Part 2 Trial of Mixture Remedy for Kind 1 Diabetes Exhibits Promise


Compared to the placebo group, patients with diabetes who received 54 weeks of treatment had higher levels of endogenous insulin secretion with no safety concerns noted.

A recent study examining a candidate combination therapy for adults with recent type 1 diabetes (T1D) showed promising results and offers a potential way to treat the autoimmune disease without making the body susceptible to infectious diseases.

The randomized, double-blind, placebo-controlled study was funded by Novo Nordisk. The results were published in The Lancet Diabetes and Endocrinology. The therapeutic candidate combined anti-interleukin (IL) -21 antibodies with liraglutide, a commonly prescribed drug for diabetes. This approach is based on research from Dr. Matthias von Herrath, professor at the La Jolla Institute for Immunology.

“This is the first large study for combination therapy and the data suggest it is of value to patients,” von Herrath said in the press release.

T1D occurs when the body’s own T cells mistakenly target insulin-producing beta cells in the pancreas. When these beta cells die, the body loses its ability to regulate glucose levels, which can eventually lead to severe organ damage and death. This poses a challenge in treating type 1 diabetes, as therapies that target system-wide T-cell responses can also affect the immune system’s ability to fight real threats like viruses and bacteria, according to the study.

The researchers therefore focused on uncovering the molecular triggers of T1D. Your work has shown some ways to modulate parts of the immune system without suppressing the function of the entire immune system. In 2012, the researchers published a study showing the role of the IL-21 receptor in the uptake of harmful T cells by the pancreas. Follow-up studies showed that an anti-IL-21 antibody can disrupt this signal and possibly protect the pancreas from attack.

In particular, because the anti-IL-21 antibody appears to affect only one group of T cells, von Herrath and his colleagues believed that the antibody could help treat T1D without depressing the entire immune system. A preclinical study published in 2017 showed the effects of combination therapy consisting of an anti-IL-21 monoclonal antibody combined with liraglutide, which has been shown to protect beta cell function. The study showed that this combination could reverse T1D in a mouse model, according to the researchers.

For the new study, von Herrath and his colleagues tested the combination therapy in a randomized, placebo-controlled double-dummy-double-blind phase 2 study with parallel groups. Compared to the placebo group, patients who received the 54 weeks of treatment had higher endogenous insulin secretion. No safety concerns were identified.

The researchers followed the study participants for 26 weeks after stopping treatment and found that the effects subsided during that time. They also found no lasting adverse changes in the immune system, although they did state that the combination therapy needs to be evaluated in a Phase 3 clinical trial for long-term safety and effectiveness.


LJI research leads to a promising combination therapy for type 1 diabetes [news release]. La Jolly Institute for Immunology; March 9, 2021. Accessed March 11, 2021.