Background: Diabetes Mellitus management continues to evolve with innovations in insulin therapy aimed at improving efficacy and patient comfort. Purpose: This study aims to compare the efficacy and safety of Insulin Efsitora Alfa and Insulin Icodec in the management of Diabetes Mellitus. Methods: This scoping review analyzed articles published between August 2020 and August 2025 from PubMed, ScienceDirect, and other sources. Inclusion criteria included English-language observational studies addressing the efficacy and safety of both insulins in DM. Ten articles were selected after a rigorous screening process. Results: Both insulins demonstrated non-inferior efficacy in lowering HbA1c compared to daily basal insulin, with pharmacokinetic/pharmacodynamic profiles favoring once-weekly dosing. General tolerability was good, and Time in Range (TIR) was comparable. However, Insulin Icodec was associated with a higher incidence of hypoglycemia, especially in type 1 diabetes, compared to Insulin Efsitora Alfa which showed similar hypoglycemia rates to daily insulin. Patient satisfaction with Icodec was higher in type 2 diabetes, but lower in type 1. Implications: Both insulins offer the potential to improve patient adherence. Insulin Efsitora Alfa may be more suitable for patients prone to hypoglycemia. The increased risk of hypoglycemia with Insulin Icodec requires careful clinical consideration and dose titration. Further head-to-head comparison studies are needed to guide optimal therapy.