A comparison of ultra-rapid and rapid insulin in automated insulin delivery for type 1 diabetes: A systematic review and meta-analysis of randomized controlled trials

Aims This study aimed to summarize and compare the evidence on the efficacy and safety of automated insulin delivery (AID) systems using ultra-rapid-acting insulin analogues (URAIs), such as fast-acting insulin aspart (FIASP) and ultra-rapid lispro (URLi) (referred to as AID-URAIs), versus those using rapid-acting insulin analogues (RAIs) (referred to as AID-RAIs) in patients with type 1 diabetes (T1D). Materials and Methods We conducted a systematic review and meta-analysis of AID-URAI versus AID-RAI. We systematically searched PubMed, Scopus, ProQuest, Web of Science, Cochrane Library, Clinicaltrial.gov, and medRxiv for articles up to 30 October 2024. Percent time-in-range (TIR; 3.9-10 mmol/L), time-below-range (TBR; 3.9- and 3.0-mmol/L), and time-above-range (TAR; >10.0- and 13.9-mmol/L) were extracted. This study was registered in the PROSPERO (CRD42024602279). Results Sixteen randomized controlled trials (664 participants) were included in this study. AID-URAI were associated with an increased percentage of TIR, but not clinically significant (pooled mean difference {MD} = 1.07% [95% confidence interval {CI}: 0.11 to 2.02]; I-2 = 0%; p = 0.029; high certainty). The favourable effect was consistent in AID systems incorporating automated bolus correction, adults, study duration >4 weeks, and FIASP subgroups. AID-URAI has a 0.35% lower percentage of TBR (<3.9 mmol/L) compared with AID-RAI. There were no significant differences in the risk of diabetic ketoacidosis and severe hypoglycemia between the two groups. Conclusions AID-URAI slightly improves the percentage of TIR and has a good safety profile without increasing the risk of diabetic ketoacidosis and severe hypoglycemia.