1999 and has been shown to cause modest weight loss but also has some unpleasant side effects, such as oily stools, flatulence, and abdominal pain.

These drugs represent different approaches to obesity treatment that may suit different patients depending on their preferences, medical conditions, and goals. However, none of them are magic pills that can solve obesity without any effort or lifestyle changes.

As Francesco Branca, WHO’s director of nutrition for health and development, told Reuters: “These drugs are not silver bullets” ¹. He added that obesity management requires a comprehensive strategy that includes prevention, education, and behavioural management. Other treatment options include medications, medical devices, and bariatric surgery for patients needing additional interventions. The diagnosis of obesity is based on height and weight, not on a specific biomarker.

The management of obesity requires a comprehensive and individualized approach that considers the patient’s preferences, goals, health status, and readiness to change. The WHO recommends that obesity management should follow a four-step process1:

Assessment: This involves measuring the patient’s body mass index (BMI), waist circumference, and other anthropometric indicators; evaluating the patient’s medical history, comorbidities, medications, and psychosocial factors; and identifying the patient’s motivation, expectations, and barriers to weight management.

Classification: This involves determining the patient’s obesity class based on BMI and waist circumference, and the patient’s risk of obesity-related complications based on comorbidities and other risk factors. The WHO classifies obesity into three classes: class I (BMI 30 – 34.9 kg/m2), class II (BMI 35 – 39.9 kg/m2), and class III (BMI ≥ 40 kg/m2). Waist circumference is used to assess central adiposity and the risk of metabolic syndrome. A waist circumference of ≥ 94 cm for men and ≥ 80 cm for women is considered high risk, while a waist circumference of ≥ 102 cm for men and ≥ 88 cm for women is considered very high risk2.

Intervention: This involves selecting the appropriate intervention based on the patient’s obesity class, risk level, and preferences. The intervention should aim to achieve a realistic and sustainable weight loss of 5 – 15% over 6 – 12 months, which can lead to significant improvements in health outcomes1. The intervention should also address the underlying causes and drivers of obesity, such as genetic, environmental, behavioural, psychological, and social factors. The main types of interventions are:

Lifestyle intervention: This is the first-line therapy for all patients with obesity and involves dietary restriction, increased physical activity, and behavioural modification. The dietary intervention should be tailored to the patient’s preferences, culture, and medical conditions, and should aim to create a moderate energy deficit of 500 – 750 kcal/day. The physical activity intervention should be gradual and progressive, and should aim to achieve at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise per week, as well as resistance training at least twice a week. The behavioural intervention should include self-monitoring, goal setting, problem solving, stimulus control, cognitive restructuring, stress management, relapse prevention, and social support1 .

Pharmacological intervention: This is an adjunct therapy for patients with obesity who have not achieved adequate weight loss or have plateaued with lifestyle intervention alone. It is also indicated for patients with obesity who have comorbidities that may benefit from weight loss. The pharmacological intervention should be prescribed by a physician who is experienced in obesity management and should be combined with lifestyle intervention. The pharmacological intervention should be discontinued if the patient does not achieve at least 5% weight loss after 12 weeks of treatment1 . There are several types of weight loss drugs available or under development that have different mechanisms of action and efficacy profiles. Some examples are:

GLP-1 receptor agonists: These are injectable drugs that mimic the action of GLP-1 hormone and reduce appetite and food intake. They also have beneficial effects on blood glucose control and cardiovascular risk factors. Examples are Wegovy (semaglutide), Ozempic (semaglutide), Saxenda (liraglutide), and Rybelsus (oral semaglutide).

Serotonin receptor agonists: These are oral drugs that activate serotonin receptors in the brain and reduce appetite and food intake. They also have beneficial effects on mood and depression. Examples are Belviq (lorcaserin) and Plenity (gelesis100).

Sympathomimetic agents: These are oral drugs that stimulate the sympathetic nervous system and increase energy expenditure and thermogenesis. They also suppress appetite and food intake. Examples are Qsymia (phentermine/topiramate) and Contrave (naltrexone/bupropion).

Lipase inhibitors: These are oral drugs that inhibit pancreatic lipase enzyme and reduce fat absorption in the intestine. They also induce satiety and reduce food intake. Examples are Xenical (orlistat) and Alli (orlistat).

Bariatric surgery: This is a surgical intervention that alters the anatomy or physiology of the gastrointestinal tract to reduce food intake or nutrient absorption. It is indicated for patients with class II or III obesity who have not achieved adequate weight loss with lifestyle or pharmacological interventions, or who have comorbidities that may benefit from weight loss. It is also indicated for patients with class I obesity who have poorly controlled type 2 diabetes or metabolic syndrome1 . Bariatric surgery requires a multidisciplinary team approach that includes preoperative assessment, perioperative care, :

and long-term follow-up. The bariatric surgery should be selected based on the patient’s characteristics, preferences, and expectations. The main types of bariatric surgery are:

• Roux-en-Y gastric bypass: This is a procedure that creates a small pouch from the upper part of the stomach and connects it to the middle part of the small intestine, bypassing the rest of the stomach and the upper part of the small intestine. This reduces the amount of food that can be eaten and the amount of calories and nutrients that can be absorbed.
• - Sleeve gastrectomy: This is a procedure that removes about 80% of the stomach, leaving a banana-shaped tube that holds less food. This reduces the amount of food that can be eaten and also lowers the levels of ghrelin, a hormone that stimulates hunger.
• - Adjustable gastric band: This is a procedure that places a silicone band around the upper part of the stomach, creating a small pouch that holds less food. The band can be tightened or loosened by injecting or removing saline through a port under the skin. This reduces the amount of food that can be eaten and induces early satiety.
• - Biliopancreatic diversion with duodenal switch: This is a procedure that combines sleeve gastrectomy with a bypass of most of the small intestine, leaving only a short segment for digestion and absorption. This reduces the amount of food that can be eaten and also limits the absorption of calories and nutrients, especially fat.
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• Bariatric surgery has been shown to cause substantial and durable weight loss and to improve or resolve several obesity-related comorbidities, such as type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, and osteoarthritis. Bariatric surgery has also been associated with reduced mortality and improved quality of life. However, bariatric surgery also carries some risks and complications, such as bleeding, infection, leakage, stricture, ulcer, bowel obstruction, malnutrition, dumping syndrome, gallstones, kidney stones, hypoglycemia, and weight regain. Therefore, bariatric surgery should be considered only after careful evaluation and discussion of the benefits and risks with the patient.
• Evaluation: This involves monitoring the patient’s weight loss progress, health outcomes, adherence to lifestyle changes, medication use, side effects, complications, nutritional status, psychological well-being, and satisfaction with the intervention. The evaluation should be done regularly and frequently during the first year after initiating the intervention and then annually thereafter. The evaluation should also include laboratory tests to assess blood glucose control, lipid profile, liver function, kidney function, electrolytes, iron status, vitamin B12 status, :
• and bone mineral density. The evaluation should also involve adjusting the intervention as needed based on the patient’s response, preferences, and goals.
• The management of obesity is a complex and challenging task that requires a multidisciplinary team approach and a long-term commitment from both the patient and the health care provider. The management of obesity should aim to improve not only the patient’s weight and physical health, but also the patient’s psychological and social well-being. The management of obesity should also respect the patient’s dignity, autonomy, and individuality, and avoid stigma, discrimination, and bias.
• : Branca F, Pi-Sunyer X, Astrup A, et al. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000;894:i-xii, 1–253.
• : Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989–1002.
• : Davies MJ, Bergenstal R, Bode B, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA 2015;314:687–699.
• : World Health Organization. Waist circumference and waist-hip ratio: report of a WHO expert consultation. Geneva: World Health Organization; 2008.

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Source: Conversation with Bing, 17/05/2023

(1) Health & Pharma News | Latest Healthcare Stories | Reuters. https://www.reuters.com/business/healthcare-pharmaceuticals/.

(2) Health – BBC News. https://www.bbc.com/news/health.

(3) Disease Outbreak News – World Health Organization (WHO). https://www.who.int/emergencies/disease-outbreak-news.