A method for the avoidance of side effects associated with glucagon-like peptide-1 receptor (GLP-1R) agonists through vitamin B12 conjugation prior to administration. Vitamin B12 may be bound to a GLP-1R agonist, such as exendin-4 (Ex4), to provide enhanced proteolytic stability while retaining GLP-1R agonism. The conjugate (B12-Ex4) also improves glucose tolerance without producing anorexia and malaise. A GLP-1R agonist that is resistant to DPP-IV degradation and does not penetrate readily into the CNS, but retains the enhanced pharmacokinetic and pharmacodynamic profile on pancreatic β-cells provide a pharmacological tool for glycemic control in type 2 diabetes mellitus (T2DM) patients without eliciting unwanted hypophagia and nausea.
