Ultra-Rapid Acting Insulin Formulations

Introduction to Ultra-Rapid Acting Insulin Formulations

Ultra-rapid acting insulins are mealtime insulins reformulated so the insulin gets into the bloodstream within minutes of an injection. The two we found in U.S. labeling are Fiasp from Novo Nordisk and Lyumjev from Eli Lilly [1][2]. Here's what surprised us when we read the prescribing information: both labels call the product a "rapid-acting human insulin analog" [1][2]. "Ultra rapid" is the name researchers use for these formulations [5], not a separate FDA category.

Innovation and Patents

The change is in the solution around the insulin, not in the insulin molecule. Fiasp is a new formulation of insulin aspart, tested in its main trial against conventional insulin aspart [4]. Its inactive ingredients include niacinamide (a form of vitamin B3) and L-arginine [1]. Lyumjev is a formulation of insulin lispro, tested against standard lispro [5], with treprostinil sodium and sodium citrate among its inactive ingredients [2]. The FDA approved Fiasp for adults on September 29, 2017 [3]. Lyumjev's label lists its initial U.S. approval as 2020 [2]. We didn't find a primary source listing the patents on either formulation, so we haven't summarized them here.

Manufacturers and Product Lines

Novo Nordisk and Eli Lilly each make one of the two products we found, and both labels cover adults and children with diabetes [1][2].

• Fiasp (Insulin Aspart) by Novo Nordisk: first approved for adults in 2017 [3]. Its label also covers use in insulin pumps and tells users to check the pump's user manual to see whether Fiasp can be used with it [1].
• Lyumjev (Insulin Lispro-aabc) by Eli Lilly: sold in two strengths, U-100 (100 units per mL) and the more concentrated U-200 [2].

Product Comparison

The labels report timing from clamp studies. In a clamp, glucose is infused to hold blood sugar steady, so the infusion rate shows how hard the insulin is working at each moment. In adults with type 1 diabetes, Fiasp's insulin showed up in the blood about 2.5 minutes after injection [1]. Across the doses tested, its first measurable glucose-lowering effect came at about 16 to 20 minutes, the peak at about 91 to 133 minutes, and the effect faded back to baseline after about 5 to 7 hours [1].

Lyumjev's label reports insulin in circulation about 1 minute after injection [2]. Its timing study, run in healthy volunteers, found a first measurable effect at about 15 to 17 minutes and a peak at about 120 to 174 minutes, with the effect returning to baseline after about 4.6 to 7.3 hours [2]. These two sets of figures come from different studies, in different people, at different doses. They describe each product; they aren't a head-to-head comparison.

The pivotal trials compared each product with the insulin it was built from. In the 26-week onset 1 trial in adults with type 1 diabetes, mealtime Fiasp was noninferior to conventional insulin aspart on HbA1c (a lab measure of average glucose over about three months), with a small additional reduction of 0.15 percentage points, and produced smaller glucose rises 1 and 2 hours after a test meal [4]. PRONTO-T1D found the same pattern for Lyumjev against lispro: HbA1c was noninferior, and the 1- and 2-hour post-meal rises were smaller [5]. Whether either insulin suits someone's routine is a decision to make with their care team.

Pitfalls, Warnings, and Issues

Faster insulin still carries the main risk of every insulin. Both labels list hypoglycemia (low blood sugar) as the most common adverse reaction, and both note that the risk is generally highest when the insulin's glucose-lowering effect peaks [1][2]. In Fiasp's pediatric trial, children using it reported more blood glucose-confirmed hypoglycemic episodes than children using NovoLog, with a bigger gap overnight [1].

Lyumjev has a warning of its own. Its label describes injection and infusion site reactions such as rash, redness, pain and itching, and notes that two of its inactive ingredients, treprostinil and sodium citrate, have been linked to site reactions with other products [2]. In PRONTO-T1D, 2.9% of people on mealtime Lyumjev reported injection site reactions, against 0.2% on lispro [5].

We looked for evidence that these insulins trigger more immune reactions than older insulins and didn't find it in the labeling. Both labels report that many trial participants had anti-insulin antibodies, often already present before the study began. Neither label identified a clinically significant effect of those antibodies on safety or effectiveness [1][2]. Cost is harder to pin down: what a pen or vial costs out of pocket depends on the insurance plan.

Conclusion

These products change how fast insulin arrives, not what the insulin is. In the trials we read, that speed meant smaller glucose rises after meals with HbA1c results similar to the older insulins [4][5]. Those trials ran for 26 weeks, so they say little about longer use. For how faster insulins interact with pump algorithms, see our page on ultra-rapid acting insulins and AID performance. Switching insulins is a decision to make with your care team.