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Effective first-line therapy for treatment of obesity

Obesity, a chronic metabolic disorder, has emerged as a global health epidemic. Its prevalence has increased steadily over the past decades, reaching alarming proportions and posing a significant burden on healthcare systems worldwide.

Obesity is associated with a myriad of adverse health consequences, including diabetes, high blood pressure, cardiovascular diseases, sleep apnoea, osteoarthritis and certain types of cancer.

In recent years, glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed as anti-diabetes agents, have emerged as a promising class of anti-obesity medications. While it is not the first GLP-1 agonist on the market, Semaglutide, commercialised under the names of Ozempic and Wegovy, is the flagship drug in this class. At present, Semaglutide is approved for use in obesity management, in both diabetic and non-diabetic patients.

How do GLP-1 receptor agonists work?

GLP-1 is a naturally occurring hormone secreted by the gastrointestinal tract in response to food intake. It plays a crucial role in regulating glucose metabolism and appetite.

Semaglutide and the likes mimic the actions of GLP-1, exerting a range of metabolic effects that contribute to weight loss.

These effects include:

1, Enhanced insulin secretion: from the pancreas, promoting glucose uptake by different body cells and lowering blood sugar levels (“the incretin effect”)

2, Suppressed glucagon secretion: from the pancreas, preventing excessive glucose release, mostly by the liver

3, Delayed gastric emptying: GLP-1 agonists slow down the movement of food from the stomach into the small intestine, prolonging satiety and reducing appetite

4, Central appetite regulation: GLP-1 receptors are expressed in areas of the brain involved in appetite control. Activation of these receptors by Semaglutide suppresses appetite and promotes satiety

5, Peripheral energy expenditure: by stimulating metabolic processes in fat cells and muscles

6, Modulation of gut bacteria or “microbiota”: these agents may influence weight loss by altering the composition of gut bacteria, which play a role in regulating energy balance and appetite

Clinical efficacy of GLP-1 receptor agonists

Clinical trials have demonstrated the efficacy of GLP-1 receptor agonists in promoting weight loss in individuals with obesity.

Studies have shown that these medications can lead to significant reductions in body weight, ranging from 5 per cent to 15 per cent, compared to placebo or other anti-obesity drugs.

In addition to their weight-loss effects, GLP-1 receptor agonists have also demonstrated in multiple international trials encompassing more than 50,000 patients, a myriad of favourable effects on other obesity-related comorbidities, with a whopping risk reduction of 20 per cent to 35 per cent, such as:

1, Lowering blood sugar, given that they are also anti-diabetes medications

2, Controlling blood pressure

3, Improving cholesterol profile

4, Decreasing stroke risk

5, Slowing kidney damage

6, Protecting the cardiovascular system

7, Reducing inflammation, a common pathway to many chronic diseases

How tolerated are these agents?

GLP-1 receptor agonists are well-tolerated medications. The most common side-effects include gastrointestinal disturbances, such as nausea, vomiting, and diarrhoea. These side-effects are typically mild and transient, and often resolve with continued treatment.

In contrast, some other anti-obesity medications have been associated with more serious side-effects, including cardiovascular risks, which have led to their withdrawal from the market.

How about their long-term efficacy?

Studies have shown that individuals who maintain treatment with GLP-1RAs can sustain their weight loss over extended periods. Once Semaglutide is stopped, the patient could put back on, within a year or so, up to 75 per cent of their weight loss.

This should not come as a surprise, since obesity, like hypertension, hyperlipidaemia and diabetes, is a chronic disease and requires long-term treatment similar to these other conditions. As an example, any discontinuation of anti-hypertension medications could result, within just a few days, in an unacceptable rise in blood pressure levels.

How about their cost efficiency?

While Semaglutide and Semaglutide-like agents are quite expensive and a strategy to reduce their prices is urgently needed, many cost-efficiency analyses conducted in multiple countries have shown a significant intermediate to long-term healthcare costs reduction with their use, since obesity and its associated comorbidities are quite prevalent and their current financial burden is enormous. Hence, an effective anti-obesity strategy using these agents would trim down a sizeable portion of these expenditures by mitigating, slowing or preventing some of the chronic conditions listed earlier in this article.

How about Mounjaro or Zepbound?

Tirzepatide, commercialised under the above two names is also a GLP-1 receptor agonist, but has additional mechanisms of action that gives it more weight losing power, of about 20 per cent, equivalent to the effect of a gastric reduction surgery! It has also been extensively studied, and is now approved by multiple health agencies around the word, including the FDA, as a novel anti-obesity drug.

In summary, GLP-1 RAs have emerged as an effective first-line therapy for the treatment of obesity. Their superior efficacy, favourable safety profile and comprehensive health benefits make them a marvellous breakthrough in modern medicine that could change the whole landscape of obesity and chronic diseases management.

Joe Yammine, MD is a consultant cardiologist at the Bermuda Hospitals Board. Nisrine Atieh, MD is an American-board certified paediatrician and obesity medicine specialist

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Published November 28, 2023 at 7:59 am (Updated November 29, 2023 at 8:06 am)

Effective first-line therapy for treatment of obesity

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