What if the miracle molecule that changed obesity treatment isn’t the final answer?

For years, therapeutic options were limited, while investments were modest. But thanks to the Glucagon-like peptide 1 (GLP-1) receptor antagonist, which gave birth to Semaglutide (Ozempic and Wegovy) and Tirzepatide (Zepbound), a paradigm shift in obesity treatment is taking on a new course.

The GLP-1 receptor antagonist is a peptide hormone initially intended to treat Type 2 diabetes. Further research has shown promising effects not only in blood sugar regulation but also in appetite and digestion. 

However, while it has the potential to aid weight loss and open new doors for research and increased funding, GLP-1 still has its limitations, which may include cost, adverse effects, and supply issues.

That means experts still have to rethink how they can discover a true game-changer to battle global obesity, and fast.    

Obesity: A Continuously Growing Global Challenge

By 2030, over 1.13 billion people, or approximately 13.3% of the entire global population, will be living with obesity. Another hard pill to swallow is the World Health Organization’s (WHO) recent report of how 390 million children aged five to 19 were overweight last year. 

Add these numbers up, and we’re all looking towards a global crisis that could continue to increase by 115% from 2010 to the next 10 years. Failure to address the problem could also cost the global economy an estimated $4.2 trillion annually or 3% of the global GDP within the same period. And the most unfortunate part in all of this is that obesity is rising fastest in low to middle-income countries with the weakest health systems.

So yes, while obesity is everyone’s health and economic problem, we can’t just solve it with the same tools we’ve used in the past. Moving forward, the most important innovations to come won’t be just about what we treat, but rather how we discover and develop the treatments.

What the GLP-1 receptor antagonist treatments got right (and didn’t)

Let’s give credit where it is due: GLP-1 receptor agonists Semaglutide and Tirzepatide didn’t just open new opportunities for research in our global battle against obesity. It also raised the public’s awareness while allowing the scientific community to put more weight (pun intended) in its perception when it comes to treatment. 

The results speak for themselves. One of the most extensive clinical trials on Semaglutide reported that patients lost up to 10% of their body weight in four years. Soon enough, market enthusiasm followed, with the global GLP-1 market projected at $100 billion by 2030. 

Of course, enthusiasm is not the same as sustainability. Such therapies faced several barriers, including how a monthly prescription could cost a patient anywhere between $936 and $1,340.

Most GLP-1 receptor antagonist therapies also require weekly injections, which is another challenging issue in patient adherence. 

Studies also show that 50% of users experienced gastrointestinal symptoms such as nausea, vomiting, and diarrhea. On the other hand, over 181,000 adverse events were reported between 2004 and 2023 due to GLP-1 receptor agonists, including over 8,000 psychiatric cases. 

There is also the proliferation of counterfeit versions of GLP-1 receptor antagonists, particularly fake Ozempic, which have led to 1,000 adverse event cases during the first quarter of this year.  

Barriers such as these prevent the GLP-1 receptor antagonist from being a population-scale solution, even forcing big-name pharma Pfizer to withdraw its oral GLP-1 candidate earlier this year due to tolerability issues. And even with promising results from companies like Eli Lilly and Novo Nordisk, manufacturing woes still persist.

With the rapid increase of obesity worldwide, we need fresh alternatives that are easier to take, faster to produce, and less expensive for the people who need them most.

Rethinking the Biology

This is why we must look beyond the GLP-1 receptor antagonist and apply what we’ve learned from it to something new. One fresh alternative lies in re-examining a previously underutilized target: the Amylin receptor. By having Artificial Intelligence (AI), robotics, and protein science work together efficiently, we can go after Amylin more confidently.

Small molecules are perfect for obesity solutions because of their potential for oral delivery, lower costs, and broader patient access. Amylin, being a hormone secreted alongside insulin, can reduce cravings and keep patients feeling full, while also regulating blood sugar. In other words, it’s the kind of target we need and want.

Of course, there’s no discounting the complexities of the Amylin receptor. It’s a structural complex, which historically was a difficult target with traditional small-molecule drugs. Still, Amylin’s biology is strong, as evidenced by Pramlintide, an injectable Amylin analog approved way back in 2005. Its low commercial uptake was eventually limited by frequent dosing and reports of hypoglycemia cases.   

Today, thanks to new tech and tools, we have the opportunity to revisit the Amylin potential. This time, we look towards smarter molecule discovery through a smarter process rather than injectables to address pressing global concerns.

The Bigger Shift Towards System Engineering

At the rate generative AI, robotics, and protein science are developing, it becomes easier to predict how molecules behave. More importantly, it’s now possible to design new ones from scratch and optimize them against multiple properties in parallel. 

For such a complex receptor as Amylin, such development matters enormously. While traditional drug discovery takes at least 12 years on average from discovery to market, AI and robotics can reduce the timeframe to at least 18 months. Using these technologies and tools allows for fast iteration and replaces much guesswork with data-driven engineering.

Combining cutting-edge protein science and automation results in fewer necessities for trial and error, higher reliability in testing, and more concrete insights. Smarter optimization also results in higher hit quality and scalable workflows for difficult targets like G protein-coupled receptors (GPCRs) and transporters. 

Finally, the possibility of producing pills in lieu of injectables makes it more viable for low-resource regions worldwide. Small molecules also mean lower production costs, no cold storage required, and are easier to prescribe, ship, and store for better patient adherence and availability.  

With an integrated approach in system engineering, it doesn’t mean we would be skipping vital steps for the sake of streamlining processes. What it means is we can better test our hypotheses faster, optimize more efficiently, and then learn from every iteration. 

What Comes After the GLP-1 Receptor Antagonist?

This current shift could likely be the magic pill in our fight against global obesity. With a new generation of therapies that are built on better biological targets and powered by better discovery engines, Amylin receptors are back on the table in a big way.

More than that, it improves our processes in how we design, test, and validate new medicines with greater speed, accuracy, and ultimately, broader reach. In this scenario, while traditional drug discovery can be likened to searching a needle in a haystack, AI, robotics, and protein science become your much-needed magnet.

We have outgrown the idea that success takes decades, and the Amylin receptor is a promising test case that can unlock multiple pathways to previously undruggable targets.  

About the Author

Yann Gaston-Mathe has extensive work experience in various roles within the pharmaceutical and biotechnology industries. Yann is the Co-founder and CEO of Iktos since October 2016.

Origianl Creator: Yann Gaston-Mathe
Original Link: https://justainews.com/industries/healthcare-and-medical/rethinking-obesity-drugs-ai-beyond-glp-1/
Originally Posted: Fri, 05 Dec 2025 11:42:13 +0000