The present disclosure provides cells engineered to express recombinantly manufactured ultra-long acting insulin-Fc fusion proteins for use in treating diabetes. The insulin-Fc fusion proteins comprise an insulin polypeptide linked via a peptide linker to an Fc-fragment of human origin. Exemplary ultra-long acting insulin-Fc fusion proteins, cells engineered to express the fusion proteins, polynucleotides encoding these insulin-Fc fusion proteins, and pharmaceutical formulations of exemplary insulin-Fc fusion proteins are provided, in addition to methods of use and preparation.