Skip to content

Modeling the activity of the long-acting agonists

While the activity of mealtime insulins has been well studied and modeled, mathematical models are missing for long-acting insulin agonists. Based on clamp studies in T1D, the intra-individual day-to-day variation is an important factor affecting the predictability of a single repeated dose. Moreover, the inter-individual variability makes modeling even more a challenge. Even with the best curve-fitting tools, no “global model” was achieved.

In addition to detemir (Levemir®) and glargine U100 (Lantus®, Abasaglar®), new long-acting insulin agonists degludec (Tresiba®) and glargine U300 (Toujeo®) have been added.


Using bi-exponential models

The activity of detemir and glargine U100 depend on the absolute amount (units), but also on the dose in relation to the patient's weight (U/kg). Also, the peak of action is achieved at different timepoints. The DIA of detemir is more variable and dose-dependent than that of glargine.

Bi-exponential models

For detemir, the duration of action is 14h + (24* dose/weight), and the peak is at duration/3.

For glargine U100, the duration of action is 22h + (12* dose/weight), and the peak is at duration/2.5.

For glargine U300, the duration of action is 24 + (14* dose/weight), and the peak is at duration/2.5.

For degludec, the duration is 42, with a peak at 14h after injection.

models 3

Here are some activity curves as depicted in many publications. Notice that the curve colours are different, and some of the activity curves seem to derived from steady-state euglycemic clamps, not from single injection clamps :

nature