A new concept for targeting insulin toward the liver could lead to people with diabetes needing less of it to control glycated hemoglobin (A1C) and avoid hypoglycemia.
Amid the debate about why insulin costs so much lies a second question: if the hormone can be delivered more efficiently, will people with diabetes need less insulin?
It’s not just a question that’s come up in the era of the artificial pancreas, as people with type 1 diabetes (T1D) work with technology that uses an algorithm to anticipate their blood glucose levels and make constant adjustments to their insulin needs.1
A company called Diasome is pushing the idea further, by trying to take insulin to the place where it would go if created by islet cells and released by a human pancreas: straight to the liver.2
According to Robert Geho, MBA, Diasome’s co-founder and chief executive officer, the idea is to gain control over the element of insulin delivery that has thus far eluded patients and doctors—where insulin goes when it’s administered.
In an interview earlier this year with Evidence-Based Diabetes Management™(EBDM), Geho explained that patients can control how much insulin they take, and there have been many advances in how fast it acts. But until now, delivery is still under the skin, not targeted to the organ where insulin is normally stored in people without diabetes.
Years in development, Diasome has created a nanotechnology additive, consisting of thousands of phospholipid discs, which are added to insulin and bind to it, causing the insulin to be directed toward the liver with no safety issues. Through this method, called hepatocyte-directed vesicle (HDV) technology, the liver can now store and distribute insulin throughout the body. The process yields 2 important results: patients should need less insulin, and there is less risk of hypoglycemia. Recent results confirm this is especially true in patients with poor glycemic control.
Data presented in June at the American Diabetes Association (ADA) Scientific Sessions in San Francisco and published this week in Diabetes Care, an official ADA journal,3 are important steps toward bringing the company’s additive through the development process. These are data from ISLE-1, the phase 2b study that randomized 176 patients 2:1 to either use insulin lispro (Humalog) with the HDV additive (HDV-L) or insulin lispro (LIS) alone. The primary outcome of the study was to show glycated hemoglobin (A1C) noninferiority of HDV-L, with a prespecified margin of ≤0.4%. Results showed the following:
Asked by EBDM™ why the additive appeared to produce a greater effect among patients with poorly controlled glucose, Geho replied via email that the results show that HDV had “physiological effect across the A1C spectrum.” Those with less glycemic control at the outset achieved reductions in A1C and a reduction in time with blood glucose below 54 mg/dL, “all with less insulin dosing,” he said.
“This is the combination of effects that a more physiological form of insulin should provide,” Geho said.
The higher levels of hypoglycemia in group with lower A1C levels at baseline could be due to patients using more basal insulin than needed, and thus Diasome is conducting OPTI-1, an open-label phase 2 study for patients with A1C between 6.5% and 8.5%. This trial is designed to provide additional dosing guidance based on the phase 2 data from ISLE-1, according to a statement from the company.4
Although ISLE-1 used HDV with insulin lispro, Geho said, “Diasome has designed HDV to be insulin agnostic, and we believe that HDV is most appropriately viewed by regulators as an adjunctive therapy to insulin.” It is also compatible with pumps, pens, vials, and syringes, he said.
Phase 3 testing will begin in 2020, he said.