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As the prevalence of obesity continuous to grow, the development of new, efficacious anti-obesity pharmaceuticals becomes increasingly important. In this context, endogenous peptides with anorexigenic effects are highly interesting. However, peptides have short in vivo half-lives and, thus, half-life extension is essential for the development of anti-obesity peptide pharmaceuticals. Typically, half-life extension is ensured by attachment of peptides to macromolecules (e.g. PEG) or through lipidation, which promotes non-covalent interactions with albumin. However, alternative half-life extension strategies that can add novel properties to peptides or further increase peptide half-lives continues to be attractive. Moreover, half-life extension can affect peptide properties beyond pharmacokinetics, for example distribution, internalization, and pharmacodynamics. Such ‘secondary’ properties of half-life extenders remain relatively understudied despite their importance for peptide pharmaceuticals. This thesis aimed to expand the toolbox of half-life extenders applicable for anti-obesity peptides. For this, two avenues of research were followed. One aiming at the development of a novel half-life extending strategy, and a second aiming to expand the understanding of ‘secondary’ properties conferred to peptides by commonly applied half-life extenders. In project 1, we investigated the effect of mono- or divalent small-molecule albumin binders for half-life extension of peptides. For proof-of-principle, the clinically relevant peptide glucagon-like peptide 1 (GLP-1) was functionalized with diflunisal, indomethacin, or both. In vitro- and biophysical characterization revealed how albumin affinity was significantly increased for divalent analogues, as compared to the monovalent analogues. In lean mice, this translated to a superior biological efficacy and a promising gain in circulatory half-life and absorption time for the divalent GLP-1 analogues. Importantly, the in vivo ef