- 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 FDA-required 0.1% threshold
- HDV-LIS achieved statistically significant reductions in continuous glucose monitoring (CGM)-measured hypoglycemia across multiple endpoints during the maintenance period
- Zero Level 3 (severe) hypoglycemic events with HDV-LIS vs. five with LIS
- Results point to the potential of restoring mealtime liver insulin exposure to improve the balance between glycemic control and hypoglycemia risk. Nearly 2.1 million Americans live with type 1 diabetes1 and each year, approximately 20% will experience a severe hypoglycemia event.2,3
- Presented as an oral presentation at the American Diabetes Association (ADA) 86th Scientific Sessions
NEW ORLEANS, June 07, 2026 (GLOBE NEWSWIRE) — Diasome Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing portal-hepatic targeted therapies for metabolic disease, announced Phase 2b results from OPTI-2, a potentially groundbreaking 25-week, double-blind, randomized controlled trial comparing hepatocyte-directed vesicle insulin lispro (HDV-LIS) with standard insulin lispro (LIS) in 226 adults with type 1 diabetes. In an oral presentation today at the American Diabetes Association (ADA) 86th Scientific Sessions, Diasome reported that HDV-LIS maintained glycemic control with an A1C non-inferiority margin of <0.1% met at Weeks 12 and 25. CGM-measured hypoglycemia during the binary primary endpoint period (weeks 7-12) favored HDV-LIS in 14/15 endpoints but narrowly missed statistical significance. During the next 6 weeks of the study (maintenance period), CGM-measured hypoglycemia with HDV-LIS reached statistical significance in multiple endpoints, including >30% reductions in both Level 2 hypoglycemic events (glucose <54 mg/dL for >15 consecutive minutes) and extended hypoglycemic events (glucose <70 mg/dL for greater than 2 consecutive hours). Overall, CGM-measured hypoglycemia favored HDV-LIS in 47/51 endpoints in the trial. Zero HDV-LIS patients experienced a Level 3 (severe) hypoglycemic event, compared with five such events in the LIS group.
“Insulin therapy has always had a narrow therapeutic index: tighter glycemic control directly correlates with increased risk of hypoglycemia. This tradeoff continues to be a major challenge for people living with type 1 diabetes,” said Klara Klein, MD, PhD, Assistant Professor of Medicine, University of North Carolina School of Medicine, and principal investigator in the trial. “In OPTI-2, we see potential to decouple glycemic control from hypoglycemia risk. People randomized to HDV-LIS met similar A1C targets but experienced fewer hypoglycemic events and no severe hypoglycemic events. If confirmed in larger studies, this could allow people living with T1D to achieve glycemic targets with less concern about clinically meaningful hypoglycemia.”
Hypoglycemia Risk in Type 1 Diabetes
Hypoglycemia remains the central dose-limiting barrier in diabetes management. Nearly 2.1 million Americans live with type 1 diabetes.1 Each year, about 20% of adults with type 1 diabetes report at least one severe 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 increased hypoglycemia risk—a coupling recognized since the Diabetes Control and Complications Trial (DCCT) in 1993. OPTI-2 may be the first controlled rapid-acting insulin trial to show A1C non-inferiority while simultaneously 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 physiologic pattern of hepatic insulin exposure. By restoring mealtime liver insulinization, 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 U.S. sites and randomized them 1:1 to HDV-LIS or LIS, with unblinded continuous glucose monitoring (Dexcom G7) provided to both groups throughout the study. The trial comprised a 12-week dose optimization period with weekly insulin titration toward 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 three nocturnal CGM-derived hypoglycemia metrics. The design had not been previously used in a blinded insulin trial. Prespecified secondary endpoints assessed the same and additional hypoglycemia metrics during the first and last six weeks of the maintenance period.
Results
A1C non-inferiority 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), meeting the FDA’s required <0.1% A1C point-estimate difference at both timepoints.
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 window of active titration. During the maintenance period, the FDA’s preferred time for assessing hypoglycemia data, the HDV-LIS hypoglycemia risk reduction signal strengthened considerably. HDV-LIS produced statistically significant reductions across multiple prespecified secondary endpoints throughout this period:
- 24-hour Level 2 events: 28% reduction (rate ratio 0.72; p=0.014)
- Daytime Level 2 hypoglycemic events: 33% reduction (rate ratio 0.67; p=0.009)
- 24-hour percent time below 54 mg/dL: 28% reduction (rate ratio 0.72; p=0.017)
- Daytime percent time below 54 mg/dL: 32% reduction (rate ratio 0.68; p=0.010)
- 24-hour extended hypoglycemia events: 36% reduction (rate ratio 0.64; p=0.029)
Across the full study, the exposure-adjusted incidence rate of Level 2 hypoglycemia was 25% lower with HDV-LIS than with LIS, and zero HDV-LIS-treated participants experienced a Level 3 severe hypoglycemic event, compared with five in the LIS group (p=0.0598).
Treatment-emergent adverse events were comparable 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 demonstrated that HDV-LIS can potentially break the tradeoff between tight glycemic control and hypoglycemia risk, with no severe hypoglycemic events in six months of mealtime dosing and a 25% reduction in Level 2 hypoglycemia across the full study. These results, combined with A1C non-inferiority – the FDA’s preferred endpoint – now demonstrated in two consecutive blinded trials, give us clear support to advance the program into Phase 3,” said Robert Geho, Chief Executive Officer of Diasome. “We also believe the HDV platform has broader potential, with the same liver-targeting approach being explored in metabolic disease and obesity, where targeted hepatic delivery may meaningfully improve clinical outcomes.”
About OPTI-2
OPTI-2 (NCT06238778) was a Phase 2b, double-blind, randomized, parallel-group study conducted at 27 sites in the United States. The trial enrolled 226 adults with type 1 diabetes on multiple daily injection (MDI) therapy and 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) worn throughout 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 Pharmaceuticals
Diasome is a clinical-stage biopharmaceutical company developing therapies to act in the portal-hepatic region, the center of metabolic regulation. The company’s proprietary HDV™ platform delivers therapeutics preferentially to the liver and portal vein. Diasome is applying HDV across insulin, GLP-1, and serotonin programs. Diasome’s lead program, HDV-Insulin, is designed to decouple improved glycemic control from the increased hypoglycemia risk that typically accompanies this essential medicine for millions of patients globally. For more information about Diasome, visit Diasome.com or follow us on LinkedIn or X.
Contacts
Media & Investors:
Adam Silverstein
adam@scientpr.com
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 survey. Diabetes Care. 2024;47(6):941–947. doi:10.2337/dc23-1765.
3 Sherr JL, et al. Persistent burden of severe hypoglycemia and impaired awareness of hypoglycemia among people with type 1 diabetes despite technology use: a follow-up survey. Diabetes Care. 2026 Feb 26: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
