Once-weekly insulin as novel treatment for type 2 diabetes mellitus: A systematic review and meta-analysis of randomized clinical trials

Aims: The primary objective of this investigation is to examine the efficacy and safety of once-weekly insulin formulation when compared to regular basal insulin for the management of type 2 diabetes mellitus (T2DM). Methods: A comprehensive search was conducted on the Cochrane Library, Scopus, ClinicalTrials.gov, and Medline databases up until August 19th, 2023. This review incorporates literature that examines the comparison between once-weekly insulin and basal insulin. The risk of bias was assessed by using RoB v2 tool from Cochrane Collaborations. We employed random-effect models to analyze the mean difference (MD) and odds ratio (OR) for presentation of the outcomes. Results: A total of nine trials with 3963 participants were incorporated. Five included trials had "low-risk" of bias, whereas the remaining four trials had "some-concern" risk of bias due to protocol deviations from intended intervention. The results of our meta-analysis showed higher reduction of HbA1c levels in the once-weekly insulin group when compared to regular basal insulin (MD -0.12 %; 95 %CI: -0.20, -0.04, p = 0.003, I2 = 60 %). The fasting plasma glucose (FPG) and body weight change from baseline did not differ significantly between two groups. Meanwhile, the total adverse events (TAEs) were shown to be higher in the once-weekly insulin; however, the serious AEs (SAEs) and clinically significant hypoglycemia did not differ significantly between onceweekly insulin and these active controls. Conclusions: This study suggests better efficacy and similar safety of insulin icodec when compared to regular basal insulin. Our study also suggests similar efficacy and safety between insulin efsitora alfa (BIF) and regular basal insulin. Further clinical trials are still needed to confirm the results of our study. Registration details: CRD42023453635.