Can This Triple-Combo Oral Therapy Restore Insulin Production?

The Israeli mini biotechnology company says that combining two existing drugs with a unique version of a common supplement can dramatically restore insulin production in people with type 1 diabetes.

Levicure’s triple combo oral therapy is already considered to be extremely safe as it includes two drugs approved by the US Food and Drug Administration (FDA) and the well-known supplement.

Find out about Levicure’s history, research and future clinical trials.

What is Levicure’s Triple Combo Oral Therapy?

Levicure’s treatment combines two drugs and one supplement, apparently combining insulin production in people with type 1 diabetes, especially those diagnosed with this condition.

Treatment is the following combination:

• DPP4 inhibitors, Common Type 2 Diabetes
• Proton pump inhibitors (PPIs), Drugs of severe acid reflux
• Unique version Gamma aminobutyric acid (GABA), Commonly used supplements to treat anxiety

None of these drugs can restore insulin production alone in people with type 1 diabetes. However, when combined, triple combo therapy works to reverse the progression of type 1 diabetes and restore insulin production by targeting both immune and metabolic problems.

According to Levicure, the combined effects can block beta cells’ destruction, suppress autoimmunity, and restore beta cell function.

DPP-4 inhibitors

DPP-4 inhibitors, usually prescribed in patients with type 2 diabetes, help protect the body’s production of GLP-1 hormone. This is a hormone mimicked by the hit diabetes drugs semaglutide (Ozenpic) and tilzepatide (Moujaro). DPP-4 inhibitors prevent the breakdown of natural GLP-1 hormones. GLP-1 hormone helps regulate appetite, metabolism, natural insulin production, sensitivity to insulin, how quickly it breaks down food, and how much glucose the liver produces.

DPP-4 has been studied in people with T1D, but the results were not sufficient to guarantee regular prescriptions.

Proton pump inhibitors

Proton pump inhibitors (PPIs), which are usually prescribed in people with chronic acid reflux, reduce the amount of acids produced by the stomach.

PPI also increases gastrin levels. This is a hormone that plays an important role in the stomach’s ability to digest and absorb nutrients from the foods it eats. Gastrin can also stimulate insulin production. Decades ago, researchers tested the method of using gastrin to help treat type 1 diabetes, but were unable to devise a stable and effective treatment.

Gaba

GABA is a neurotransmitter and is a naturally produced chemical that carries information between neurons and other parts of the body. That’s Inhibition Neurotransmitters. This means slowing down or blocking their chemical connections. You can purchase GABA supplements. This is often recommended on the counter to calm people who are worried or stressed.

However, GABA does not only regulate brain and nerve activity. It also protects pancreatic cells, including islet cells, which produce insulin-secreting beta cells. In people without type 1 diabetes, beta cells usually release GABA to promote insulin production, and GABA helps to manage the amount of sugar released by the liver. GABA also affects the immune system and even suppresses some aspects of the autoimmune attack that causes type 1 diabetes, Levicure said.

In type 1 people, GABA levels are severely exhausted. However, there is no evidence that commercially available GABA supplements alone can improve the problems caused by GABA depletion in people with T1D.

Levicure’s Triple Therapy: Early Results

So far, Levicure’s triple therapy has only one retrospective chart review. It has not been tested in randomized controlled trials, the gold standard for evaluating new drug treatments.

Nevertheless, Levicure is excited by the early results. This suggests treatment.

• Stops the immune system from attacking beta cells
• Create a new beta cell
• Helps damaged beta cells regenerate
• Save an existing beta cell
• Increases insulin production
• Increases GLP-1 hormone production
• Reduces the amount of glucose produced by the liver

The results were published in 2023. A total of 19 participants were divided into two groups: newly diagnosed type 1 diabetes (within the past 12 months) and two groups: long-term type 1 diabetes.

Group 1 Results: Newly diagnosed

• 70% of participants achieved insulin independence.
• Insulin demand fell by 69%.
• A1C levels have been reduced by 38%.
• C-peptide levels increased by 147%.

C-peptides are the substances produced when the pancreas produces insulin. This is the easiest way to measure insulin production at various stages of type 1 or type 2 diabetes.

Group 2 Results: Long-standing T1D

• Insulin demand fell by 38%
• Fasting blood sugar reduced by 19%

“People with long-term type 1 diabetes also experienced improved glycemic control and reduced demand for exogenous insulin, but it was actually the early diagnosed groups who showed such unexpected results.”

Levicure’s history of triple drug therapy

To understand Levicure’s progress today, you need to know about the unforgettable and underrated leaders in Type 1 diabetes research.

Alex Rabinovitch, MD, dedicated his entire career to the challenge of regenerating beta cells in people with T1D. He is the director of diabetes research at the University of Alberta, Canada, and has received numerous awards throughout his career, including excellence in clinical research for Breakthrough T1D (formerly JDRF).

Since the 1970s, Dr. Rabinovic has identified and described the important role of the hormone gastrin in the body’s ability to produce insulin. He became a leader in the science of beta cell regeneration and discovered that the combination of PPI and DPP-4 inhibitors can restore the function of beta cells in the pancreas.

By the 2000s, his experiments had achieved significant results in mice with type 1 diabetes. The combination of DPP4 inhibitors and PPIs resulted in a surge in insulin production. However, he was unable to replicate the same results in humans.

Despite the failure, the founders of Levicure believed that Rabinovitch was in something.

“Dr. Rabinovic was ahead of his time,” says Kosherev. He and his co-founder Shmuel Levit, MD, PhD, director of the Institute for Endocrine and Diabetes at Assuta Medical Center in Tel Aviv, Israel, decided to follow the path Ravinovic began.

Koshelev says Rabinovitch was close to a major breakthrough, but lacked the key ingredient, Gaba.

Can Levicure help people with long-standing T1D?

Levicure’s trials have had promising results in a small sample of people with long-standing type 1 diabetes, significantly reducing the requirement for insulin, but the company is currently developing treatments only for newly diagnosed people.

Koshelev says Levicure cannot pursue a larger trial of treatment for people who have had T1D for many years. This is because up until now, the FDA has not been able to generate the benefits it needs for treatment.

“We need to show a significant decrease in A1C levels,” Koshelev says. Even if longtime T1D research participants significantly reduced their daily insulin needs, what is even more important for the FDA is a significant reduction in A1C levels.

“For these reasons, we need to focus our trials on treatments that protect and regenerate beta cells in people newly diagnosed with T1D,” says Koshelev.

At this point, we don’t know how long the activated beta cells will continue to produce sufficient insulin. In the long run, the business wants to partner with another lab to maximize lifespan.

“Our goal is to provide treatments that regenerate beta cells,” explains Koshelev.

Next clinical trial of Levicure

Second, Levicure is preparing for the second phase of the clinical trial. This next stage will further evaluate the effectiveness of triple medication therapy.

This gives important details about the exam. This includes a total of 50 participants and should start in the summer of 2025.

Study volunteers must:

• I was diagnosed with type 1 diabetes within the last 6 months
• At least one autoantibody test positive
• Has C-peptide levels above 100 pmol/l
• Between 16 and 45 years old
• Follow the 24-week treatment

Levicure executives expect their treatment to be slurped through the approval process.

• Green light on safety: All three components of the treatment are already considered very safe, dramatically speeding up the developmental and clinical trial process.
• Potential Acceleration Approvals: Based on phase 2 results, Levicure expects an accelerated approval process with known safety of the triple therapy combo. This also means that Levicure expects its final product to market sooner.

That may sound ambitious, but Leviqua hopes to bring the drug to the market by 2029 – just a few years away!