Jan Jezek leads research and development for the proprietary protein stabilization technologies of Arecor Therapeutics’ Arestat platform and their application to commercial therapeutic products.
Credit: Jan Jezek, Arecor Therapeutics
Over the past decade, few areas of medicine have captured both scientific and public attention as dramatically as GLP-1 (glucagon-like peptide-1)-based therapies. First developed for diabetes, GLP-1 agonists have since proven highly effective for obesity and metabolic disease, opening the door to much broader applications.
What is especially striking is how far their potential now appears to reach. Beyond weight and glucose control, studies are uncovering benefits across cardiovascular and kidney disease, neurodegeneration, and even addiction — raising the question of what GLP-1 agonists can’t do. While the full picture is still emerging, the breadth of these effects underscores why expectations for this drug class have soared.
Their rise reflects more than just clinical efficacy: It highlights shifting attitudes toward obesity as a treatable medical condition, new capabilities in drug design and delivery, and unprecedented market momentum. To better understand how the field is evolving — and where it might go next — DDN spoke with Jan Jezek, Chief Scientific Officer at Arecor Therapeutics, about the scientific challenges, delivery innovations, and future opportunities surrounding GLP-1 therapies.
How has the landscape of GLP-1 therapies evolved since the launch of semaglutide (Ozempic/Wegovy)?
The GLP-1 space really took off with semaglutide: first as Ozempic for type 2 diabetes in 2017, then as Wegovy for obesity in 2021. While GLP-1 drugs have existed since the early 2000s, semaglutide revealed their potential beyond diabetes, particularly in obesity, where past treatments were often found inadequate.
Novo Nordisk was the trailblazer, followed closely by Eli Lilly. They solved two major challenges: optimal binding to the GLP-1 receptor and particularly extended circulating half-life, making it both effective and reasonably tolerable. These scientific breakthroughs coincided with obesity becoming a top global health issue in the past 15–20 years, driving a perfect storm for adoption.
Technology has also accelerated the field. Artificial intelligence (AI), computational modelling, and advanced drug design allow companies to explore new molecules more efficiently. There are over a hundred obesity products now in clinical development, many of them GLP-1-based, driven by strong medical need, novel drug discovery tools, and financial opportunity. In my view, semaglutide hasn’t just succeeded, it has reset expectations for obesity and metabolic disease treatment.
What are the main challenges companies face when trying to improve efficacy or safety in this competitive class?
You could say that the field has become the victim of its own success.
– Jan Jezek, Chief Scientific Officer at Arecor Therapeutics
This is a serious challenge, and you could say that the field has become the victim of its own success. Drug delivery now presents a major hurdle, but at the same time, a great opportunity for product differentiation. Injections remain the most effective method, providing consistent systemic dosing, but most patients would prefer a pill. This is why oral formulations are such a focus area for the leaders in the pack, Novo and Lilly, as well as newer entrants like Kailera, Metsera, and Verdiva. Oral delivery will not only improve patient compliance and broaden access, but it can also cut the manufacturing bill and reduce environmental impact through the elimination of injectable device disposal.
The difficulty is that peptides like semaglutide are large, complex, and sensitive molecules that are prone to degradation and are not easily absorbed by the gastrointestinal (GI) tract. Formulation can improve both stability and absorption, but even with the most advanced formulation, the only oral GLP-1 available today achieves roughly one percent absorption, and uptake varies widely between patients, making consistent dosing a challenge.
Developing oral delivery without compromising safety or efficacy is the next major frontier in this sector. Success here could improve outcomes and expand access for patients who need these therapies. Oral delivery is not just convenient, it’s critical for the future of next-generation GLP-1 and similar therapeutic products.
Why have GLP-1 receptors historically been difficult to target with small molecules, and what has changed to make oral versions possible now?
Targeting any receptor with small molecules is inherently challenging because of basic biology. Receptors are typically protein-based and embedded in cell membranes. Nature designed peptides as the natural “keys” to activate them. This makes peptides the obvious choice when mimicking receptor interactions.
The challenge is that peptides are difficult to deliver orally; they get broken down in the digestive system, which is why injectable delivery has been standard to date. GLP-1 receptors are also relatively large, requiring larger peptide molecules for efficient, specific binding. Small molecules simply can’t make enough contact, which is why oral GLP-1 agonists were out of reach for decades.
However, innovation in computational drug design and formulation technology is changing this. Modelling complex interactions helps design better molecules, while advanced formulations protect therapeutics through digestion and improve their systemic uptake. Oral semaglutide demonstrates this possibility, even with only about one percent absorption.
Beyond weight loss and glucose control, how do you see GLP-1 agonists being leveraged to treat other conditions, such as cardiovascular disease, chronic kidney disease, sleep apnea, or osteoarthritis?
GLP-1 agonists are already being used beyond weight loss and glucose control. For example, both semaglutide and tirzepatide, in addition to their primary indications for type 2 diabetes and obesity, have demonstrated cardiovascular benefits. Semaglutide has also now been approved by the FDA and the UK’s Medicines and Healthcare products Regulatory Agency to reduce cardiovascular risk. This expansion makes sense when you consider how interconnected the body’s systems are; you can’t isolate an individual system, since disruption in one system always impacts others due to their highly integrated nature.
The receptors for GLP-1s can be found in different organs: in the pancreas, regulating insulin; in the brain, influencing appetite and behavior; throughout the GI tract; and in the heart and kidneys. Administering a GLP-1 agonist affects multiple organs simultaneously, explaining secondary benefits like reduced appetite, cardiovascular improvements, and kidney protection.
The effects also go well beyond weight loss. One of the widely recognized effects of GLP-1 is the reduction of inflammation by suppressing the release of various inflammatory cytokines. Most chronic diseases are inflammatory in nature, and the systemic anti-inflammatory properties of GLP-1, combined with the abundance of GLP-1 receptors throughout the body, open the door to addressing cardiovascular disease, kidney disease, sleep apnea, osteoarthritis, and more, making the wider potential for this range of therapeutics very exciting.
Are there opportunities to use GLP-1 medicines for addiction or other behavioral conditions?
Absolutely. There’s growing interest in using GLP-1 drugs for addiction. Studies have been reported showing that semaglutide can reduce alcohol cravings and heavy drinking days; animal studies suggest similar effects on drug-seeking and relapse. At the European Association for the Study of Diabetes, there was also an update on Novo’s studies showing that Wegovy reduced food noise, as well as boosting mental well-being.
Again, it makes sense biologically since GLP-1 receptors are in the brain’s reward and appetite centers, and they are acting on the brain’s craving pathways. That said, clinical evidence is still limited, and it is strongest for alcohol abuse. It will be interesting to see if GLP-1 impacts the craving for opioids or stimulants. The potential is real, but we need bigger, longer trials before this area becomes a clinical reality.
Could the pleiotropic effects of GLP-1 drugs on multiple organ systems change how we think about treating obesity-related comorbidities as a whole?
GLP-1 drugs are already changing how we treat obesity-related comorbidities. Just look at Ozempic, which now carries cardiovascular indications on top of weight and glucose control. This tells us these medicines are acting systemically, not just in one place. To me, it comes back to seeing health holistically. You can’t completely separate obesity, diabetes, cardiovascular disease, or kidney disease — they’re all linked.
As mentioned above, a common denominator is inflammation. Chronic conditions create a background level of cytokines and inflammatory signals that affect multiple organs, which explains why obesity raises the risk of so many other diseases.
GLP-1 agonists fit right into this picture. Their receptors are scattered across the body, so when you target them, you’re influencing both metabolism and inflammatory pathways at once. The result is that we need to rethink how we treat diseases — not just managing conditions separately but addressing them together.
How do you see AI and computational tools helping to identify new targets for weight loss or metabolic diseases beyond GLP-1?
AI and computational tools have advanced enormously, and I see their biggest impact in designing safer and more efficacious drugs for the right targets. They’re helping us — not just to identify new receptors in biology, but particularly to create molecules that bind effectively, maximize safety, and boost potency.
The really exciting shift is that these tools now extend beyond drug discovery; they’re transforming formulation and delivery too. In the past, drug design and delivery were separate stages, but now companies can think about both upfront. This is critical for treating weight loss and metabolic disease, where success depends not only on the target but how it’s delivered.
How might next-generation GLP-1 therapies be combined with other treatments to maximize benefits across metabolic and cardiovascular disease?
The next generation of obesity therapies are already involving combinations, either as two separate molecules or by combining two or more targeting moieties in one molecule. Eli Lilly’s tirzepatide (Mounjaro and Zepbound) is a GIP (glucose-dependent insulinotropic polypeptide)/GLP-1 dual agonist that is demonstrating excellent weight loss, type 2 diabetes management, as well as cardiovascular protection. Novo’s CagriSema program is another good example of a combination drug (cagrilintide + semaglutide).
Early studies are encouraging, but it’s technically hard to combine peptides in a single formulation, since each has different stability requirements. Formulation creativity will be key here. Developing innovative formulations of therapeutic peptides to achieve convenient dosage forms is a key focus for our team and we have an excellent track record in this field.
However, it’s not just about combinations of different drugs and molecules; there are other areas to consider to ensure long-term benefits across other diseases. First, weight loss drugs should always be paired with lifestyle improvements — better diet, exercise, and protein intake. One known risk with GLP-1s is muscle loss, so at a minimum, resistance training and a protein-rich diet should be encouraged. In the longer term, you could combine a GLP-1 with medication preventing muscle loss, or even more fundamentally, design the weight loss medications to be directed fully to adipose tissue while minimizing muscle loss. Not an easy task, but I am sure we will see progress in this area.
With dual and triple agonists under development, how do we determine the optimal balance of hormones in combination therapies to maximize efficacy while minimizing side effects?
Finding the right balance within the population of dual or triple agonists in development is going to be one of the toughest challenges. If you think of all the possible mechanisms, across GLP-1, GIP, amylin, and even cannabinoid receptors, you get a giant Venn diagram of overlapping options. The aim will be to investigate which combinations are the most synergistic.
The “optimal balance” isn’t going to be a single answer. It will come down to developing a strategy, then choosing what we think are the right targets, designing stable molecules, running the studies, and having the discipline to stop if it’s not working.
– Jan Jezek, Chief Scientific Officer at Arecor Therapeutics
Computational and AI tools can help model those interactions, but in the end, it’s down to real-life biology within clinical trials. There’s a limit to how much can be derisked in advance, and there will always be different effects due to people’s individuality. Also, with up to 10 different pathways that could influence obesity and cardiovascular disease, the permutations are huge.
The “optimal balance” isn’t going to be a single answer. It will come down to developing a strategy, then choosing what we think are the right targets, designing stable molecules, running the studies, and having the discipline to stop if it’s not working. These are the fundamentals of drug discovery and development.
This interview has been condensed and edited for clarity.
