28-29 GLP-1 New balancing

The landscape of weight loss management is rapidly shifting beyond the initial dominance of Ozempic and Wegovy, leading to the emergence of next-generation treatments.

Among these new weight loss treatments is retatrutide, developed by Eli Lilly. Retatrutide has been positioned as a potential ‘new wave’ therapy with initial clinical data suggesting superior weight loss results compared with Wegovy.

The growing popularity of GLP-1 receptor agonists will have a significant impact on the pharmaceutical sector with commercial and IP considerations becoming just as important as clinical efficacy.

Retatrutide, a synthetic 39-amino acid peptide, is an investigational weight loss medication, which is currently undergoing phase 3 clinical trials.

Unlike semaglutide (Ozempic/Wegovy), which targets a single receptor (GLP-1), or tirzepatide (Mounjaro/Zepbound), a dual agonist for GLP-1 and GIP receptors, retatrutide goes one step further and acts as a triple agonist targeting GLP-1, GIP and glucagon receptors.

Retatrutide therefore builds on existing incretin-based therapies and signals a shift in obesity drug development by simultaneously targeting multiple hormone receptors.

This ‘triple G’ effect is thought to lead to a more comprehensive and powerful metabolic response, resulting in higher weight loss, improved metabolic outcomes and increased energy expenditure.

Initial results from retatrutide’s first phase 3 trial (TRIUMPH-4) showed an average weight loss of 28.7% at 68 weeks on the highest dose (12 mg).

In comparison, results from Wegovy’s high dose (semaglutide 7.2 mg) phase 3b STEP UP trial achieved 20.7% weight loss at 72 weeks.

The emergence of next-generation drug candidates such as retatrutide demonstrates that there is still an appetite to drive innovation within this increasingly crowded space.

This is not surprising when the global market size for GLP-1 analogues in 2024 was valued at $54.8 billion and is estimated to reach $268.4 billion by 2030.

With such high stakes at play, and with more companies hoping to capitalise on the success of recent obesity drugs, a key strategy for market leaders such as Novo Nordisk and Eli Lilly to retain dominance and competitive advantage will, in part, rely on having a strong IP and patent portfolio surrounding these therapies.

Although patent protection for semaglutide in the US, UK and many parts of Europe is likely to last until 2031 and beyond, this is not the case for all jurisdictions.

Core patents for semaglutide have already expired or lapsed in countries such as India, Canada, China, Brazil, South Africa and Turkey.

This means that in the coming years we are likely to see a surge of generic competition for earlier generation weight loss drugs such as Wegovy. Therefore, having a robust IP strategy in place to protect the pipeline of potential drugs will be crucial for any company.

For retatrutide, Eli Lilly’s core patents covering the compound appear to have been filed in 2018. Any granted patents directed to retatrutide will likely provide Eli Lilly with exclusivity at least until 2038, blocking potential generic entry for this new peptide.

There is no doubt that the GLP-1 landscape has significantly evolved in the last few years, from the early days of single hormone agonists like semaglutide to multi-hormone agonists of today such as tirzepatide and retatrutide.

But what advancements are likely to shape the future of obesity drugs?

For existing drugs, we are likely to see developments designed for easier and more convenient administration. Initial forms of Wegovy and retatrutide were formulated as once-weekly injections.

However, we are already seeing the emergence of oral dosage forms such as oral semaglutide and orforglipron (Foundayo), which come as daily oral pills providing alternatives to weekly injections.

We could also see more combination therapies being developed to reduce side effect profiles and achieve more efficient or synergistic results than can be accomplished with monotherapies.

CagriSema is a fixed-dose combination of semaglutide and cagrilintide (a long-acting amylin receptor agonist). A new 68-week trial found that weekly injections with CagriSema resulted in greater weight loss (up to 14.2%) compared with 10.2% for semaglutide (Wegovy).

Another combination therapy comprising semaglutide and bimagrumab, an investigational antibody targeting type II activin receptors, has been reported to provide significant fat loss while preserving lean mass.

Beyond efficacy alone, as the obesity treatment market continues to grow and competition intensifies, there will likely be an increasing focus on accessibility, affordability and long-term patient adherence.

As healthcare systems continue to evaluate the financial impact of obesity-related conditions, there will be increasing pressure on pharmaceutical companies to demonstrate both clinical effectiveness and wider economic and societal benefits.

This may include evidence relating to type 2 diabetes prevention, cardiovascular health and reductions in healthcare costs associated with obesity-related illnesses.

Additionally, regulatory scrutiny surrounding safety, side effect management and appropriate patient use is expected to increase as treatments become more widely adopted. Greater pressure may also fall on manufacturers to address supply chain capacity and ensure reliable global availability as demand for obesity therapies continues to grow.

For more progressive companies, we may see more AI-driven drug R&D being utilised, which could shorten the preclinical phase significantly and lead to more rapid target identification, virtual screening and toxicity predictions.

The integration of AI in R&D, coupled with synthetic biological systems that mimic metabolic processes and the monitoring of digital biomarkers, could also allow weight management to become more effective, accessible and personalised.

Retatrutide and the ‘triple G’ effect

Patent protection and market exclusivity

The next generation of obesity therapies

Challenges facing the obesity treatment market