- HDV Insulin Lispro (HDV-LIS) met A1C non-inferiority at weeks 12 and 25, confirming comparable glycemic control to insulin lispro (LIS) with point estimate differences below the FDA required threshold of 0.1%
- HDV-LIS achieved statistically significant reductions in continuous glucose monitoring (CGM) hypoglycemia at multiple endpoints during the maintenance period
- Zero level 3 (severe) hypoglycemic events with HDV-LIS versus five with LIS
- The results indicate the potential of restoring hepatic insulin exposure during meals to improve the balance between glycemic control and the risk of hypoglycemia. Nearly 2.1 million Americans live with type 1 diabetes1 and each year approximately 20% will experience severe hypoglycemia.2,3
- Presented as an oral presentation at the 86th Scientific Sessions of the American Diabetes Association (ADA).
NEW ORLEANS, June 07, 2026 (GLOBE NEWSWIRE) — Diasome Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing portal-hepatic targeted therapies for metabolic diseases, announced Phase 2b results from OPTI-2, a potentially groundbreaking 25-week, double-blind, randomized controlled trial comparing hepatocyte-targeted vesicle insulin lispro (HDV-LIS) versus standard insulin lispro (LIS) in 226 adults with type 1 diabetes. In an oral presentation today at the 86th Scientific Sessions of the American Diabetes Association (ADA), Diasome reported that HDV-LIS maintained glycemic control with an A1C non-inferiority margin of <0,1%, behaald in week 12 en 25. CGM-gemeten hypoglykemie tijdens de binaire primaire eindpuntperiode (week 7-12) gaf de voorkeur aan HDV-LIS in 14/15 eindpunten, maar miste nipt statistische significantie. Gedurende de volgende 6 weken van het onderzoek (onderhoudsperiode) bereikte de door CGM gemeten hypoglykemie met HDV-LIS statistische significantie op meerdere eindpunten, waaronder >30% reductions in both level 2 hypoglycemic events (glucose <54 mg/dl gedurende >15 consecutive minutes) and prolonged hypoglycaemic events (glucose <70 mg/dl for more than 2 consecutive hours). Overall, CGM-measured hypoglycemia favored HDV-LIS in 47/51 endpoints in the study. Zero HDV-LIS patients experienced a level 3 (severe) hypoglycemic event, compared to five such events in the LIS group.
“Insulin therapy has always had a narrow therapeutic index: tighter glycemic control directly correlates with an increased risk of hypoglycemia. This trade-off remains a major challenge for people with type 1 diabetes,” said Klara Klein, MD, PhD, assistant professor of medicine at the University of North Carolina School of Medicine, and lead investigator on the study. “In OPTI-2, we see potential to decouple glycemic control from the risk of hypoglycemia. People randomized to HDV-LIS met similar A1C goals, but experienced fewer hypoglycemic events and no severe hypoglycemic events. If confirmed in larger studies, this could allow people with T1D to achieve glycemic goals with less concern about clinically meaningful hypoglycemia.”
Hypoglycemia risk in type 1 diabetes
Hypoglycemia remains the central dose-limiting barrier in diabetes treatment. Nearly 2.1 million Americans live with type 1 diabetes.1 Each year, approximately 20% of adults with type 1 diabetes report at least one serious hypoglycemic event, a rate that persists even among users of the most advanced automated insulin delivery systems.2,3 With standard insulin therapy, tighter glycemic control has been consistently associated with an increased risk of hypoglycemia – a link recognized since the Diabetes Control and Complications Trial (DCCT) in 1993. OPTI-2 may be the first controlled rapid-acting insulin trial to demonstrate non-inferiority of A1C while demonstrating statistically significant reductions in clinically meaningful hypoglycemia.
HDV™ Insulin Lispro
HDV (hepatocyte-directed vesicle) is a phospholipid bilayer bicelle that binds standard insulin lispro and preferentially directs it to hepatocyte receptors, restoring a more physiological pattern of hepatic insulin exposure. By restoring hepatic insulinization during meals, HDV-LIS may improve postprandial glucose disposal and hepatic glycogen storage, potentially reducing the frequency and severity of hypoglycemia.
Study design
OPTI-2 enrolled 226 adults with type 1 diabetes across 27 sites in the US and randomized them 1:1 to HDV-LIS or LIS, with unblinded continuous glucose monitoring (Dexcom G7) offered to both groups throughout the study. The trial included a 12-week dose optimization period with weekly insulin titration towards intensive glycemic targets, followed by a 13-week maintenance period with stable dosing. The prespecified primary endpoint was a binary composite assessed during dose optimization, requiring both A1C non-inferiority and superiority in at least one of the three overnight CGM-derived hypoglycemia metrics. The design had not previously been used in a blinded insulin trial. Prespecified secondary endpoints assessed the same and additional measures of hypoglycemia during the first and last six weeks of the maintenance period.
Results
Non-inferiority of A1C was confirmed at week 12 (HDV-LIS: -0.34% vs. LIS: -0.42%; estimated difference 0.08%; [95% CI: -0.06, 0.21]; p=0.26) and week 25 (HDV-LIS: -0.31% vs. LIS: -0.38%; estimated difference 0.07%; [95% CI: -0.10, 0.25]; p=0.40), which meets the FDA requirement of <0.1% A1C point estimate difference at both time points.
At week 12, 14/15 prespecified CGM hypoglycemia point estimates favored HDV-LIS and met non-inferiority; however, statistically significant superiority was narrowly missed during the 12-week period of active titration. During the maintenance period, the FDA’s preferred time point for assessing hypoglycemia data, the HDV-LIS signal for hypoglycemia risk reduction was significantly enhanced. HDV-LIS produced statistically significant reductions in multiple pre-specified secondary endpoints during this period:
- 24-hour level 2 events: 28% reduction (ratio 0.72; p=0.014)
- Level 2 daytime hypoglycaemic events: 33% reduction (ratio 0.67; p=0.009)
- 24-hour percent time below 54 mg/dL: 28% reduction (rate ratio 0.72; p=0.017)
- Percentage of daytime time below 54 mg/dl: 32% reduction (rate ratio 0.68; p=0.010)
- 24-hour prolonged hypoglycemia events: 36% reduction (ratio 0.64; p=0.029)
Across the study, the exposure-adjusted incidence of level 2 hypoglycemia was 25% lower with HDV-LIS than LIS, and zero HDV-LIS-treated participants experienced a level 3 severe hypoglycemic event, compared to five in the LIS group (p=0.0598).
Treatment-emergent adverse events were similar between groups (53.6% HDV-LIS vs. 50.0% LIS). Serious treatment-emergent adverse events occurred in one HDV-LIS participant (0.9%) and eight LIS participants (7.0%). No deaths, diabetic ketoacidosis events, or clinically meaningful hepatic safety signals were observed in either group.
“OPTI-2 has demonstrated that HDV-LIS may overcome the trade-off between tight glycemic control and the risk of hypoglycemia, with no serious hypoglycemic events during six months of meal dosing and a 25% reduction in level 2 hypoglycemia over the entire study. These results, combined with A1C non-inferiority – the FDA’s preferred endpoint – now demonstrated in two consecutive blinded studies, give us clear support to to advance the program to Phase 3.,” said Robert Geho, Chief Executive Officer of Diasome. “We also believe the HDV platform has broader potential, exploring the same liver-targeted approach in metabolic diseases and obesity, where targeted liver delivery can meaningfully improve clinical outcomes.”
About OPTI-2
OPTI-2 (NCT06238778) was a phase 2b, double-blind, randomized, parallel-group trial conducted at 27 sites in the United States. The study enrolled 226 adults with type 1 diabetes receiving multiple daily injection (MDI) treatment, and randomly randomized participants 1:1 to bolus insulin with HDV-LIS or standard LIS, both with once-daily insulin degludec as basal insulin and continuous glucose monitoring (Dexcom G7) for the 25-week treatment period. The study included a 12-week dose optimization period with weekly CGM-guided titration, followed by a 13-week dose maintenance period.
About Diasome medicines
Diasome is a clinical-stage biopharmaceutical company developing therapies that act at the portal hepatic region, the center of metabolic regulation. The company’s proprietary HDV™ platform delivers therapies preferentially to the liver and portal vein. Diasome applies HDV in insulin, GLP-1 and serotonin programs. Diasome’s lead program, HDV-Insulin, is designed to decouple improved glycemic control from the increased risk of hypoglycemia typically associated with this essential drug for millions of patients worldwide. For more information about Diasome, visit Diasome.com or follow us further LinkedIn or X.
Contacts
Media & Investors:
Adam Silverstein
[email protected]
1 Centers for Disease Control and Prevention. National Diabetes Statistics Report website. https://www.cdc.gov/diabetes/php/data-research/index.html.
2 Sherr JL, et al. Severe hypoglycemia and impaired awareness of hypoglycemia persist in people with type 1 diabetes despite use of diabetes technology: results from a cross-sectional study. Diabetes care. 2024;47(6):941–947. doi:10.2337/dc23-1765.
3 Sherr JL, et al. Persistence of severe hypoglycemia and reduced awareness of hypoglycemia in people with type 1 diabetes despite technology use: a follow-up study. Diabetes care. Feb 26, 2026: dc25-2345. doi:10.2337/dc25-2345.
A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/4b351397-b1fd-46e2-bed6-a282482409d4
