Network meta-analysis protocol outlines comparison of ultra-short-acting insulin analogues for Type 1 Diabetes

For individuals with Type 1 Diabetes Mellitus (T1DM) on multiple daily injections, achieving optimal glycaemic control while minimizing hypoglycaemia remains a significant challenge. While various (ultra-)short-acting insulin analogues exist, their relative efficacy and safety compared to regular human insulin and each other are not fully established. Current treatment guidelines often lack definitive comparative data, leaving clinicians and patients to navigate a complex landscape of options without a clear, evidence-based ranking of these critical medications.

Researchers designed a network meta-analysis protocol to compare (ultra-)short-acting insulin analogues to regular human insulin in adults with Type 1 Diabetes on multiple daily injections. They searched CENTRAL, MEDLINE, Web of Science, WHO ICTRP, and ClinicalTrials.gov up to May 14, 2025. Eligibility criteria included randomized controlled trials (RCTs) with an intervention duration of at least 24 weeks, comparing analogues like insulin aspart, lispro, glulisine, ultra-rapid lispro (URLi), and fast-acting insulin aspart (FIAsp). Primary outcomes included glycaemic control (HbA1c), hypoglycaemia incidence, diabetic ketoacidosis, quality of life, and adherence to treatment. Statistical analyses will employ a frequentist network meta-analysis, using regular human insulin as the reference, with a random-effects model for other outcomes and pairwise comparisons.

The systematic search identified and included 15 RCTs involving a total of 6335 participants for analysis. These trials evaluated the comparative effects of insulin aspart, lispro, glulisine, ultra-rapid lispro (URLi), and fast-acting insulin aspart (FIAsp). The intervention durations across the included studies ranged from 24 to 52 weeks, providing long-term data for comparison. Participants in the included trials had a mean age of 36.4 years and an average baseline HbA1c of 8.1%, indicating a representative adult Type 1 Diabetes population. The protocol outlines a robust methodology to synthesize these data, aiming to provide a comprehensive ranking of these insulin analogues based on critical outcomes. > The meta-analysis will specifically compare these analogues against regular human insulin and each other across key metrics like glycaemic control, hypoglycaemia rates, and quality of life, using the CINeMA framework to rate evidence certainty.