Abstract: We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the insulin analogue, insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Our analysis suggests only a minor benefit of short-acting insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of short acting insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

Plain-language summary: We found nine randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) comparing the insulin analogues, insulin lispro and insulin aspart, to regular human insulin delivered to 2693 participants. The people in the included studies were monitored (called follow-up) for between 24 and 52 weeks. This evidence is up-to-date as of 15 April 2015. According to our analysis, short-acting insulin analogues were slightly better than regular human insulin regarding long-term glycaemic control (where blood glucose is at controlled levels) and showed similar episodes of low blood sugar (called hypoglycaemia), especially with regard to severe (night-time) hypoglycaemia. We found no information on late diabetes complications such as problems with the eyes, kidneys or feet. The studies did not report costs and they were too short to investigate death from any cause reliably. We also found no clear evidence for a marked effect of insulin analogues on the health-related quality of life (which is physical, mental, emotional and social health). The quality of the included studies was low or very low, mainly because none of the studies was carried out in a blinded way (where healthcare professionals and participants do not know which treatment they received) so that risk of bias, especially for outcomes such as hypoglycaemic episodes, was present in all of the studies. Furthermore, several studies showed inconsistencies in the reporting of methods and results.