Once-weekly insulin icodec versus once-daily long-acting insulins for type 2 diabetes mellitus: Systematic review and meta-analysis.

ABSTRACT

Background: Insulin icodec is a novel, long-acting, once-weekly basal insulin analog. Its comparative efficacy and safety with basal once-daily insulins in type 2 diabetes mellittus is uncertain. Objective: Evaluate potential efficacy, benefits and risks associated with icodec compared to once-daily basal insulin analogs (degludec or glargine). Methods: We systematically searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) published until June 2023 comparing icodec versus long-acting insulin analogs (degludec and glargine) in type 2 diabetes mellitus (T2DM) with at least 12 weeks of follow-up. Binary endpoints were assessed with risk ratios (RRs) and continuous endpoints were compared using mean differences (MDs), with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023452468). Results: A total of seven RCTs and 3286 patients with T2DM were included, of whom 1509 (60.6%) received icodec treatment. The follow-up period ranged from 16 to 78 weeks. Compared with once-daily basal insulin analogs, icodec led to a greater improvement in HbA1c (MD -0.15%; 95% CI -0.21, -0.10; p < 0.0001; I2 = 0%) and time in range (TIR) (MD 2.83%; 95%CI 0.94; 4.71; p = 0.003; I2 = 22%). Body weight was increased with icodec treatment (MD 0.78 Kg; 95%CI 0.42, 1.15; p < 0.01; I2 = 86%). There was also a higher rate of injection site reactions (RR 1.89; 95%CI 1.12, 3.18; p = 0.016; I2 = 0%) and nasopharyngitis (RR 1.94; 95%CI 1.11, 3.38; p = 0.020; I2 = 0%) in the icodec group, compared with once-daily regimens. There was no significant difference between groups in fasting plasma glucose. Conclusions: In this meta-analysis of RCTs, insulin icodec led to better control of HbA1c and TIR as compared with once-daily insulin regimens, albeit with increased weight gain and a higher rate of injection site reaction in the Icodec group.