Glucagon antagonists are provided which comprise amino acid substitutions and/or chemical modifications to glucagon sequence. In one embodiment, the glucagon antagonists comprise a native glucagon peptide that has been modified by the deletion of the first two to five amino acid residues from the N-terminus and (i) an amino acid substitution at position 9 (according to the numbering of native glucagon) or (ii) substitution of the Phe at position 6 (according to the numbering of native glucagon) with phenyl lactic acid (PLA). In another embodiment, the glucagon antagonists comprise the structure A-B-C as described herein, wherein A is PLA, an oxy derivative thereof, or a peptide of 2-6 amino acids in which two consecutive amino acids of the peptide are linked via an ester or ether bond.
