Efficacy of once‐weekly insulin efsitora versus once‐daily basal insulin in type 2 diabetes: A systematic review and meta‐analysis

Abstract Aims Once‐weekly insulin efsitora is a novel basal insulin designed to maintain glycaemic control with fewer injections, potentially improving adherence. Data on its efficacy and safety remain scarce. This systematic review and meta‐analysis analysed randomized controlled trials (RCTs) comparing the efficacy and safety of once‐weekly efsitora versus once‐daily basal insulin in adults with type 2 diabetes mellitus (T2D). Materials and methods PubMed, Embase, and Scopus databases were searched up to July 6, 2025 to identify RCTs comparing once‐weekly efsitora with once‐daily basal insulin for T2D. Primary outcomes included changes in glycated haemoglobin (HbA1c), changes in fasting plasma glucose, change in total weekly insulin dose, and HbA1c target achievement. Statistical analyses were performed using Review Manager (RevMan) version 5.4, employing a random‐effects model to pool mean differences (MDs) and 95% confidence intervals (CIs), with heterogeneity assessed using the I 2 statistic. Results Seven RCTs involving 4170 participants were analysed (2347 on efsitora and 1877 on once‐daily insulin). At 26 weeks, HbA1c reduction was similar between groups (mean difference (MD) –0.02%; (−0.11 to 0.08; p = 0.74)). At 52 weeks, efsitora achieved statistically significant greater reduction in HbA1c (MD –0.12%; −0.20 to −0.03; p = 0.009) and was associated with a lower change in total weekly insulin dose (MD −30.55, (−46.48 to −14.52; p = 0.0002)). Time in the target glucose range showed a non‐significant numerical increase (MD: 1.72 (95% CI: −0.10 to 3.53; p = 0.06)), while time above range decreased (MD: –2.13 (95% CI: −4.01 to −0.25; p = 0.03)). Hypoglycaemia, serious adverse events, injection‐site reactions, and hypersensitivity events were comparable across groups, although a numerically, non‐significant increase in major adverse events with efsitora was noted, with an odds ratio of 1.22 (95% CI: 0.97–1.53; p = 0.09). Conclusions Once‐weekly insulin efsitora demonstrated comparable glycaemic efficacy and superiority in reduction of HbA1c and change in total weekly insulin dose at 52 weeks, while maintaining an acceptable safety profile. Longer‐term studies and real‐world data are warranted to further confirm sustained efficacy, safety, and cost‐effectiveness.