Diasome Prepares Phase III Tests of Liver-Targeted Insulin for Type 1 Diabetes

For people with type 1 diabetes (T1D), insulin remains essential, but managing glucose without dangerous lows is still a daily challenge. Diasome’s Phase IIb results suggest that directing insulin toward the liver could help address that tradeoff. The New Orleans company is now finalizing plans for pivotal studies of its liver-targeted insulin formulation.

The candidate, HDV-L, combines standard insulin lispro with Diasome’s hepatocyte-directed vesicle (HDV) platform. The premise is to change where insulin travels after administration: instead of leaving much of the dose to interact with receptors in peripheral tissues such as muscle and fat, the formulation is designed to direct more of it toward the liver.

Changing insulin’s route

The liver helps regulate blood glucose and fat metabolism, and it normally receives insulin through the portal vein. Diasome says its formulation aims to more closely reproduce that delivery pattern by guiding insulin and other biologic molecules to hepatocytes, the liver’s principal cells.

HDV is a phospholipid bicelle, a disc-like structure with a bilayer designed to bind insulin lispro. Its negatively charged surface can bind positively charged proteins and peptides. Biotin-PE, incorporated into the membrane, is intended to support uptake by hepatocytes, where the sodium-dependent multivitamin transporter is highly expressed. Diasome says each disc can bind as many as 100 proteins or peptides.

The platform is intended for peptides, proteins and hormones delivered by injection under the skin or orally. The company’s argument is that targeting the liver could help biologics reach a key metabolic organ despite competing receptors elsewhere in the body.

“Either subcutaneously or via oral administration, we’re able to preferentially deliver enough of those payloads into the liver and the portal vein that feeds the liver to basically mimic the endogenous release of those materials,” Robert Geho, Diasome’s co-founder and CEO, told GEN.

He described the approach as adding chemistry to established active pharmaceutical ingredients without tying the platform to a single drug. “Diasome is taking these commonly used APIs [active pharmaceutical ingredients] and adding very elegant chemistry to them in kind of an API-agnostic fashion and changing the biodistribution in an important way to enable the liver, especially, to just basically turn back on in response to those targeted molecules.”

Phase IIb results set up pivotal planning

The company’s next step is to settle the design of its Phase III program. That work includes drafting the protocol, calculating statistical power, determining how many studies to run and selecting the insulin for the trials. Geho said Diasome expects to discuss its pivotal plan with the FDA.

The evidence so far comes from OPTI-2, a 25-week, double-blind Phase IIb study of 226 adults with T1D who used multiple daily insulin injections. Participants were randomized 1:1 to insulin lispro or HDV-L, with continuous glucose monitoring. The study included 12 weeks of dose optimization followed by 13 weeks of maintenance treatment.

Results first published in June and presented at the European Association for the Study of Diabetes’ 62nd Annual Meeting in Milan, held September 28 to October 2, 2026, found HDV-L was non-inferior to lispro for reducing A1C. The formulation also showed reductions in clinically meaningful hypoglycemia, including severe events, while maintaining glycemic control.

Five participants in the lispro group experienced severe hypoglycemia, compared with none in the HDV-L group; the reported p-value was 0.0598. Treatment-emergent adverse events were similar between groups. Serious events were reported in one HDV-L participant and eight participants receiving lispro. The trial reported no deaths or cases of diabetic ketoacidosis.

Researchers presented additional OPTI-2 analyses at the inaugural Breakthrough T1D Clinical & Research Congress in Philadelphia, October 9–11. Compared with lispro, HDV-L had lower exposure-adjusted incidence rates per person-year for level 1 or 2 hypoglycemia, level 2 hypoglycemia and level 1 hypoglycemia.

Geho sees reducing hypoglycemia as a possible route to tighter glucose control. “Hypoglycemia risk is the single biggest rate-limiting challenge to achieving glycemic control in people with insulin-deficient diabetes,” he said. “If you can fix that, you can actually enable people to take more insulin safely, which will have a big impact on their A1C control.” He added that the need remains even as insulin pumps and glucose monitors improve.

Other approaches are advancing, with mixed results

Diasome is entering a competitive area where drug developers are testing ways to supplement insulin or address the metabolic challenges that accompany T1D. GLP-1 and GIP receptor agonists have become major treatments for type 2 diabetes, but none is indicated for T1D. Earlier this year, six professional groups issued a consensus statement on their safe use in T1D management.

Eli Lilly is expected to report results in November from two Phase III trials of tirzepatide, its GIP/GLP-1 agonist marketed as Mounjaro. SURPASS-T1D-1 is a 49-week, 905-participant study, while SURPASS-T1D-2 runs for 20 months and enrolled 465 people. Both compare tirzepatide with placebo in adults with T1D who have obesity or are overweight. Lilly reported $18.605 billion in Mounjaro revenue in the first half of 2026, more than double the $9.041 billion recorded in the same period a year earlier. The company’s third-quarter results are scheduled for October 29.

Lexicon Pharmaceuticals, meanwhile, is waiting for data from STENO1, a Phase III trial of sotagliflozin sponsored by Steno Diabetes Center Copenhagen. Lexicon has said it hopes to resubmit an application for the drug in T1D by year-end, depending on the results. The FDA rejected its 2024 application for sotagliflozin, then proposed as an add-on to insulin for adults with T1D and chronic kidney disease. Lexicon subsequently launched STENO1 and two investigator-initiated studies: SUGARNSALT at Joslin Diabetes Center (NCT06217302) and SOPHIST at the University of Dundee (NCT06435156).

Sotagliflozin inhibits sodium-glucose co-transporters 1 and 2 and is marketed as Inpefa for heart failure. Another drug in the class, dapagliflozin, was rejected by the FDA in 2019 as an insulin add-on for adults with T1D. Researchers have since studied it in combinations with pioglitazone, sold by Takeda as Actos (NCT03878459), and with insulin and semaglutide, marketed by Novo Nordisk as Wegovy for obesity and Ozempic for type 2 diabetes (NCT03899402). AstraZeneca sells dapagliflozin as Farxiga for type 2 diabetes and certain heart and kidney conditions.

There have also been setbacks. Sanofi’s Tzield (teplizumab), first approved in 2022 for children aged eight and older as a disease-modifying treatment for autoimmune T1D, received a broader label in June covering children aged one and older with Stage 2 disease. Roche, by contrast, ended development of acmopatide (CT-868), a once-daily GLP-1/GIP agonist for T1D with obesity, despite positive Phase II findings reported a month earlier. Roche said it would focus its T1D work on once-weekly injectable enicepatide (CT-388), which CEO Thomas Schinecker described as having potential across multiple indications. The company acquired both candidates through its 2024 purchase of Carmot Therapeutics for up to $3.1 billion.

Company plans extend beyond the trial

Geho has also pointed to tolerability as a reason for pursuing more physiologic delivery. He cited reports of high discontinuation among GLP-1 users, while acknowledging cost and side effects as major issues. A 2025 University of Pennsylvania and Truveta study found that 46.5% of people with type 2 diabetes and 64.8% of those without it stopped GLP-1 treatment within a year; some later restarted during that period. The higher, 85% two-year discontinuation figure cited by Geho came from a 2024 analysis by pharmacy benefit manager Prime Therapeutics based on claims data for commercially insured members.

Diasome was founded in 2005 by Geho and his father, W. Blair Geho, MD, PhD. The elder Geho studied pharmacology under Earl W. Sutherland Jr., whose work on hormone signaling and cyclic adenosine monophosphate contributed to his 1971 Nobel Prize in Physiology or Medicine.

Diasome says it has raised about $85 million, with past investors including Eli Lilly and the JDRF T1D Fund, now called T1D Fund, A Breakthrough T1D Venture. Its most recently announced financing was the first close of a Series C round in December 2023; the amount was not disclosed, though it has been reported as $9.5 million. Geho said the company is working toward a Series D financing.

The workforce currently numbers roughly 20 to 25, including full-time employees and significant consultants. Geho expects full-time headcount to grow by about 25% to 30% over the next several months. For now, the key milestone is the pivotal plan: OPTI-2 gives Diasome a clinical rationale to test whether liver-directed insulin can reduce hypoglycemia while preserving glucose control at a larger scale.