Overview of in vitro assays demonstrating that insulin icodec has retained the same biological effects as human insulin
| HSA (%) | EC50 (nM) Mean (95% CI)* | EC50 (%) Insulin icodec relative to human insulin Mean (95% CI) | |||
| Insulin icodec | Human insulin | ||||
| Metabolic effects | |||||
| Lipogenesis in rat adipocytes | 0.1 | n=4 | 135 (113 to 160) | 0.041 (0.037 to 0.046) | 0.029 (0.026 to 0.032) |
| Glycogen accumulation in rat hepatocytes | 0 | n=7 | 6.4 (4.2 to 9.7) | 0.28 (0.18 to 0.44) | 4.3 (3.5 to 5.3) |
| 0.1 | n=8 | 69 (37 to 130) | 0.17 (0.11 to 0.26) | 0.24 (0.11 to 0.51) | |
| Glycogen synthesis in rat L6-hIR cells | 0.1 | n=4 | 8.53 (5.73 to 12.69) | 0.05 (0.02 to 0.10) | 0.52 (0.35 to 0.79) |
| Glycogen synthesis in human MCF-7 cells | 0 | n=5 | 4863 (1571 to 15 050) | 12.2 (3.8 to 39.0) | 0.26 (0.11 to 0.62) |
| Mitogenic effects | |||||
| DNA synthesis in rat L6-hIR cells | 0 | n=5 | 20.2 (14.6 to 28.0) | 0.13 (0.05 to 0.32) | 0.6 (0.3 to 1.0) |
| DNA synthesis in human MCF-7 cells | 0 | n=4 | 625 (140 to 2790) | 2.8 (1.5 to 5.4) | 0.5 (0.1 to 2.1) |
| DNA synthesis in human COLO-205 cells | 0 | n=3 | 73 (53 to 100) | 1.4 (0.2 to 12.7) | 2.0 (0.3 to 12.9) |
| DNA synthesis in human HMEC cells | 0 | n=7 | 1879 (1340 to 2633) | 3.7 (2.6 to 5.3) | 0.2 (0.1 to 0.3) |
*Geometric mean for all assays.
COLO-205, human colon adenocarcinoma cells; EC50, half maximal effective concentration; hIR, human insulin receptor; HMEC, primary human mammary epithelial cells; HSA, human serum albumin; L6-hIR, rat skeletal myoblast cells over-expressing hIR; MCF-7, human mammary adenocarcinoma cells.