Study designs of evaluations included in the review
Randomised controlled trials (RCTs) comparing the incidence of severe hypoglycaemia in type 1 diabetics during insulin lispro therapy and during soluble insulin therapy. The trials were included if they measured hypoglycaemia using a standard hypoglycaemia questionnaire, they enrolled at least 50 patients, and were of at least 2 months' duration. Both parallel and crossover trial designs were included. The duration of the studies was 1 year for the parallel group, and ranged from 4 to 8 months for the crossover studies. Double-blind and open trials were also included. Acute pharmacokinetic trials, case reports, and smaller studies with different objectives or the lack of a control group treated with human soluble insulin, were excluded. The included studies had a formal protocol and each used standardised case report forms. The case report forms, and methods for the collection and storage of the data, were similar across the trials.
Specific interventions included in the review
Insulin lispro and regular human insulin, including Humulin Regular (Eli Lilly) and Actrapid (Novo Nordisk). Basal insulin included isophane insulin NPH or ultralente (Eli Lilly). Rapid acting insulin (insulin lispro or human soluble insulin) was injected into the subcutaneous tissue of the abdomen from 45 to 15 minutes before each meal. The insulin doses and dietary instructions were adjusted, based on glucose self-monitoring and the metabolic needs of the patient. The glycaemic targets were fasting blood glucose values of less than 7.8 mmol/L without hypoglycaemia, and maintenance of 2-hour post-prandial glucose values of less than 10 mmol/L.
Participants included in the review
Type I diabetes. The participants included adults, newly diagnosed adults, and adolescents with type I diabetes. Patients with a history of recurrent severe hypoglycaemia were excluded.
Outcomes assessed in the review
The primary outcome was the number of hypoglycaemic episodes defined as coma or requiring glucagon or intravenous glucose. The haemoglobin (Hb)A1c level at the end point of the study was also assessed.
How were decisions on the relevance of primary studies made?
The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.