The effects of PEGylation of glucose-dependent insulinotropic polypeptide (GIP) on potency and dipeptidyl peptidase IV (DPPIV) stability are reported. N-terminal modification of GIP(1-30) with 40 kDa polyethylene glycol (PEG) abrogates functional activity. In contrast, C-terminal PEGylation of GIP(1-30) maintains full agonism and reasonable potency at the GIP receptor and confers a high level of DPPIV resistance. Moreover, the dual modification of N-terminal palmitoylation and C-terminal PEGylation results in a full agonist of comparable potency to native GIP that is stable to DPPIV cleavage. The results provide the basis for the development of long acting, PEGylated GIP, GIP variants, or GIP-based hybrid peptide therapeutics.