Table 1

Summary of currently available insulin analogue products

(unit concentration)
Year of first commercial introductionDosingOnset of actionPeak effectDurationMechanism of acceleration/protractionNotes
Mealtime insulin products
Regular human insulin (U100)198230 min before start of meal30–60 min2–4 hours5–8 hoursNone (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
199615 min before or immediately after start of meal15–30 min0.5–2 hours≤5 hoursReversal of two amino acid residues in the B-chain terminus to decrease strength of self-association
Insulin aspart
19995–10 min before start of meal15 min1–3 hours3–5 hoursSubstitution of one amino acid in the B-chain terminus (aspart for proline at position B28) to decrease strength of self-association
Insulin glulisine
2004Inject within 15 min before or within 20 min after start of meal12–30 min1.5 hours~5.3 hoursSubstitution of two amino acid residues in the B-chain to decrease strength of self-association
Fast-acting insulin aspart
2017Inject at the start of meal, or within 20 min of starting~16–20 min~1.5–2.2 hours~5–7 hoursInsulin aspart with niacinamide and L-arginine to further accelerate subcutaneous absorptionVery 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
2020At start of meal or within 20 min of starting~15–~17 min~2–3 hours~5–7 hoursInsulin lispro with citrate and treprostinil to further accelerate subcutaneous absorptionVery rapid action may be advantageous in pump administration
Basal insulin products
NPH insulin (Humulin N)
1982Usually twice daily1–2 hours2–8 hours14–24 hoursAddition of protamine to the formulation results in a crystallised suspension of insulinNPH 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
2000Once daily, same time each dayN/ANo pronounced peak~24 hoursOne amino acid substitution in the A-chain and two additions to the B-chain terminus cause isoelectric precipitation after subcutaneous injection, to slow absorptionSoluble at pH 4
Insulin detemir
2004Once or twice dailyN/ANo pronounced peakUp to 24 hoursRemoval 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 kineticsDetemir 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)
2013Once 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 apartN/ANo pronounced peak42 hoursRemoval 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 kineticsDegludec 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)2015Once daily at the same time each day~6 hoursNo pronounced peak10.8–>24 hoursWhen formulated at a three-times-greater molar concentration than the original formulation, the absorption of the insulin glargine precipitate is further retardedU300 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.