The End of Diabetes: The Eat to Live Plan to Prevent and Reverse Diabetes

Imagine if there was a medication you could take every day that protected you from low blood sugar (hypoglycemia). A drug that only worked when you needed it.

Zucara Therapeutics, a Toronto firm founded in 2014, is developing a drug that may protect adults living with type 1 diabetes from nighttime lows. Today, they are recruiting participants for their new clinical trial.

Diabetes, Alpha Cells, and Delta Cells

Type 1 diabetes happens when your immune system attacks and destroys your beta cells — the cells in the pancreas that produce insulin. If you’re living with type 1, you already be aware of this. What you might not know is that type 1 diabetes also interferes with the way other critical cells in the pancreas work, too. 

You see, your pancreas also has alpha, delta, gamma, and epsilon cells, all of which play a role in keeping your health and hormones properly balanced. [https://pmc.ncbi.nlm.nih.gov/articles/PMC5867580/ ]

The alpha cells and the delta cells, in particular, are supposed to chat regularly with your beta cells to prevent low blood sugars.

• Alpha cells produce the hormone glucagon. Glucagon tells your liver to unwrap stored sugar. (Yes, same as the emergency glucagon rescue medications to treat severe hypoglycemia) [ https://pmc.ncbi.nlm.nih.gov/articles/PMC8511682/ ]
• Delta cells produce the hormone somatostatin. Somatostatin talks to your alpha cells and your beta cells, telling the cells when to produce more sugar and when to back off on the insulin. [ https://pmc.ncbi.nlm.nih.gov/articles/PMC5997567/ ]

But this communication isn’t happening if you live with type 1 diabetes. This dysfunction is a cause of low blood sugar (hypoglycemia) events. 

In women and men without diabetes, the liver responds to blood sugar levels by releasing more or less sugar to keep the body safely balanced. But in people with type 1, dysfunction in the alpha and delta cells means the liver cannot respond in the same way. When your blood sugar stops dropping, the liver doesn’t release extra sugar to prevent hypoglycemia.

Zucara’s ZT-01

Zucara’s investigational therapy, ZT-01, would be the first medication of its kind to prevent low blood sugar in people who take insulin to manage diabetes. 

ZT-01 is an injectable medication that aims to tell your delta cells to reduce their production of somatostatin, which inhibits the alpha cells. By restraining somatostatin, your alpha cells can better do what they’re supposed to do: produce glucagon. ZT-01 could enhance your body’s ability to release stored sugar when your blood sugar is dropping below healthy levels.

“We know from research that people with type 1 diabetes don’t release glucagon properly,” says Zucara’s CEO, Michael Midmer. “Our drug can turn on that alpha cell role and glucagon production.”

ZT-01 still has years of development ahead of it. To date, it has completed a phase 1 clinical trial. Before drugmakers can really test the efficacy of new experimental therapies, they require to run smaller trials to test safety. 

“Building a biotech with a drug, it’s a long road, you have to go through all the steps, and it takes time,” says Midmer. “In 2016, this was just an idea.”

Although safety was its focus, the phase 1 trial also helped show that ZT-01 may be capable to prevent low or correct low blood sugar. It proved to be effective at restoring the body’s responsive production of glucagon — which triggers the release of glucose in the liver — to prevent hypoglycemia. ZT-01 increased the glucagon concentration in 90 percent of participants.

In their next experiment, a larger phase 2 study, Zucara will learn if ZT-01 can prevent blood sugar lows. Ultimately, it will help answer the question, “Does this improve life for people with type 1 diabetes?”

Zucara is focusing on overnight lows because they are so disruptive — and potentially so dangerous — for so many people with type 1 diabetes. Its injection lasts 10 to 12 hours, though they hope to eventually develop a longer-lasting formula.

“Right now,” explains Midmer, “the way the drug is delivered, we feel can cover the nighttime hours, but we’re going to monitor through the next day. It’s a peptide, which is not long-acting. We’re working with companies right now to develop a weekly dose of the drug … ideally, a once-weekly injection that slowly releases.”

Clinical Trial Participation Criteria

Zucara needs people with type 1 diabetes to volunteer for its next trial. Here’s what you need to know about participating. You might qualify for Zucara’s phase 2 clinical trial if:

• You’ve lived with type 1 diabetes for at least 5 years
• You are between the ages of 18 to 75 years old
• You experience frequent low blood sugars at night
• Your A1C is under 10 percent
• Your body mass index is between 18.5 and 33 
• You’re near one of the many participating clinics in the United States or Canada 

Zucara will provide a CGM for you to wear during the duration of the learn about — but the data will be blinded, which means you won’t be able to see it, a normal part of many clinical trials.

Diabetes Daily

The End of Diabetes: The Eat to Live Plan to Prevent and Reverse Diabetes