Once-Weekly Subcutaneous Insulin Efsitora for the Management of Diabetes Mellitus: A Systematic Review and Meta-Analysis Study

Even though insulin therapy is the cornerstone of diabetes mellitus management, multiple daily injections are associated with poor adherence. Once-weekly basal insulin therapy has emerged as a novel therapeutic approach and is being evaluated in multiple ongoing clinical trials. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of once-weekly insulin efsitora therapy compared with once-daily basal insulin therapy in patients with type 1 or type 2 diabetes mellitus. Primary endpoints include glycemic control, assessed via HbA1c reduction, and hypoglycemia, classified as level 1 (54-69 mg/dL), level 2 (<54 mg/dl), or level 3 (any hypoglycemic episode characterized by altered mental and/or physical functioning requiring assistance). We have performed a systematic review and meta-analysis through an extensive literature search of major databases including Scopus, PubMed/Medline, and Cochrane databases, and have only included randomized controlled trials. We have included 5 randomized controlled trials comprising a total of 2,562 patients: 1,358 (53%) in the insulin efsitora arm and 1,204 (47%) in the insulin degludec arm. Our data show that insulin efsitora therapy achieved a similar HbA1c reduction overall (estimated treatment difference (ETD) 0.08%, 95% CI -0.01 to 0.17; I² = 42.6%), in patients with type 1 diabetes mellitus (ETD 0.10%, 95% CI -0.64-0.85; I² =24.0%) and in patients with type 2 diabetes mellitus (ETD 0.05%, 95% CI -0.25 - 0.26; I² = 38.1%) compared with insulin degludec therapy. Moreover, no statistically significant differences were identified in overall hypoglycemic events, level 2 or 3 hypoglycemic episodes, or nocturnal hypoglycemia, irrespective of diabetes mellitus subtype. Our meta-analysis shows no statistically significant difference between once-weekly insulin efsitora therapy and insulin degludec therapy in terms of glycemic control and hypoglycemic events.