Insulin icodec (icodec) is a first-in-class once-weekly basal insulin approved for the treatment of adults with type 1 diabetes (T1D) and type 2 diabetes (T2D). Healthcare professionals (HCPs) may benefit from clear and practical guidance on translating the use of icodec from a controlled clinical trial setting into real-world clinical practice to ensure its appropriate implementation. Here, we primarily review the available evidence for icodec in T2D to provide evidence-based clinical recommendations and expert opinions to guide the use of icodec in a clinical setting. The pharmacology of icodec is summarized, along with an overview of the results from the ONWARDS 1-6 clinical trials (NCT04460885, NCT04770532, NCT04795531, NCT04880850, NCT04760626, NCT04848480). Key guidance on the practical use of icodec, including treatment initiation, switching to icodec from a once- or twice-daily basal insulin, switching from icodec back to a daily basal insulin, and dose titration, is provided. Icodec usage in special populations and practical situations (e.g., elderly and pediatric individuals, hepatic and renal impairment, hospitalized individuals, and those who are pregnant or planning pregnancy) is discussed. Considerations for glucose monitoring and management, as well as co-administration of icodec with other non-insulin glucose-lowering medications, are provided. Finally, we also briefly summarize the available evidence on icodec use in individuals with T1D, although the primary focus of this review is on its use in T2D. This review provides a comprehensive information resource for HCPs regarding the use of icodec in clinical practice.