Highlights hESC-derived PECs in a prevascularized device-less site routinely reverse diabetes Device-less PEC grafts functioned better than fat pad and subcutaneous PEC grafts Human C-peptide secretion was glucose regulated in device-less PEC grafts Safely retrieved grafts stained positive for insulin, glucagon, and somatostatin Summary Beta-cell replacement therapy is an effective means to restore glucose homeostasis...