HDV-Insulin Lispro (hepatocyte-directed vesicle)
Diasome Pharmaceuticals
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.
The scorecard
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 tracks standard lispro pharmacokinetics; the goal is redistributing where insulin acts (liver) rather than shifting time-to-peak.[2]
Mealtime convention (shorter tail is better): similar to lispro, but the liver-targeting mechanism is associated with fewer late lows, which functionally softens the tail's hypoglycemia risk.[2]
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.[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. On safety it looked better: no severe (Level 3) hypoglycemia events across six months, versus five in the standard-lispro group, and roughly a 25% reduction in Level 2 hypoglycemia.
Because it carries conventional lispro, its onset and peak are lispro-like; the value proposition is a wider safety margin, not raw speed. It is not approved, and Diasome says 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 a mealtime insulin focused on cutting hypoglycemia rather than raw speed
Sources
- [1]Phase 2b Trial Comparing HDV-Insulin Lispro to Insulin Lispro in Adults With Type 1 Diabetes Receiving Insulin Degludec (OPTI-2), NCT06238778 · registry
- [2]Diasome Presents Phase 2b Data Demonstrating HDV-Insulin Lispro Maintains Glycemic Control While Reducing Hypoglycemia in Adults with Type 1 Diabetes · news · 2026-06-07
- [3]Geho WB, et al. Hepatic-Directed Vesicle Insulin: A Review of Formulation Development and Preclinical Evaluation. J Diabetes Sci Technol · peer-reviewed