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.

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 :