Abstract

Background: Once‐daily basal insulin is widely used in the management of type 2 diabetes, but poor adherence to daily injections often impairs glycaemic control. Once‐weekly efsitora alfa may overcome these limitations, but pooled data assessing its comparative efficacy and safety remain limited. Methods: PubMed/MEDLINE, Google Scholar, and the Cochrane Library were searched up to July 2025 for RCTs comparing once‐weekly efsitora with once daily insulin in adults with T2D. Weighted mean differences (MDs), odds ratios (ORs), and risk ratios (RRs) were pooled using a random‐effects model, and results were reported with 95% confidence intervals. Results: Six RCTs comprising 3967 participants were included. There were no significant differences between once‐weekly efsitora and daily insulin in change in HbA1c (MD –0.04; 95% CI –0.10 to 0.02; p = 0.15), change in fasting plasma glucose (MD 1.94 mg/dL; 95% CI –2.98 to 6.86; p = 0.44), proportion of patients achieving HbA1c < 7%, change in body weight, or time below range. Efsitora was associated with an increase in time in range (MD 0.80 percentage points; 95% CI 0.09 to 1.52; p = 0.03) and a reduction in time above range (MD –1.45 percentage points; 95% CI –2.87 to −0.02; p = 0.05). The risk of treatment‐emergent adverse events (TEAEs) was higher with efsitora (RR 1.13; 95% CI 1.05 to 1.20; p = 0.0004), whereas serious adverse events, hypersensitivity reactions, injection‐site reactions, and hypoglycaemia events were comparable between the two groups. Conclusion: Once‐weekly efsitora provides comparable glycaemic control and improved time‐in‐range compared to daily insulin, although with a higher rate of TEAEs.