How EndoCompass Charts the Future of Diabetes and Obesity Research
Imagine your body's metabolism as a complex, finely-tuned engine—constantly processing energy, managing hormones, and maintaining balance. Now imagine that engine spiraling out of control, leading to weight gain, energy crashes, and potentially devastating health consequences.
This isn't a hypothetical scenario for millions of Europeans; it's their daily reality. Diabetes, obesity, and related metabolic disorders represent one of the most pressing public health challenges of our era, affecting millions across Europe and placing a significant burden on healthcare systems 5 .
Yet, despite the staggering prevalence of these conditions, research into their endocrine underpinnings remains critically underfunded and fragmented, accounting for less than 4% of Horizon 2020's biomedical and health research budget 2 5 6 .
Enter EndoCompass—a groundbreaking initiative launched in October 2025 by the European Society of Endocrinology (ESE) and the European Society for Paediatric Endocrinology (ESPE). Developed over two years through the collaboration of 228 clinical and scientific experts from across Europe, along with patient advocacy groups and partner societies, this ambitious research roadmap aims to serve as a compass for endocrine research for the next decade 2 5 6 .
We hope it can inspire all those working in endocrinology to ensure that research focuses on the highest priority questions.
EndoCompass represents a paradigm shift in how we approach metabolic research. Rather than maintaining fragmented, isolated efforts, this initiative marks the first comprehensive, coordinated strategy to address the growing crisis of metabolic diseases across Europe.
The project emerged from a stark realization: while endocrine diseases affect millions, there exists a persistent gap between their societal impact and their research prioritization in European Union funding programs 1 4 .
Endocrine research received less than 4% of Horizon 2020 biomedical and health research funding, despite the significant impact of metabolic diseases.
The roadmap was developed through meticulous analysis and extensive expert consultation involving 228 specialists across Europe.
EndoCompass has been a huge collaborative effort, bringing together more than 220 scientists, clinicians and patient representatives from across Europe. It reflects a shared recognition of the urgent need to align our research priorities and work together to shape the future of endocrine science and deliver better care and outcomes for patients.
The EndoCompass roadmap for diabetes, obesity, and metabolism focuses on several transformative research areas that promise to reshape our understanding and treatment of these complex conditions.
Our genetic makeup plays a crucial role in metabolic health, but it's not just about the genes we inherit—it's about how they're regulated. Epigenetic modifications can be influenced by factors like diet, stress, and environmental exposures.
EndoCompass prioritizes unraveling these complex genetic and epigenetic networks to identify novel therapeutic targets and enable personalized treatment approaches .
The brain constantly communicates with metabolic tissues through a complex network of hormonal signals and neural pathways. Disruptions in this communication system can lead to dysregulated appetite, impaired glucose sensing, and faulty energy expenditure.
Research in this area focuses on understanding how the brain integrates signals from fat tissue, the pancreas, and the gut to coordinate metabolic balance .
We cannot understand the rising rates of metabolic disorders without considering the environmental context in which they occur. Endocrine-disrupting chemicals found in plastics, pesticides, and industrial pollutants can interfere with hormonal signaling.
EndoCompass emphasizes research into how these external factors interact with our biology to either promote or protect against metabolic dysfunction 5 .
| Research Area | Key Questions | Potential Impact |
|---|---|---|
| Genetic/Epigenetic Factors | How do genetic variations and epigenetic modifications influence metabolic disease risk? | Personalized prevention strategies and targeted therapies |
| Brain-Periphery Communication | How does the brain regulate appetite, glucose homeostasis, and energy expenditure? | New treatments for obesity that work with the body's natural regulation systems |
| Environmental Influences | Which environmental chemicals disrupt metabolic function, and how can we mitigate their effects? | Public health policies to reduce exposure and prevent disease |
The EndoCompass roadmap doesn't just stop at understanding metabolic diseases—it charts a course toward revolutionary treatments that could transform patient care.
Monogenic forms of diabetes, which result from single-gene mutations, represent unique opportunities for targeted interventions. Unlike type 2 diabetes with its complex interplay of multiple genes and environmental factors, monogenic diabetes can potentially be addressed through gene therapies or highly specific pharmacological approaches that correct the underlying genetic defect .
The remarkable success of incretin-based therapies (such as GLP-1 receptor agonists) has validated the importance of gut hormones in metabolic regulation. The next generation of these therapies includes dual receptor agonists that simultaneously target multiple hormonal pathways, potentially offering enhanced efficacy for both weight loss and glucose control .
The trillions of bacteria inhabiting our gastrointestinal tract—collectively known as the gut microbiome—play a surprising role in metabolic health. These microbes influence everything from how we extract energy from food to how we respond to medications.
EndoCompass prioritizes comprehensive microbiome analysis to identify specific bacterial strains that promote metabolic health and develop interventions like probiotics or microbiota transplants to restore healthy microbial ecosystems .
Despite advances in pharmacological treatments, behavioral interventions remain foundational to managing metabolic diseases. The roadmap calls for developing more effective strategies that acknowledge the complex psychological, social, and environmental factors driving behaviors related to diet and physical activity.
This includes leveraging digital health technologies to provide personalized, real-time support .
To understand how EndoCompass priorities translate into actual research, let's examine a hypothetical but representative experiment investigating a novel dual receptor agonist for obesity and type 2 diabetes.
This 12-month, randomized, double-blind, placebo-controlled trial involved 480 adults with obesity and type 2 diabetes across 15 European medical centers.
HbA1c, fasting glucose, oral glucose tolerance tests
DEXA scans for fat and lean mass distribution
24-hour blood pressure, ECG, lipid panels
Standardized questionnaires assessing physical function, energy levels, and psychological well-being
Stool samples collected at baseline, 3 months, and 12 months
Plasma samples analyzed for novel protein and metabolic biomarkers
The experimental results demonstrated the superior efficacy of the dual receptor agonist compared to existing therapies. Particularly noteworthy was the significant improvement in glucose control accompanied by substantial weight reduction—a dual benefit that addresses two key aspects of metabolic syndrome.
| Treatment Group | Weight Change (%) | HbA1c Reduction (%) | Systolic BP Reduction (mm Hg) | Quality of Life Improvement (%) |
|---|---|---|---|---|
| Dual Agonist | -14.2 ± 2.1 | -1.8 ± 0.3 | -8.2 ± 3.1 | +32.5 ± 6.4 |
| GLP-1 Agonist | -8.7 ± 1.8 | -1.2 ± 0.3 | -5.1 ± 2.8 | +18.3 ± 5.2 |
| Lifestyle Only | -4.3 ± 1.2 | -0.5 ± 0.2 | -2.3 ± 1.9 | +12.1 ± 4.7 |
| Placebo | -0.8 ± 0.9 | -0.1 ± 0.1 | -0.9 ± 1.5 | +2.3 ± 3.8 |
Beyond these clinical parameters, the study revealed fascinating insights into the mechanisms of action. Microbiome analysis showed a significant shift toward bacterial species associated with leanness and improved metabolic health in the dual agonist group. Additionally, the research team identified three novel protein biomarkers that predicted treatment response with 88% accuracy—a finding that could eventually help match the right patients with the right therapies.
| Bacterial Group | Change with Dual Agonist | Correlation with Weight Loss | Correlation with HbA1c Improvement |
|---|---|---|---|
| Bacteroidetes/Firmicutes Ratio | +42% | r = 0.72 | r = 0.68 |
| Akkermansia muciniphila | +285% | r = 0.81 | r = 0.75 |
| Faecalibacterium prausnitzii | +156% | r = 0.69 | r = 0.64 |
| Bifidobacterium spp. | +98% | r = 0.58 | r = 0.61 |
This experiment exemplifies the multidimensional approach championed by EndoCompass—moving beyond simply measuring weight loss or glucose levels to understanding the underlying physiological changes and identifying biomarkers that can guide future treatment personalization.
Modern metabolic research relies on a sophisticated array of reagents and technologies. Here are some essential tools driving innovation in the field:
Function/Application: Simultaneously activate multiple hormonal pathways (e.g., GLP-1/GIP)
Research Context: Investigating enhanced efficacy for weight loss and glucose control through multi-target approaches
Function/Application: Microfluidic devices containing living human tissues that emulate organ functionality
Research Context: Studying human metabolism without animal models; allows testing of drug effects on miniature engineered human livers, pancreases, or fat tissue
Function/Application: Precisely modifies specific DNA sequences in cellular and animal models
Research Context: Creating models of monogenic diabetes; identifying and validating new therapeutic targets by manipulating candidate genes
Function/Application: Measures gene expression in individual cells rather than bulk tissue
Research Context: Mapping cellular heterogeneity in metabolic tissues; identifying new cell subtypes in pancreas, fat, and liver that may contribute to disease
Function/Application: Allows tracking of nutrient metabolism through the body
Research Context: Quantifying how nutrients are processed in real-time in humans; studying fuel utilization differences between lean and obese individuals
Function/Application: Mice engineered with human genes, cells, or tissues
Research Context: Studying human-specific aspects of metabolism and testing therapies in more relevant biological systems
The EndoCompass Research Roadmap represents more than just a document—it embodies a collective commitment to addressing some of Europe's most pervasive health challenges through coordinated, strategic science.
By aligning research priorities across institutions, disciplines, and national borders, this initiative promises to accelerate the pace of discovery in metabolic health. As Professor Martin Fassnacht notes, "Ultimately, this is about improving hormone health and tackling some of Europe's most pressing and under-recognised health challenges" 2 .
The roadmap's emphasis on understanding fundamental mechanisms while simultaneously developing practical therapeutic innovations creates a powerful feedback loop—each discovery informing the next, each answered question revealing new avenues for exploration. From deciphering the genetic blueprint of metabolic diseases to harnessing the power of gut hormones and microbes, the research priorities outlined for diabetes, obesity, and metabolism offer hope for millions affected by these conditions.
Perhaps most importantly, EndoCompass represents a shift in perspective—recognizing that metabolic diseases are not simply failures of individual willpower but complex disorders of biological systems that require sophisticated, multidisciplinary solutions. As this comprehensive roadmap guides research investments and priorities over the coming decade, we can anticipate not just incremental advances but potentially transformative breakthroughs in how we prevent, treat, and ultimately conquer the metabolic disorders that burden our society.
Now, the journey toward a metabolically healthier Europe begins.