Belgian Researchers Unveil Dual Strategy for Type 1 Diabetes
Belgian researchers from the Vrije Universiteit Brussel (VUB), UZ Brussel, and KU Leuven have demonstrated that a combined treatment targeting both the immune system and the insulin-producing beta cells of the pancreas can significantly slow the progression of type 1 diabetes. In preclinical trials using a mouse model, the combination therapy reduced diabetes incidence from 77 percent in untreated subjects to just 38 percent, offering new hope for millions of patients worldwide.
The findings, published in the leading scientific journal Diabetologia, represent a paradigm shift in how researchers understand and approach the autoimmune disease.
A New Understanding of the Disease
Type 1 diabetes occurs when the immune system mistakenly attacks and destroys the beta cells in the pancreas — the body’s “insulin factories.” Without functioning beta cells, patients become dependent on lifelong insulin injections or insulin pumps. Approximately 4 out of 1,000 people in Flanders live with the condition.
For years, scientific research focused exclusively on immunotherapy — calming the immune system to prevent it from attacking beta cells. The best-known immunotherapy, Teplizumab, was recently approved in Europe and can delay disease onset by an average of about two years in high-risk individuals.
However, as the VUB press release explains, this new research reveals that beta cells are not passive victims. Under stress, beta cells display molecular “flags” that make them more visible to the immune system, creating a vicious cycle of attack and destruction.
Two Targets, One Treatment
The experimental therapy combines two components with complementary mechanisms:
- Anti-CD3 — an immunotherapy that reprograms the immune system to inhibit the autoimmune attack on beta cells
- GLP1-E2 — an experimental compound that delivers protective oestrogen (estradiol) specifically to beta cells, using GLP-1 as a targeted delivery mechanism
The GLP-1 molecule is the same class of drug used in popular weight-loss and diabetes medications like Ozempic. In this research, GLP-1 acts as a “specialized delivery service,” carrying estradiol precisely to beta cells while avoiding the systemic side effects that would occur if oestrogen were given broadly — such as increased risk of blood clots, hormone-sensitive cancers, or breast development in men.
Striking Results in Preclinical Models
In the study, prediabetic NOD mice were treated with low-dose anti-CD3, GLP1-E2, or a combination of both. The results were clear:
- Untreated mice: 77 percent developed diabetes by 30 weeks
- Anti-CD3 alone: 66 percent developed diabetes
- GLP1-E2 alone: 61 percent developed diabetes
- Combination therapy: Only 38 percent developed diabetes
Furthermore, the onset of diabetes was significantly delayed, and part of the protective effect persisted even after GLP1-E2 treatment was discontinued.
“These results support the idea that type 1 diabetes is not solely a disease of the immune system, but also of vulnerable beta cells,” said Prof. Dr. Nico De Leu, an endocrinologist at UZ Brussel and VUB who co-leads the Beta Cell Neogenesis (BENE) lab. “By tackling both autoimmunity and the stress and vulnerability of beta cells, we observed significantly stronger protection in this model than with a single treatment alone.”
Implications for Future Treatment
Prof. Dr. Willem Staels, a paediatric endocrinologist at UZ Brussel and VUB and co-leader of the BENE lab, emphasized that this is not yet a therapy for patients. “But this study provides important evidence that we may need to look beyond immunotherapy alone,” he said. “By also actively protecting the beta cells, future treatments may become not only more potent but also more sustainable.”
The treatment is designed for pre-symptomatic individuals — those identified as high-risk before clinical diagnosis. This is critical because by the time type 1 diabetes is clinically diagnosed, approximately 70 percent of beta cell function has already been lost.
Belgium already screens first-degree relatives of people with type 1 diabetes, who have approximately 10 to 15 times higher risk of developing the condition themselves. The research team, which also includes first author Laure Degroote, now aims to move toward human clinical trials.
What’s Next
While the results are promising, the researchers caution that this is a preclinical study conducted in a mouse model, and results cannot be directly extrapolated to humans. Further studies are needed to determine safety and efficacy in patients.
If confirmed in human trials, this combination approach could fundamentally change how type 1 diabetes is managed — shifting from treatment after diagnosis to prevention before onset. The targeted delivery mechanism using GLP-1 as a carrier could also have applications for other diseases where localized hormone therapy is needed.
More information about the research group’s work is available at the BENE lab website.