Hypoglycaemia: insulin lispro reduced the frequency of severe hypoglycaemia.

Clinical bottom line (level 1b)

  1. In patients with well controlled IDDM, use of insulin lispro reduced frequency of severe hypoglycaemic events (NNT = 9 at 12 weeks) .
  2. In patients with IDDM using insulin lispro instead of regular insulin reduced episodes of hypoglycaemic coma (NNT = 15 at 12 weeks) .
Holleman et al: Diabetes Care 1997; 20 (12): 1827-1832
Expires June 2003

The study

Unblinded ?concealed randomised cross-over trial with intention-to-treat
Setting: 19 centres across UK, Belgium and the Netherlands

199 patients (aged mean 35.4y, 63% male) insulin treated IDDM with HbA1c <150% of upper limit of normal

Excluded if
  • hypoglycaemia unawareness
  • >2 hospitalisations for hypoglycaemia in previous year


    • Control Group: (n = 199, 189 analysed): regular insulin (actrapid) before meals, and NPH insulin at night
    Experimental Group: (n = 199, 189 analysed): insulin lispro before meals with NPH insulin at night

    95% followed for 24 weeks episodes of severe hypoglycaemia (requiring the assistance of another person) and hypoglycaemic coma

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    incidence of severe hypoglycaemia 12 weeks 58
    (29.2%)    		 36
    (18.1%)    		 38%
    (10% to 57%)    		 11.1%
    (2.78% to 19.3%)    		 9
    (5 to 36)
    episodes of hypoglycaemic coma 12 weeks 16
    (8.04%)    		 3
    (1.51%)    		 81%
    (37% to 94%)    		 6.53%
    (2.39% to 10.7%)    		 15
    (9 to 42)
    number of patients who continued using regular insulin after the trial 24 weeks 44
    (22.1%)    		 144
    (72.4%)    		 -%
    (% to %)    		 -50.3%
    (-58.7% to -41.8%)    		 -2
    (-2 to -2)

  • Quality of life questionnaire also used; not a validated instrument and without full explanation of data collected.

    • Comments

    1. High number of coma events in the regular-treated group.
    2. 'Quality of life' scale used in the study is unvalidated, but ~70% of patients elected to continue using insulin lispro.

    Citation

    1. Holleman F, Schmitt H, Rottiers R, et al: Reduced frequency of severe hypoglycemia and coma in well-controlled IDDM patients treated with insulin lispro. Diabetes Care 1997; 20 (12): 1827-1832
    Contributor: Bob Phillips and Clare Wotton, Unknown Month 1999
    Reviewer:

    Clinical Question.
    Patient well-controlled IDDM
    Intervention or Exposure insulin lispro
    Outcome hypoglycaemia