Systematic review and meta-analysis of RCTs evaluating once-weekly insulin formulations in T2DM (through June 2025, incorporating five new 2025 trials), reporting pooled HbA1c reduction, fasting plasma glucose, weight, and hypoglycemia outcomes. Contextualizes once-weekly insulins as an alternative therapeutic category alongside semaglutide for T2DM management. Provides a comprehensive evidence synthesis for the emerging once-weekly insulin class—informing clinicians about insulin alternatives to GLP-1 RAs that offer reduced injection frequency while maintaining glycemic efficacy.
Abstract
AIMS: Once-weekly (OW) insulins represent a promising strategy to reduce injection burden and improve adherence in type 2 diabetes management. This meta-analysis aimed to quantify pooled effect sizes for key biological and clinical outcomes, integrating new findings from the five large trials published in 2025.
MATERIALS AND METHODS: We systematically searched PubMed, WoS, ClinicalTrials.gov and EU Clinical Trials databases up to June 2025 for randomized controlled trials (RCTs) evaluating OW insulins in type 2 diabetes. Primary outcomes included efficacy (HbA1c, fasting plasma glucose (FPG), time-in-range (TIR), time-above-range) and safety outcomes (body weight, hypoglycaemia, time-below-range). Data were analysed using both frequentist and Bayesian approaches.
RESULTS: Among 435 screened records, 16 RCTs were included. OW insulins achieved a greater reduction in HbA1c compared to once-daily insulin or semaglutide (pooled mean difference: -0.12%, 95% CI: -0.19 to -0.04, p = 0.007). TIR was significantly longer in the OW insulin group (+2.41% of total time, 95% CI: 1.13 to 3.69, p = 0.002), while FPG changes were comparable (-3.37 mg/dL, 95% CI: -7.95 to 1.21 mg/dL, p = 0.14). Body weight changes were generally similar, but excluding trials using IcoSema revealed a modest weight gain (+0.33 kg, 95% CI: 0.04 to 0.62, p = 0.030). The incidence of clinically significant or severe hypoglycaemia did not differ between groups (pooled incidence rate ratio: 1.04, 95% CI: 0.79 to 1.28, p = 0.75). Meta-regression confirmed consistent effect sizes across OW insulin types, treatment durations and prior insulin regimens.
CONCLUSIONS: OW insulins modestly improve glycaemic control without increasing hypoglycaemia risk, though slight weight gain may occur.