In less than a decade GLP-1 receptor agonists have transformed the treatment of obesity and made Novo Nordisk Europe’s most valuable company. Diana Spencer explores the current impact and potential future for these drugs.

Originally designed in Scandinavia as a maintenance therapy for type 2 diabetes, GLP-1 receptor agonists are now better known for their extraordinary weight management abilities. This has lifted the drugs to blockbuster status, making the two developers Novo Nordisk and Eli Lilly the most profitable in the world, and causing demand to far outstrip supply.

Here we take a look at the development of these ‘wonder drugs’, their impact on the drugs market in Scandinavia, and what role new products and new indications could play in the future. With an ever-expanding market, a wide range of potential health benefits, and new products on the horizon, it seems highly likely that GLP-1 agonists and their successors will lead the Scandinavian drugs market for many years to come.

GLP-1 receptor agonists: A history

Joel Habener at Massachusetts General Hospital (MGH), Daniel Drucker at the University of Toronto, and Jens Juul Holst at the University of Copenhagen are largely credited with the discovery of glucagon-like peptide-1 agonists (or GLP-1 receptor agonists, incretin mimetics, GLP-1 analogs) in 1986, though it has since come to light that Svetlana Mojsov, also at MGH at the same time, was instrumental in this work.

Then, in 1996, Arne Astrup’s group at the University of Copenhagen and Holst discovered that GLP-1 is a satiety hormone, and this was swifty followed by the invention of liraglutide by Lotte Bjerre Knudsen’s team at Novo Nordisk. Novo was the world’s largest producer of insulin, but had decided to explore new approaches in the early 1990s2. Semaglutide was much more recent, invented by Jesper Lau’s team at Novo Nordisk in 20241.

The US Food and Drug Administration (FDA) approved the first GLP-1 agonist, Eli Lilly and Amylin Pharmaceuticals’ exenatide (Byetta) in 2005. Novo Nordisk’s liraglutide wasn’t approved by the FDA until 2010 to treat type 2 diabetes (under brand name Victoza) and then as a weight management treatment in December 2014 (as Saxenda).

Semaglutide was approved as Ozempic for type 2 diabetes in December 2017, in an oral tablet formulation (Rybelsus) in September 2019, and for weight loss (Wegovy) in June 2021. Lilly’s GLP-1/GIP dual agonist tirzepatide was approved as Mounjaro for type 2 diabetes in May 2022, and then as Zepound for weight management in November 2023.

Arne Astrup explains why there was so much excitement over GLP-1 agonists: “A large body of evidence has demonstrated that complete remission of type 2 diabetes can be achieved by a major weight loss. Until recently, the only effective treatment for obesity was bariatric surgery, and a century of drug development for obesity can be essentially described as a failure until now. GLP-1 analogues have completely changed this bleak therapeutic picture.

“The effects on the brain of GLP-1 analogues go far beyond satiety but may also change food preferences in a healthier direction, but also reduce a person’s drive for alcohol, tobacco and even opioids. Consequently, the potential for this class of drugs is enormous and may be a paradigm shift not only for the management of obesity but also for several other conditions1.”

The obesity drugs market

The scale of the obesity crisis is huge, making this an extremely lucrative market for the pharmaceutical industry. According to the World Health Organization, worldwide adult obesity has more than doubled since 1990, and adolescent obesity has quadrupled. In 2022, 2.5 billion adults (18 years and older) were overweight, and of these, 890 million were living with obesity8.

Sales of branded obesity drugs were $6 billion in 20233. These drugs have had a dramatic impact on the pharmaceuticals market in Scandinavia as a whole, but particularly Denmark, the home of Novo Nordisk. Danmarks Statistik said in February 2024 that the pharmaceutical industry’s gross value added (GVA) increased by more than 50% in 2023, and that its contribution to Denmark’s GDP grew by 1.8% compared to the year before4.

This is primarily driven by sales of Novo Nordisk’s obesity drugs, which have made it not only the leading pharma company in Europe by market capitalisation, but also Europe’s most valuable company (as of March 2023). The company secured net sales of DKK 232.3 million (€31.2 billion) in 2023, up 31% from the year before and 65% from 20214.

The only larger company globally by market capitalisation is Eli Lilly, Novo Nordisk’s main competitor in the obesity market.

The market has expanded at such a phenomenal rate that, since 2022, a surge in demand for GLP-1 agonists, coupled with other issues such as manufacturing capacity constraints, has led to shortages of the drugs across the EU. This was exacerbated by media hype around the drugs as an easy weight loss option. The EMA and the Heads of Medicines Agencies (HMA), through the Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG), issued recommendations to tackle shortages, such as measures to control and optimise the distribution of these medicines, and these have helped to ease the situation6.

The next five years

Morgan Stanley predicts the global market for the blockbuster obesity drugs could increase by more than 15-fold over the next five years to around $105 billion3. Meanwhile GlobalData sees sales reaching up to $142 billion by 2030. The analysts say that Novo Nordisk and Eli Lilly will capture 94% of the total 2030 GLP-1R sales, placing them far ahead of any competitors in this market.

Jasper Morley, Pharma Analyst at GlobalData, comments: “Novo Nordisk and Eli Lilly accounted for nine of the approved GLP-1R products in 2023 and encompassed 99% of the sales. Successful GLP-1R products in 2023 included Novo Nordisk’s Ozempic and Wegovy, which generated $13.9 billion and $4.6 billion, respectively, as well as Eli Lilly’s Trulicity and Mounjaro, which generated $7.1 billion and $5.1 billion.” 

“Despite vast increases in the number of products and competitors expected to enter the GLP-1R market, sales attributed to the 14 companies other than Eli Lilly and Novo Nordisk are forecast to generate only $8.8 billion in 2030, 15 times less than the combined valuation of the two leading companies.”

New indications for GLP-1 agonists

“The obesity drug market is being driven by two key factors. The first is supply. Drugmakers have to keep pace with demand,” says Mark Purcell, Head of Morgan Stanley’s European Pharmaceuticals team. “Second, demand for these medicines could be turbocharged if there’s broadening evidence that these drugs improve outcomes in the hundreds of obesity-related ailments.”

Obesity is responsible for more than half of diabetes cases and can be linked to more than 200 other chronic diseases, including hypertension, heart failure and kidney disease, as well as complications such as sleep apnoea, osteoarthritis and possibly Alzheimer’s disease. In 2023, results of the Phase III SELECT trial revealed that semaglutide 2.4mg could reduce the risk of major adverse cardiovascular events by 20%. Other studies have since shown that patients taking semaglutide were 19% less likely to develop 13 obesity-related cancers,   and had a reduced rates of all-cause death.

“The SELECT trial represents just the tip of the iceberg when it comes to these medicines’ potential to expand into new opportunities,” says Purcell. “Obesity cuts life expectancy by as much as 10 years, depending on age. If the widespread use of weight-loss drugs has a meaningful impact on longevity, there are a variety of ways that they could disrupt healthcare.”

To maintain such a high level of sales in the face of competition and patent expiries, Novo Nordisk is looking to expand into new markets and exploit these new indications. In 2024, in response to the results of the SELECT trial, Wegovy’s approved uses were extended to cardiovascular risk reduction in the US and Europe. Meanwhile, Novo is continuing trials into a range of expanded uses for its drugs, including a Phase III trial into liraglutide for children with obesity9. 

The company also achieved approval in the valuable Chinese market in June 2024, but is at risk of losing out to generic drug-makers there as its China patent is due to expire in 2026, compared to in 2031 in Europe and Japan and in 2032 in the U.S7.

Novo is also looking to expand its obesity pipeline. In March 2024, the company shared Phase I data for amycretin, its novel GLP-1 and amylin co-agonist, which it hopes to launch within this decade. In a meeting with investors, the company shared trial results for the pill version of amycretin, which showed participants lost 13.1% of their weight after 12 weeks, a bigger reduction early on than from Wegovy. In response, shares in Novo Nordisk soared to temporarily surpass Tesla, indicating the level of optimism around these drugs10.

Then in September 2024, Novo announced promising headline results from a Phase IIa clinical trial with monlunabant, a small molecule oral cannabinoid receptor 1 inverse agonist, in people with obesity and metabolic syndrome. “The Phase IIa results indicate the weight-lowering potential of monlunabant and that further work is needed to determine the optimal dosing to balance safety and efficacy,” expands Martin Holst Lange, Executive Vice President and Head of Development at Novo Nordisk. “Obesity is a complex disease with a significant unmet need, and as an oral small molecule having a new mechanism of action, monlunabant is one of the novel projects in our pipeline with the potential of treating obesity.”

Emerging new players

A number of smaller companies are hoping to capture a share of this market in the next five years. Sweden-based Pila Pharma was founded in 2014 by Dorte Gram, formerly part of the obesity research team at Novo Nordisk. This year, the company raised 10 million SEK ($980,320) for a novel Phase IIa obesity-related study of a TRPV1-antagonist.

“When the company was founded 10 years ago, obesity was barely recognised as a disease. But it certainly is today. The industry has traditionally focused on type 2 diabetes, which is also a major market, but in recent years a new market for weight-reducing drugs has emerged,” says Gustav Gram, CEO of Pila Pharma. “If our study shows an effect on obesity, we will be the first and only company to have successfully used this type of molecule – a TRPV1-antagonist – for the treatment of metabolic diseases.”

Another company hoping to follow in Novo’s footsteps is Danish Antag Therapeutics. In October 2024, the FDA accepted an Investigational New Drug (IND) application for Antag Therapeutics’ lead molecule for obesity, AT-7687, a peptide that targets the Glucose-Dependent Insulinotropic Polypeptide (GIP) receptor. In preclinical studies, AT-7687 combined with liraglutide, produced best-in-industry weight loss, which is expected to be largely driven by reductions in fat mass while preserving lean mass. However, the main advantage of the drug’s use as a monotherapy is that it does not cause the gastrointestinal side effects of GLP-1 agonists.

Alexander H Sparre-Ulrich, Chief Executive Officer of Antag Therapeutics, reflects on the market the company is entering: “The fact that Novo Nordisk’s market cap now exceeds Denmark’s annual GDP highlights just how significant GLP-1 drugs have been for the Danish economy. Obesity has only been recognised as a disease for just over 11 years, and Wegovy has been approved for obesity treatment for only three years. Last year, the obesity market was around $24 billion and is projected to exceed $100 billion over the next four years. This market is clearly still in its infancy.

“With their established leadership and decades of cultivating scientific excellence in the metabolic field, I expect Scandinavian companies to continue playing a significant role in the obesity drug market going forward.”

From DDW Volume 26 – Issue 1, Winter 2024/25 Read the digital issue

References:

  1. Astrup A. Reflections on the discovery GLP-1 as a satiety hormone: Implications for obesity therapy and future directions. European Journal of Clinical Nutrition 2024;78:551–556.
  2. Friedman JM. The discovery and development of GLP-1 based drugs that have revolutionized the treatment of obesity. Proc Natl Acad Sci USA 2024;121(39):e2415550121.
  3. https://www.morganstanley.com/ideas/obesity-drugs-market-expanded-opportunity 
  4. https://www.euronews.com/business/2024/02/20/denmarks-gdp-soars-thanks-to-growing-pharma-sector 
  5. https://www.globaldata.com/companies/top-companies-by-sector/healthcare/europe-companies-by-market-cap/
  6. https://www.ema.europa.eu/en/news/eu-actions-tackle-shortages-glp-1-receptor-agonists
  7. https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisk-says-semaglutide-approved-long-term-weight-management-china-2024-06-25/ 
  8. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
  9. https://www.nejm.org/doi/10.1056/NEJMoa2407379 
  10. https://www.reuters.com/business/healthcare-pharmaceuticals/novo-nordisk-hopes-launch-experimental-obesity-drug-within-this-decade-2024-03-08/ 

About the author:

Diana SpencerDiana Spencer is Senior Digital Content Editor at DDW. She has 20 years’ experience in both print and digital editorial roles for B2B publications dedicated to the life sciences sector, including medical and pharmaceutical industry journals/magazines.