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Very rapidly-acting insulin

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

  • insulin analogues - designed to provide a more physiological insulin profile around meals
  • mealtime insulins
    • rapid-acting insulin analogues general features (1,2)
      • rapid onset of action of approximately 15 mins
      • duration of action about 2–5 hours
      • can be injected immediately before or just after meals e.g. lispro, aspart, glulisine
  • quicker onset of action and shorter duration time than short-acting insulins such as human actrapid. Short - acting insulins have a tendency to form hexamers in the insulin vials and so have a relatively slow onset of action
  • types:
    • insulin lispro (Humalog) - identical amino acid structure to human insulin apart from the inversion of lysine and proline residues at B28 and B29
      • peak action after about 1 hour; duration of action 2-5 hours (insulin lispro)
    • insulin aspart (NovoRapid) - identical structure to human insulin apart from the replacement of proline at B28 with aspartic acid
      • insulin aspart is licensed for the treatment of patients with diabetes - no studies of the drug have been performed in children aged under 6 years (1)
        • the summary of product characteristics (SPC) recommends that it is injected subcutaneously "generally" immediately before a meal, but also that it can be given soon after the meal, when necessary
          • also recommends that insulin aspart should "normally" be used in combination with an intermediate- or long-acting insulin given at least once a day.
          • has a faster onset (10-20 minutes) and shorter duration (3-5 hours) of action than does soluble human insulin, with a maximum effect at 1-3 hours after injection
  • insulin analogues facilitate a much more flexible insulin regimen - can be injected immediately before meals, less postprandial hypoglycaemia, there can be a more sensitive adjustment to match food intake at a particular time
    • a systematic review (3) concluded that:
      • compared with the use of conventional human insulin, use of the analogues was associated with a small decrease in HbA1c levels in patients with type 1 diabetes (weighted mean difference [WMD] -0.12%, 95% CI -0.17% to -0.07%) but not type 2 diabetes (WMD -0.02%, 95% CI -0.1% to 0.07%)
      • use of an analogue did not reduce the overall frequency of hypoglycaemia compared with human insulin, either in patients with type 1 diabetes (WMD of episodes/patient/month -0.2, 95% CI -1.2 to 0.9 ) or those with type 2 diabetes (-0.2, 95% CI -0.5 to 0.1
        • severe hypoglycaemia however occurred less often with the analogues than with human insulin
          • considering first type 1 diabetes
            • the median incidence (number of episodes/100 person-years) with the analogues was 20.3 (range 0-247.3) and with human insulin 37.2 (range 0-544)
          • considering type 2 diabetes
            • the median incidence with the analogues was 0.6 (range 0-30.3) and with human insulin 2.8 (range 0-50.4)
      • the authors reviewers felt unable to carry out a meta-analysis on the data on nocturnal hypoglycaemia

Fast-acting insulin aspart (Fiasp) is the first insulin of its class and was approved by the FDA in September 2017

  • more rapid absorption and action of aspart insulin is achieved by altering the excipients in the aqueous solution: L-arginine for stabilization of the insulin molecule in solution and niacinamide for more rapid absorption
    • results in a faster initial absorption of insulin compared to NovoRapid(R) (which only contains insulin aspart)

Lispro (Humalog (R)) is a commercially available, rapid-acting human insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus

  • ultra-rapid lispro (URLi) (Lyumjev (R)) developed insulin lispro formulation utilizing two key enabling excipients, treprostinil and citrate, with independent mechanisms to accelerate the absorption of insulin lispro


  1. Drug and Therapeutics Bulletin (2004); 42(10):77-80.
  2. MeRec Bulletin 2007;17(4).
  3. Siebenhofer A et al. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus (Cochrane Review). In: The Cochrane Library, Issue 3, 2004.
  4. Nally LM, Sherr JL, Van Name MA, Patel AD, Tamborlane WV. Pharmacologic treatment options for type 1 diabetes: what's new?. Expert Rev Clin Pharmacol. 2019;12(5):471-479. doi:10.1080/17512433.2019.1597705

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