Denosumab: Another Reason to Screen for T1D 

 The City of Hope is conducting phase I/II trials on individuals with fully established T1D’s (one to five years from diagnosis).

Denosumab is currently used to treat osteoporosis and bone tumors under the brand name Prolia®. Developed by the biotech company Amgen, Prolia helps stop the development of bone-removing cells before they can reach and damage the bone. Doctors typically give patients with osteoporosis a subcutaneous injection every six months.

Researchers hope to use this same technique to treat type 1 diabetes (T1D), an autoimmune condition in which the body attacks the insulin-producing islet cells in the pancreas.

If the drug can stop rogue cells from damaging bone density, they’re banking it can do the same with beta cells. The FDA-approved denosumab could protect the cells from the autoimmune attack, including transplanted stem cell-derived beta cells.

Preventative Treatment for T1D

In addition to trials with established T1D patients, City of Hope is also exploring denosumab use as a preventative therapy for individuals who test positive for islet autoantibodies. Islet autoantibodies attack the insulin-producing beta cells in the pancreas. Scientists can spot these antibodies in the blood to determine if a person may develop type 1 diabetes.

By researching denosumab in the early stages of T1D, the City of Hope seeks to stop beta cell destruction before the damage occurs.

Denosumab Overview

How it Works

In type 1 patients, denosumab may inhibit and block a protein called RANKL (Receptor Activator of Nuclear Factor Kapp-B Ligand). RANKL is responsible for both bone breakdown and the destruction of pancreatic beta cells.

Denosumab binds to RANKL, protects the beta cells (and implanted stem cells) from future attacks, and preserves the cell function, ideally slowing down the progression of T1D.

Key Points about Denosumab and T1D

• Denosumab may increase the number of insulin-producing beta cells in the pancreas.
• Denosumab may improve the existing beta cell function.
• The drug may also reduce inflammation around the beta cells.

When applied, denosumab could protect beta cells from future immune damage.

Promising Therapeutic Approaches to Treat T1D

Cell Regeneration

The objection of cell regeneration for type 1 diabetes is to restore the insulin-producing pancreatic beta cells by stimulating existing cells to replicate or convert other pancreatic cells into beta cells.

• Islet Cell Transplants. Islet cells from a deceased donor are transplanted into the liver of a patient with T1D. Lantidra is an FDA-approved cell regeneration therapy that uses cells made from deceased donors.
• Endogenous Regeneration. Existing pancreatic beta cells are stimulated to replicate and convert into new beta cells.
• Stem Cell Therapy. Stem cells can adapt into multiple cell types.

Immune System Modification

Immune system modification involves reprogramming the immune system to stop attacking the pancreas. Beta cell destruction can occur over months or years, resulting in a lack of insulin.

New immunotherapy technologies could treat T1D by training the immune system to accept the existing and newly transplanted beta cells.

Drug Repurposing to Cure T1D

Denosumab received a $2.23 million grant from Breakthrough T1D (formerly JDRF), the global organization that works on therapies for treatments that control autoimmunity and preserve or regrow beta cells. The Breakthrough T1Ds research program also supports using the blood pressure medication Verapamil as a possible treatment for type 1 diabetes.

Denosumab Side Effects

While this study is optimistic, the research is still in the early stages of assessing its safety and efficacy. The drug has caused a number of adverse effects, ranging from mild to severe.

These complications include bone pain, skin problems and bladder infections. Other consequences may involve high blood pressure, diarrhea, nausea and vomiting. The more serious complications are low blood calcium levels, thigh bone fractures, and lung infections.

Cell Protection is Key in Trial

The Arthur Riggs Diabetes and Metabolism Research Institute is coordinating the current phase I/II trial in collaboration with the Center for Diabetes and Metabolic Diseases at Indiana University and the University of Alabama at Birmingham Comprehensive Diabetes Center.

Phase I/II trial is recruiting 45 participants with established T1D, one to five years after diagnosis. Denosumab is distributed to individuals via subcutaneous injection once every three months. The end goal is to boost beta cell function. With the early trials concluding in April 2026, it still has a way to go.

Denosumab Pros and Cons

The pros are that the drug is already on the market for osteoporosis and could be easily adapted for T1D patients. The challenge is the drug’s potential side effects, such as bone pain, depleted calcium and increased risk of infection.

However, if denosumab can stop the autoimmune attack, it’s extremely promising. If proven effective, the drug could also protect stem cell-derived beta cells. More research is needed to gauge the risks and possible side effects.

Hopefully, they’ll keep the focus on established T1Ds and preventative therapy for the early stages of T1D–a win for all.