An interview with Professor Thomas Forst, Chief Medical Officer, hVIVO
Obesity research is a rapidly developing field, and few areas have advanced faster than incretin-based medicines such as GLP-1 receptor agonists.
Professor Thomas Forst, Chief Medical Officer of hVIVO, speaks about what this means for patients, medication developers, and the larger cardiometabolic environment in this interview. He examines the true causes of obesity-related disease, the potential and limitations of GLP-1s, and how a more nuanced understanding of fat biology is altering the field.
Looking at the current obesity landscape, where do you see the greatest unmet need?
TF: We have discovered that obesity is more than just excess weight. It is a complicated, progressive condition with major medical implications.
Obese people are at a higher risk of developing type 2 diabetes, cardiovascular disease, heart failure, sleep apnea, and some malignancies. These complications, rather than the number on the scale, drive morbidity and mortality.
As a result, there is a two-fold need: medicines that effectively address the underlying metabolic abnormalities, and techniques that lessen the burden of these comorbidities. That is where the field has made significant development in the recent decade.
Image Credit: hVIVO
GLP-1 receptor agonists have become critical to that development. What makes them so effective?
TF: GLP-1s were first discovered as therapies for type 2 diabetes, and their weight-loss properties were practically a bonus. Over time, we have discovered that these medications do far more than only reduce hunger and body weight. They boost overall metabolic health.
Clinical investigations have revealed fewer cardiovascular events, better heart failure outcomes, benefits for renal disease, and positive effects on conditions such as sleep apnea. Importantly, these benefits apply to persons who are obese even if they do not have diabetes.
So, while the public debate frequently focuses on weight loss, the actual narrative is that GLP-1s help address the metabolic abnormalities that make obesity such a risky condition.
You have stated previously that "not all fat is equal." What exactly do you mean by that?
TF: Body weight and BMI are imprecise measurements. They reveal very little about the biological processes that cause harm.
The main issue is where the fat is stored and how it acts. Ectopic fat occurs when fat develops in locations where it should not be, such as the liver, heart, pancreas, or skeletal muscle. This sort of fat is metabolically active in the worst possible way: it causes inflammation, secretes toxic adipokines, and disturbs normal organ function.
Ectopic fat is a far more reliable predictor of cardiometabolic risk than BMI. Measures such as waist circumference, waist-to-height ratio, and waist-to-hip ratio often reveal more about a patient's risk profile than just weight.
When we talk about treating obesity, we truly mean lowering the dysfunctional fat and the inflammatory environment it causes.
Given the complexity, are GLP-1s a complete solution?
TF: They are effective tools, but they are not the complete solution - and they were never intended to be. GLP-1s are part of a larger family of incretin-based medicines, and the field is already exploring dual and triple agonists, as well as oral small-molecule compounds that target multiple pathways simultaneously.
These novel drugs may provide even greater metabolic benefits, but none of them supersede the basics. Lifestyle change is still important. Physical exercise and diet remain vital, especially since weight loss, whether drug-induced or not, can lead to muscle mass loss. Muscle preservation is crucial to long-term health. As a result, it is usually a combination of medicine and lifestyle, rather than either alone.
What should drug developers keep in mind as this therapeutic landscape expands?
TF: Science is advancing rapidly, but the basic biology has not changed. Obesity is a metabolic condition with numerous long-term repercussions, and the most effective treatments will address the entire spectrum of these complications, not just weight.
hVIVO has spent years working in this field, assisting sponsors in understanding how these medications behave in early-phase studies and in designing programs that capture the relevant signals. The more we understand about fat biology and metabolic dysregulation, the more precise and effective these treatments may be.
Any final thoughts for clinicians or researchers watching this space?
TF: We are approaching a new age in obesity treatment. GLP-1s opened the door, but they are merely the beginning. As more advanced incretin-based medicines become available, we will be able to treat not only obesity but also the complete range of disorders that it causes.
Even with these improvements, we must not lose sight of the fundamentals. Medication works best in conjunction with lifestyle changes that promote metabolic health. That combination, science and behavior, will produce the best results for patients.
About Professor Thomas Forst
Professor Thomas Andreas Forst is a board-certified physician in internal medicine and endocrinology with more than 30 years of experience in
cardiometabolic research. He began his scientific career at the German Diabetes Research Institute and later held academic and clinical roles at the Johannes Gutenberg University Mainz, where he continues to contribute to medical training. Thomas has held senior positions at Eli Lilly, the Institute for Clinical Research and Development, and the Profil Institute Mainz, and has served as CMO at Clinical Research Services Germany. He has contributed to more than 300 clinical trials across obesity, metabolic disease, diabetes, lipid disorders, and cardiovascular disease, and is an active member of major diabetes associations. He has authored over 300 peer-reviewed publications and serves as Associate Editor of Endocrinology, Diabetes & Metabolism.