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How Glucagon Could Be the Next Frontier in Managing Type 1 Diabetes

-Sony Salzman

For most people with diabetes, glucagon forms an important part of our emergency kits. As a medication, it treats critically low blood sugars. However, it’s also a key hormone naturally created by the pancreas — just like insulin.

A new treatment that alters glucagon action could dramatically reduce the amount of insulin used by people with type 1 diabetes.

Twelve years ago, Dr. Hai Yan’s team discovered this potentially revolutionary drug while working at the pharmaceutical firm Amgen. AMG 477, as the drug was called, works by blocking glucagon activity as the body releases the hormone into the bloodstream to raise blood sugar levels.

In people without diabetes, glucagon and insulin work together to maintain normal blood sugars. For those of us with diabetes, naturally-occurring glucagon raises blood sugar without being effectively counteracted. That means that patients need to take insulin not only for food, but to balance the glucagon their bodies make. In stressful situations, your body will actually release a cocktail of hormones including adrenaline, cortisol, and glucagon, spiking blood sugar without eating or drinking a single carb.

Yan discovered that by interfering with the glucagon pathway, when overactive, AMG 477 could be used alongside standard insulin therapy. For people with type 1 diabetes, this two-pronged approach could help patients achieve better management while using less insulin.

Discovering and refining the drug

Amgen promoted Yan after his discovery of AMG 477, but eventually the company decided not to prioritize AMG 477’s development. At that point, Yan took a leap of faith, recruiting a few like-minded scientists to pool their savings and purchase AMG 477 outright.

Yan and his colleague Tom Boone founded REMD Biotherapeutics in 2011. These scientists-turned-entrepreneurs re-christened their drug REMD 477, and immediately began generating promising preclinical data.

“We knew we were onto something,” Yan told us. “Glucagon and insulin are partners. The theory [of diabetes treatment] has been insulin-centric for 100 years and people have totally forgot the other part of the story.”

Today, it looks like Yan’s gamble is paying off. Though he believes REMD 477 could help patients with type 1 or type 2 diabetes, Yan’s team prioritized research into type 1; patients with type 1 diabetes still rely on taking insulin for their entire lives.

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The T1D Exchange Diabetes Innovation Challenge selected REMD Biotherapeutics as a semi-finalist in 2016, and the firm has gone on to achieve major corporate milestones in the intervening years.

Successfully reducing insulin usage

The Phase I study evaluated REMD 477 against a placebo injection in 21 patients with type 1 diabetes. Those who received the single experimental injection were able to reduce their daily insulin use by 26 percent, or about 12 units, compared to the placebo group. Even better the injection also appeared to improve glycemic management by reducing hyperglycemia without increasing hypoglycemia.

Yan said he’s constantly fighting the so-called ‘dogma’ among the scientific and medical community – one that prioritizes insulin as the be-all, end-all diabetes treatment.

“People always think ‘insulin’ for everything,” Yan explained. “In the type 1 diabetes field, people are afraid to go down the glucagon pathway.”

According to Yan, REMD Biotherapeutics’ Phase 1 results represent “the first time ever that people tried to use this approach [of] blocking glucagon pathways to normalize glucose levels and reduce insulin use.”

REMD is now enrolling patients for a Phase II trial of REMD 477, which will evaluate multiple doses of REMD 477. The trial will enroll 150 patients with type 1 diabetes, and the company estimates the trial could be wrapped up by June 2019.

“We believe in this project — that’s why we came out of our own savings,” said Yan. “Not everything in the textbook is correct.”

 

 

 

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