Insulin icodec is a novel once-weekly basal insulin analog subcutaneous injection seeking approval by the United States Food and Drug Administration (FDA) for use in both type 1 and type 2 diabetes mellitus. The mission of this manuscript is to provide a thorough overview of insulin icodec’s clinical trials that were involved in its approval as well as review its pharmacology, pharmacokinetics, adverse effects, drug interactions, dosage recommendations, and regulatory issues. This article includes a thorough review of insulin icodec’s safety and efficacy in type 1 and type 2 diabetes mellitus including its pharmacokinetic and pharmacodynamic profile. A systematic search of the electronic database of PubMed from inception until December 2024 using MeSH keywords was completed. Keywords used were icodec, insulin, type 1 diabetes, and type 2 diabetes. Overall, 14 clinical trials were identified and reviewed. The majority of the trials reviewed showed decreases in A1C as primary endpoints and non-inferiority and superiority with insulin icodec versus the comparator. In select studies, mild hypoglycemia was more evident in subjects taking insulin icodec versus the comparator but no other concerns were identified. The reviewed literature showed similar and sometimes improved glycemic control when insulin icodec was compared to other long-acting insulins both in insulin-naive and previously insulin-treated patients. Hypoglycemia was similar or slightly increased with insulin icodec when compared to other long acting insulins. Overall, icodec is a useful, new formulation of basal insulin that allows for less injections, improved compliance, and potentially improved glycemic control providing a new tool to practitioners managing patients with diabetes who need to be on insulin.