HDV-Insulin Lispro (hepatocyte-directed vesicle)
Diasome Pharmaceuticals
What it is
An investigational mealtime insulin lispro from Diasome wrapped in a liver-targeting phospholipid carrier (HDV) that steers a fraction of each dose to the liver, aiming to restore more natural hepatic insulin exposure. A Phase 2b type 1 diabetes trial matched standard lispro on A1C with less hypoglycemia.
Editorial review: .
Most recent recorded citation dates: 2026-06-07; 2026-06-07. Some dates overlap at their stated precision or share the same date. Only explicit date metadata is included; an undated citation may be newer. This does not mean every claim was reviewed on that date.
Trial status, labels and access can change between reviews. How we review the evidence · How to read the evidence
Evidence behind this assessment
Key evidence notes. Study results, product eligibility and access answer different questions.
- Who was studied?
- Study populations and analysis groups vary. Product age limits alone do not describe who was studied.See the linked studies and their populations →
- Benefit or performance
- Consistency: Phase 2b OPTI-2 (226 adults, 25 weeks) met A1C non-inferiority at weeks 12 and 25 — the second consecutive blinded trial to do so — supporting reproducible glycemic control. The prespecified composite primary endpoint was not met: hypoglycemia superiority was not established in the primary titration window; positive maintenance results were secondary.[2]
- Important harms and treatment burden
- Read the safety discussion and original sources. A missing summary does not establish safety.
- Approval and country access
- Country-specific approval and access are not summarized in this record.Approval, trial recruitment, local supply and funding are separate. Check the cited label or access source.
- Follow-up and remaining uncertainty
- Read the full discussion and original sources for follow-up duration and study limitations.
Research status alone does not establish approval, clinical benefit or local availability. This record cites company or conference reports. Those sources may describe interim findings; their source type is shown in the source list.
Editorial score: calculation and evidence
A weighted editorial judgment on a 0–100 scale, not a probability of success or a measured treatment effect. Higher criterion scores mean more favorable assessments.
Default calculation: 55 × 20 + 55 × 25 + 60 × 15 + 65 × 20 + 70 × 10 + 12 × 10 = 5495; divide by total weight 100. Unrounded weighted result: 54.95.
Mealtime convention: HDV carries ordinary lispro, so subcutaneous onset is broadly lispro-like; the innovation is hepatic targeting, not faster absorption. Scored near a standard rapid analog.[2]
Mealtime convention: peak action is reported to track standard lispro pharmacokinetics; the goal is redistributing where insulin acts (liver) rather than shifting time-to-peak.[2]
The sponsor reports fewer extended hypoglycemia events in secondary maintenance-period analyses; the primary composite endpoint was not met. These findings do not establish a shorter pharmacokinetic tail. The tail score remains an editorial estimate, not a measured duration.[4]
Phase 2b OPTI-2 (226 adults, 25 weeks) met A1C non-inferiority at weeks 12 and 25 — the second consecutive blinded trial to do so — supporting reproducible glycemic control. The prespecified composite primary endpoint was not met: hypoglycemia superiority was not established in the primary titration window; positive maintenance results were secondary.[2]
Exercise-flex convention (less hypoglycemia is better): zero Level 3 (severe) hypoglycemia events over six months and a ~25% reduction in Level 2 hypoglycemia vs standard lispro suggest a wider safety margin, relevant to active days.[2]
Access convention (cheaper/more available is better): not approved anywhere, no price; Phase 3 still pending as of 2026, so currently inaccessible.[1]
Insulins are scored relative to their role peers (see tags: rapid, ultra-rapid, basal, inhaled). A basal insulin's onset score compares it to other basals, not to mealtime insulins.
The full picture
HDV-Insulin Lispro takes a different angle on the mealtime insulin problem. Rather than chasing speed, it tries to fix where insulin goes. In a person without diabetes, the pancreas releases insulin into the portal vein, so the liver sees a high concentration first. Injected insulin bypasses that route, leaving the liver relatively under-exposed and the periphery over-exposed — a pattern linked to hypoglycemia. Diasome's hepatocyte-directed vesicle (HDV) is a tiny phospholipid carrier that binds ordinary insulin lispro and steers a fraction of each dose preferentially to liver cells, aiming to restore a more physiologic hepatic insulin signal.
The headline evidence is the Phase 2b OPTI-2 trial: 226 adults with type 1 diabetes, randomized double-blind to mealtime HDV-lispro or standard lispro, both on once-daily degludec, over 25 weeks with continuous glucose monitoring. HDV-lispro met the FDA's A1C non-inferiority threshold at both 12 and 25 weeks. The composite primary endpoint was not met, because hypoglycemia superiority was not established in the primary titration window. Positive maintenance-period hypoglycemia findings were secondary. Severe events were numerically fewer: no severe (Level 3) hypoglycemia events across six months, versus five in the standard-lispro group, and roughly a25% reduction in Level2 hypoglycemia across the study. The severe-event comparison had p=0.0598, so it did not establish statistical superiority.4
Because it carries conventional lispro, no faster onset or earlier peak is claimed; the reported value proposition is a wider safety margin, not raw speed. It is not approved, and Diasome states it intends to proceed to Phase 3.
Coming soon
ETA · Phase 2b (OPTI-2) reported June 2026; company states it intends to advance to Phase 3. No regulatory approval as of 2026.
- →Diasome plans to advance HDV-Insulin Lispro to Phase 3 after two consecutive blinded trials met A1C non-inferiority · 2026 onward
- →If approved, would be positioned as a mealtime insulin focused on cutting hypoglycemia rather than raw speed
Sources
- [1]
- [2]
- [3]
- [4]Diasome OPTI-2 phase 2b results and prespecified primary endpoint · Manufacturer · 2026-06-07
Diasome sponsor report, 7 June 2026.