Ultra-rapid lispro (Lyumjev)

Ultra-rapid lispro (URLi), sold as Lyumjev, is a rapid-acting mealtime insulin — taken at the start of a meal to cover the carbohydrates in it.¹ It is the same insulin molecule as Humalog (insulin lispro) but reformulated with two extra ingredients: treprostinil, which widens the small blood vessels under the skin, and citrate, which loosens the vessel walls so insulin can cross into the blood faster.²³ The goal is to chase the one thing standard analogs do poorly — get insulin working quickly enough to blunt the spike from a meal.

How fast is it? After a subcutaneous injection, insulin appears in the blood about 1 minute later, reaches half its early concentration at roughly 13 minutes (versus ~25 minutes for Humalog), and peaks (tmax) around 57 minutes.¹ In a euglycemic clamp study, insulin action started 11-12 minutes sooner than Humalog and was three-fold greater over the first 30 minutes.⁴ The glucose-lowering peak still lands around 2-3 hours, with a total duration of roughly 4.6-7.3 hours depending on dose.¹ So it is fast at the front end, but it is still subcutaneous insulin — far slower than a healthy pancreas, which releases insulin into the blood the moment glucose rises.

The tail matters too. Because more of the dose is delivered early, less lingers late: exposure after 3 hours is cut by roughly 39-41%, and total duration is 34-88 minutes shorter than Humalog.⁴⁵ Insulin action beyond 4 hours is 44-54% lower as well.⁴ A shorter tail means less "insulin stacking" and fewer late post-meal lows.

Absorption variability and head-to-head speed. In a direct comparison against Fiasp (faster aspart), Humalog and NovoRapid, URLi reached early half-maximal concentration 6 minutes faster than Fiasp and 13-14 minutes faster than the standard analogs — and its early glucose curve most closely matched healthy controls.⁶ Like all injected insulin, absorption varies with site, dose and blood flow, so real-world timing is less tidy than clamp numbers.

Behaviour around exercise and meal timing. A faster off-rate and shorter tail mean slightly less active insulin hanging around during activity, though no exercise-specific benefit has been formally proven. Usefully, the label allows dosing at the start of a meal or up to 20 minutes after it begins — handy for unpredictable appetites or kids.¹

Delivery and approvals. Lyumjev is given by injection (U-100 and U-200 pens/vials), by insulin pump (U-100), and intravenously under medical supervision.¹ The FDA approved it on 15 June 2020 for adults with type 1 and type 2 diabetes;⁷ the EU authorised it on 24 March 2020, now covering ages 1 and up.² In the 26-week phase 3 PRONTO-T1D trial (1,222 adults), mealtime URLi was non-inferior to lispro on HbA1c and superior on 1- and 2-hour post-meal glucose, with 37% fewer lows beyond 4 hours after meals — but injection-site reactions were more common (2.9% vs 0.2%).⁸

Access and cost. Lyumjev is a branded follow-on insulin with no biosimilar competitor; in the US its list price is relatively high, though Lilly's monthly out-of-pocket cap and savings cards lower the cost paid by many.⁹

What's coming. URLi is increasingly studied inside automated insulin delivery (AID) systems, where its speed could tighten closed-loop control — in-silico work suggests pump settings must be re-tuned (faster insulin needs adjusted ratios) to capture the benefit.¹⁰ But the core ceiling remains: even the fastest subcutaneous insulin can't fully solve unannounced meals, which is why we still track this against the insulin-speed gap.

References

1. Eli Lilly. Lyumjev (insulin lispro-aabc) prescribing information. FDA (2020). https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761109s000lbl.pdf ↩ ↩² ↩³ ↩⁴ ↩⁵

2. European Medicines Agency. Lyumjev (insulin lispro) — EPAR medicine overview. EMA (2020, name change 2021). https://www.ema.europa.eu/en/medicines/human/EPAR/lyumjev ↩ ↩²

3. Heise T, Piras de Oliveira C, Juneja R, et al. What is the value of faster acting prandial insulin? Focus on ultra rapid lispro. Diabetes Obes Metab (2022). https://doi.org/10.1111/dom.14773 ↩

4. Linnebjerg H, Zhang Q, LaBell E, et al. Pharmacokinetics and glucodynamics of ultra rapid lispro versus Humalog in younger and elderly patients with type 1 diabetes. Clin Pharmacokinet (2020). https://doi.org/10.1007/s40262-020-00903-0 ↩ ↩² ↩³

5. Shiramoto M, Nasu R, Oura T, et al. Ultra-rapid lispro results in accelerated insulin lispro absorption and faster early insulin action vs Humalog in Japanese patients with type 1 diabetes. J Diabetes Investig (2020). https://doi.org/10.1111/jdi.13195 ↩

6. Heise T, Linnebjerg H, Coutant D, et al. Ultra rapid lispro lowers postprandial glucose and more closely matches normal physiological glucose response compared to other rapid insulin analogues. Diabetes Obes Metab (2020). https://doi.org/10.1111/dom.14094 ↩

7. Eli Lilly. FDA approves Lyumjev (insulin lispro-aabc injection), Lilly's new rapid-acting insulin. PR Newswire (15 Jun 2020). https://www.prnewswire.com/news-releases/fda-approves-lyumjev-insulin-lispro-aabc-injection-lillys-new-rapid-acting-insulin-301077294.html ↩

8. Klaff L, Cao D, Dellva MA, et al. Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: PRONTO-T1D. Diabetes Obes Metab (2020). https://doi.org/10.1111/dom.14100 ↩

9. GoodRx. Lyumjev prices, coupons & savings tips. GoodRx (2026). https://www.goodrx.com/lyumjev ↩

10. Colmegna P, Diaz CJL, Garcia-Tirado J, et al. Adjusting therapy profiles when switching to ultra-rapid lispro in an advanced hybrid closed-loop system: an in silico study. J Diabetes Sci Technol (2022). https://doi.org/10.1177/19322968221140401 ↩