Summary of currently available insulin analogue products
| Insulin (unit concentration) | Year of first commercial introduction | Dosing | Onset of action | Peak effect | Duration | Mechanism of acceleration/protraction | Notes |
| Mealtime insulin products | |||||||
| Regular human insulin (U100) | 1982 | 30 min before start of meal | 30–60 min | 2–4 hours | 5–8 hours | None (structurally identical to human insulin) | Slower onset and protracted action requires dosing in advance of meals, thereby reducing scope for tailoring dose to carbohydrate content |
| Insulin lispro (U100) | 1996 | 15 min before or immediately after start of meal | 15–30 min | 0.5–2 hours | ≤5 hours | Reversal of two amino acid residues in the B-chain terminus to decrease strength of self-association | |
| Insulin aspart (U100) | 1999 | 5–10 min before start of meal | 15 min | 1–3 hours | 3–5 hours | Substitution of one amino acid in the B-chain terminus (aspart for proline at position B28) to decrease strength of self-association | |
| Insulin glulisine (U100) | 2004 | Inject within 15 min before or within 20 min after start of meal | 12–30 min | 1.5 hours | ~5.3 hours | Substitution of two amino acid residues in the B-chain to decrease strength of self-association | |
| Fast-acting insulin aspart (U100) | 2017 | Inject at the start of meal, or within 20 min of starting | ~16–20 min | ~1.5–2.2 hours | ~5–7 hours | Insulin aspart with niacinamide and L-arginine to further accelerate subcutaneous absorption | Very rapid action may be advantageous in pump administration, where acceleration of absorption is demonstrated to be faster than with subcutaneous injection |
| Fast-acting insulin lispro (U100) | 2020 | At start of meal or within 20 min of starting | ~15–~17 min | ~2–3 hours | ~5–7 hours | Insulin lispro with citrate and treprostinil to further accelerate subcutaneous absorption | Very rapid action may be advantageous in pump administration |
| Basal insulin products | |||||||
| NPH insulin (Humulin N) (U100) | 1982 | Usually twice daily | 1–2 hours | 2–8 hours | 14–24 hours | Addition of protamine to the formulation results in a crystallised suspension of insulin | NPH insulin must be thoroughly resuspended prior to injection to ensure dosing accuracy. Patient failure to do this might contribute to a well-documented variability in glucose-lowering effect from injection to injection |
| Insulin glargine (U100) | 2000 | Once daily, same time each day | N/A | No pronounced peak | ~24 hours | One amino acid substitution in the A-chain and two additions to the B-chain terminus cause isoelectric precipitation after subcutaneous injection, to slow absorption | Soluble at pH 4 |
| Insulin detemir (U100) | 2004 | Once or twice daily | N/A | No pronounced peak | Up to 24 hours | Removal of terminal B-chain amino acid and acylation with a 14-carbon fatty acid chain results in an insulin that reversibly binds albumin in the depot and circulation, retarding kinetics | Detemir causes less weight gain than other insulins by mechanisms not fully understood, and it has been shown to have a relatively predictable action from dose to dose. The frequent need for twice-daily dosing due to shorter duration of action than other basal analogues has limited its uptake in T1D |
| Insulin degludec (U100 and U200) | 2013 | Once daily—dose times can be anytime of day for adults and the same time every day for paediatric patients, but should be a minimum of 8 hours apart | N/A | No pronounced peak | 42 hours | Removal of terminal B-chain amino acid and acylation with a 16-carbon fatty diacid results in an insulin that forms multihexamer chains in the depot and reversibly binds albumin in the circulation, retarding kinetics | Degludec has a half-life of 25 hours. This means that, at steady-state, it has a very low peak:trough ratio, hence a very predictable and near-flat action profile |
| Insulin glargine (U300) | 2015 | Once daily at the same time each day | ~6 hours | No pronounced peak | 10.8–>24 hours | When formulated at a three-times-greater molar concentration than the original formulation, the absorption of the insulin glargine precipitate is further retarded | U300 glargine has a flatter and more predictable PK/PD effect than U100 glargine, but up to 20% lower molar potency, possibly due to increased subcutaneous metabolism with its slower dissolution |
Human soluble insulin and NPH insulin (not analogues) are included as comparators to illustrate how the pharmacokinetic properties of the analogues represent improvements. Information derived from Hirsch et al26 and manufacturers’ labels.
N/A, not applicable; NPH, neutral protamine Hagedorn; PD, pharmacodynamic; PK, pharmacokinetic; T1D, type 1 diabetes.