very rapidly-acting insulin

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  • 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

Reference:

  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.

Last reviewed 01/2018

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