Besides the extraordinary success of GLP-1 agonists, the recent groundbreaking developments within obesity treatment have also led to obesity being viewed as a chronic biological disease.

The World Obesity Federation estimates that 1.1 billion people over the age of five are obese today, and 1.6 billion are overweight. The prevalence of obesity in the U.S. has grown from 30.5% in 1999–2000 to 41.9% in the period of 2017–2020, according to the Centers for Disease Control and Prevention (CDC). Obesity is also on the rise in the Nordic region with Finland in the lead. According to the Finnish Institute for Health and Welfare, of young adults under 30, 19% of women and 17% of men are obese. In the adults-over-30 age group, 28% of women and 26% of men are obese. Almost one in two men and women have abdominal obesity. These extra kilos entail increased risk of severe health conditions like type 2 diabetes, heart diseases, and even certain cancers, and the global cost of treating obesity-related complications is expected to be USD 1.2 trillion by 2025.

According to the Finnish Institute for Health and Welfare, of young adults under 30, 19% of women and 17% of men are obese. In the adults-over-30 age group, 28% of women and 26% of men are obese.”

Up until recently the road to weight-loss for people suffering from obesity was long and hard, and often impossible. The pharmacological management of obesity has included amphetamines, thyroid hormones, dinitrophenol, and various drug combinations that were withdrawn due to serious adverse effects shortly after regulatory approval (Müller et al., Nature Review, 2021). Agents as diverse as mitochondrial uncouplers, sympathomimetics, serotonergic agonists, lipase inhibitors, cannabinoid receptor antagonists, and a growing family of gastrointestinal-derived peptides chemically optimized for pharmaceutical use have also been investigated. Many of these approaches, conclude Müller et al., have had a common inability to achieve placebo-adjusted mean weight loss greater than 10% of initial body weight when chronically administered at tolerable doses. If greater weight loss is achieved, it has typically been accompanied with serious acute or chronic adverse effects.

The discovery

So what is so great about these GLP-1 agonists? Briefly put, they mimic the glucagon-like peptide-1 (GLP-1) satiety hormones in our bodies, which lower blood sugar and curb appetite. GLP-1 was first discovered at the University of Copenhagen in 1986 by professor Jens Juul Holst and his colleagues, and since then scientists and companies have developed treatments for glucose regulation, mainly in diabetes.

This year, the FDA also approved a label expansion for Wegovy for the indication of reducing the risk of major adverse cardiovascular events including cardiovascular death, non-fatal heart attack (myocardial infarction), or non-fatal stroke in adults who are either overweight or obese and have an established cardiovascular disease.”

A once-weekly injection of Novo Nordisk’s semaglutide (brand name Wegovy) was FDA approved in June 2021 after a Phase III trial showed that the participants lost 15% of their body weight after 16 months of treatment. In early 2022 it was approved in the UK and the EU as well. In the 2000s the FDA began approving drugs that mimicked GLP-1 for type 2 diabetes treatments (including Novo Nordisk’s Ozempic, which is the same drug as Wegovy but in a different dose), but scientists had noticed their trial participants also lost weight. So they began to trial these drugs for obesity. Today Wegovy is  an approved weight-loss drug for adults who have obesity, as well as people with a body mass index (BMI) of at least 27 who also have a weight-related condition, such as high blood pressure or high cholesterol. This year, the FDA also approved a label expansion for Wegovy for the indication of reducing the risk of major adverse cardiovascular events including cardiovascular death, non-fatal heart attack (myocardial infarction), or non-fatal stroke in adults who are either overweight or obese and have an established cardiovascular disease.

The new market

The GLP-1 market has so far been dominated by Novo Nordisk’s Ozempic and Wegovy and Eli Lilly and Company’s Zepbound and Mounjaro, and according to Chris Schott, a Senior Analyst at J.P. Morgan, the obesity market will largely be a duopoly between these two companies (The increase in appetite for obesity drugs, J.P. Morgan, 2023). However, J.P. Morgan also predicts the emergence of new biotech firms seeking to enter this drug race, for example exploring how certain medications work in tandem with GLP-1s.

A chronic biological disease

There is no doubt that these new drugs have been a real game-changer within obesity treatment. The newest generations of GLP-1s and combos have led to approximately15–25% weight loss on average, well above prior generations of products. They can obviously save lives and reduce healthcare costs, but they are also changing the narrative on obesity. The condition is starting to be viewed as a chronic biological disease and outside of the patients’ control through lifestyle changes alone.

While demand could continue to outstrip supply for the next several years, we do see these issues resolving in the longer term with more plants coming online and more competitive oral options becoming available.”

However, there are also challenges, including financial and practical ones. For example, patients need to be on these drugs for the long term and often cannot stop taking them. Data from a Novo-funded study in April 2022 showed that patients regained two-thirds of their lost weight one year after discontinuing the use of the drug. Another obstacle is providing access to those who really need them. The drugs have been in short supply at pharmacies worldwide and those who really need injections cannot get them. “While demand could continue to outstrip supply for the next several years, we do see these issues resolving in the longer term with more plants coming online and more competitive oral options becoming available,” predicts Chris Schott in the J.P. Morgan report.

A pill on the way

And now, there is a race towards FDA approval of an equally effective oral medicine. Oral weight loss drugs may signal a more affordable and easier alternative to drugs that require injections. Novo Nordisk’s Rybelsus, a once-daily oral version of semaglutide, was FDA approved in 2019 for type 2 diabetes management. Last year, the company released the results from a 68-week trial with 667 adults who are either obese or overweight with one or more comorbidity. On average, participants lost 15.1% of their body weight after 68 weeks compared to 2.4% of body weight from those on the placebo.

The study acknowledged that the side effects were comparable to the semaglutide injections, with mainly mild to moderate gastrointestinal adverse events (like nausea or diarrhea) being the most common side effect. So it is just a matter of time …