Denosumab: A Potential Practical Cure for T1D?

January 23, 2025

Denosumab for Type 1 Diabetes, a phase I/II clinical trial coordinated by the City of Hope Medical Center, could be a potential Practical Cure along the Cell Regeneration and Immune System Modification pathways. Denosumab is an FDA-approved medication for osteoporosis and bone-related diseases that is theorized to positively affect beta cell health, encouraging proliferation and cell protection.

The following provides an overview of Denosumab and its implications for T1D.
 

What Is It?

Denosumab is a drug currently FDA approved to treat osteoporosis under the brand name Prolia. It was developed and marketed by the biotech company Amgen. 

Denosumab is a monoclonal antibody that targets a protein called RANKL (Receptor Activator of Nuclear Factor Kapp-B Ligand) to stop the development of ‘bad’ cells that break down bone.

The drug is presented in a liquid form and is injected under the skin, usually in the upper arm, thigh, or stomach. For osteoporosis, it is typically administered once every six months.
 

Denosumab for T1D

City of Hope researchers are leading a phase I/II trial to see if Denosumab can stop the autoimmune attack in people with T1D. They believe the same mechanism that halts bone degradation might also stop the autoimmune attack on islet cells. By inhibiting RANKL, Denosumab aims to reduce inflammation, protect beta cells from immune damage, and preserve and improve their function.

If proven effective and safe, this might provide protection for any type of islet cell that is transplanted, including stem cell-derived beta cells. As a result, it has the potential to become a Practical Cure for T1D. It is a new addition to our current list under the Cell Regeneration and Immune System Modification pathways.
 

The Current Trial

The trial is being coordinated by the City of Hope Medical Center in Duarte, California. It is currently recruiting forty-five individuals with established T1D, one to five years post diagnosis. The primary objective is C-peptide growth, a hormone demonstrating the presence of insulin production.

Denosumab will be given as a subcutaneous injection once every three months. Participants will be closely monitored for changes in beta cell function, as measured by C-peptide levels and improvements in HbA1c.

Prudence Buxton, Director of Science and Clinical Communications at the City of Hope, confirmed, “The end goal of the Denosumab treatment is to protect, expand and improve beta cell function in individuals with type 1 diabetes. In line with the JDCA’s definition of a Practical Cure, the hope is that Denosumab will significantly boost beta cell function, increasing endogenous insulin secretion and thereby allowing achievement of tight glucose control with minimal restriction and effort.”

The trial is led by Fouad Kandeel, MD, PhD, and Rupangi Vasavada, PhD, at the City of Hope Medical Center. Funded by a $2.23 million grant from Breakthrough T1D, the study is a collaboration with research centers at Indiana University and the University of Alabama at Birmingham.
 

Advantages and Challenges

There are several advantages and challenges to Denosumab achieving a fully realized Practical Cure, namely accessibility, cell protection, and efficacy.

Advantages

Since Denosumab is already commercially available, its adoption as a therapy for T1D would be streamlined if proven effective. Denosumab also holds the potential to be widely accessible as the drug is not tailored to each patient and could be produced at scale.

Challenges

Denosumab is already marketed for other conditions, but potential side effects have been reported, such as low calcium, increased infection risk, and bone pain. Side effects impacting bone health and immune function must be carefully managed, even if present in the minority. It remains unknown if there are unique risks to someone with T1D.

In addition, translating efficacy in other diseases into a long-term treatment for T1D is not a guarantee. Larger trials and long-term data will be essential in determining drug safety, efficacy, and the ability to protect new beta cell growth—all of which will take time.

Lastly, there is some risk of mission drift. In our correspondence with City of Hope, they indicated that the drug may also be studied as a preventive therapy for individuals with positive islet autoantibodies, an indicator used to predict T1D onset. It is unclear if this could later shift focus away from people with fully established T1D.
 

Next Steps

The trial is expected to conclude in April 2026, with results posted in the following months.

If successful, future trials are anticipated to evaluate efficacy in individuals with a diagnosis greater than five years, and in higher numbers. The JDCA will continue to monitor the progress of this trial and provide updates on its outcomes, next steps, and broader implications for Practical Cure research.
 
 

Appendix: Additional Trial Details
Denosumab for Type 1 Diabetes is a phase I/II trial testing whether injections of Denosumab will protect, expand, and improve beta cell function.

Purpose: To evaluate the safety and efficacy of Denosumab in protecting, expanding, and improving beta cell function in individuals with T1D (1–5 years post diagnosis).
Dosing: 60 mg subcutaneous injection of Denosumab or placebo administered every three months for one year.
Estimated Enrollment: 45 participants.
Locations: City of Hope Medical Center, Indiana University, and the University of Alabama at Birmingham.
Estimated Study Completion Date: April 2026.