Belgian Combo Therapy Halves Type 1 Diabetes Risk in Study

Belgian researchers have demonstrated that a combination therapy targeting both the immune system and the insulin-producing beta cells of the pancreas can dramatically slow the progression of type 1 diabetes. In a preclinical study published in the journal Diabetologia, scientists from Vrije Universiteit Brussel (VUB), UZ Brussel, and KU Leuven showed that the dual approach reduced diabetes incidence in prediabetic mice from 77% to just 38% — a reduction of more than half.

A Paradigm Shift in Understanding the Disease

For decades, type 1 diabetes has been understood primarily as an autoimmune disorder in which the body’s immune system mistakenly attacks and destroys the beta cells responsible for producing insulin. Consequently, most therapeutic efforts have focused on immunotherapy — calming the immune system to slow the attack.

However, the Belgian team’s research reveals a more complex picture. “Those beta cells turn out not to be just passive victims,” said Prof. Dr. Nico De Leu, an endocrinologist at UZ Brussel and VUB who co-led the study, as reported by Het Laatste Nieuws. The research shows that stressed beta cells actively contribute to their own destruction by displaying molecular “flags” that make them more visible to the immune system, creating a vicious cycle of attack and vulnerability.

Two Targets, One Treatment

The combination therapy developed by the researchers addresses both sides of this equation. The first component, anti-CD3 immunotherapy (similar to the recently approved drug Teplizumab), calms the autoimmune attack by reprogramming the immune system. The second component, an experimental compound called GLP1-E2, delivers the protective hormone estradiol specifically to beta cells using GLP-1 — the same molecule that forms the basis of drugs like Ozempic — as a targeted delivery vehicle.

This targeted delivery is crucial, as systemic estrogen therapy carries risks including thrombosis and hormone-sensitive cancers. By using GLP-1 as a “specialized delivery service,” the researchers ensure the protective hormone reaches only the beta cells, while the GLP-1 molecule itself also stimulates insulin production.

Results That Exceeded Expectations

The study, published in Diabetologia (Vol. 69, pp. 2307–2322), tracked four groups of prediabetic NOD mice — a standard model for type 1 diabetes research. At 30 weeks of age, 77% of untreated mice had developed diabetes. Treatment with anti-CD3 alone reduced this to 66%, while GLP1-E2 alone brought it to 61%. But the combination therapy slashed the rate to 38%, with disease onset delayed by 5 to 6 weeks. Notably, part of the protective effect persisted even after treatment was discontinued.

According to a VUB press release, Prof. De Leu stated: “These results support the idea that type 1 diabetes is not solely a disease of the immune system, but also of vulnerable beta cells. By tackling both autoimmunity and the stress and vulnerability of beta cells, we observed significantly stronger protection.”

Hope for Prevention, Not Just Treatment

The researchers emphasize that this is not yet a treatment available to patients. The results were obtained in a mouse model and require confirmation in human clinical trials, which typically take years. However, the study opens a promising new avenue for preventing the disease in people at high risk.

Crucially, the therapy targets the pre-symptomatic stage of type 1 diabetes, before clinical diagnosis. “By the time type 1 diabetes is diagnosed, on average 70% of beta cell function has already been lost,” explained Prof. De Leu. “We focus on the stage before clinical diagnosis, when there are no symptoms yet.”

Belgium already screens first-degree relatives of type 1 diabetes patients, who face a 10 to 15 times higher risk of developing the disease. If human trials confirm the findings, early screening combined with preventive therapy could fundamentally change how type 1 diabetes is managed.

What Comes Next

Prof. Dr. Willem Staels, a pediatric endocrinologist at UZ Brussel and VUB who co-led the research at the BENE Lab, struck a cautious but hopeful tone: “For patients, this is not yet a new therapy. But this study provides important evidence that we may need to look beyond immunotherapy alone. By also actively protecting the beta cells, future treatments may become not only more potent but also more sustainable.”

The next step is to test the combination therapy in human clinical trials. If successful, this dual approach could represent a fundamental shift in the treatment of type 1 diabetes — moving from managing symptoms after diagnosis to preventing the disease before it takes hold.

For the approximately 40,000 people living with type 1 diabetes in Belgium and the 9.5 million worldwide, that prospect offers a powerful new reason for hope.