Once-Weekly Insulin Versus Once-Daily Insulin for Type 1 Diabetes Treatment: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Background Type 1 diabetes mellitus (T1DM) represents a considerable global health burden, affecting approximately 5%-10% of individuals with diabetes. Once-weekly basal insulin could substantially reduce the number of injections for T1DM patients from 365 daily to 52 weekly doses annually. Therefore, this meta-analysis compares the safety and efficacy of once-weekly insulin formulations. Methods The systematic review and meta-analysis included the relevant randomised controlled trials (RCTs) retrieved from PubMed, EMBASE, Web of Science, Cochrane, and SCOPUS databases until September 2024. The meta-analysis was performed using (RevMan 5.4.1). The study protocol was registered on PROSPERO (CRD42024603022). Results Three RCTs comprising 1724 participants were included. Once-daily insulin significantly decreased glycated haemoglobin (HbA1c) compared to once-weekly insulin (estimated treatment difference: 0.09%, 95% CI [0.07, 0.11], p < 0.00001). Fasting blood glucose levels were comparable between the once-weekly and once-daily insulin groups (estimated treatment difference: 0.44 mg/dL, 95% CI [-0.64, 1.52], p = 0.42). Once-weekly insulin was associated with a significant increase in the incidence of injection site reactions (RR: 3.48 with 95% CI [1.30, 9.31], p = 0.01), serious adverse events (RR: 1.55 with 95% CI [1.09, 2.19], p = 0.01), and treatment-emergent adverse events (RR: 1.12 with 95% CI [1.02, 1.23], p = 0.02), while no significant difference was observed in hypersensitivity reactions (RR: 1.04 with 95% CI [0.78, 1.38], p = 0.79). Results Three RCTs comprising 1724 participants were included. Once-daily insulin significantly decreased glycated haemoglobin (HbA1c) compared to once-weekly insulin (estimated treatment difference: 0.09%, 95% CI [0.07, 0.11], p < 0.00001). Fasting blood glucose levels were comparable between the once-weekly and once-daily insulin groups (estimated treatment difference: 0.44 mg/dL, 95% CI [-0.64, 1.52], p = 0.42). Once-weekly insulin was associated with a significant increase in the incidence of injection site reactions (RR: 3.48 with 95% CI [1.30, 9.31], p = 0.01), serious adverse events (RR: 1.55 with 95% CI [1.09, 2.19], p = 0.01), and treatment-emergent adverse events (RR: 1.12 with 95% CI [1.02, 1.23], p = 0.02), while no significant difference was observed in hypersensitivity reactions (RR: 1.04 with 95% CI [0.78, 1.38], p = 0.79). Conclusion Once-daily insulin has demonstrated slightly superior HbA1c reduction, while once-weekly insulin offers potential advantages in patient adherence. However, these benefits must be weighed against an increased risk of injection site reactions and nocturnal hypoglycemia. Although once-weekly insulin is more convenient, treatment decisions should consider individual patient factors such as hypoglycemia risk and tolerance to injection reactions.