Existing candidates for treating non-alc. steatohepatitis (NASH), including glucagon-like peptide-1 (GLP-1) analogs and previous GLP-1/glucagon receptor (GLP-1R/GCGR) dual agonists, do not address the need for substantial weight loss adequately. We sought a more effective, evenly balanced GLP-1/GCGR dual agonist suitable for weekly administration. We studied a new class of covalent modifiers, glycolipid surfactants, to prolong the duration of action of candidate peptides. Variation of the hydrophobic tail of such surfactant modifications resulted in a wide and tunable range of phys. properties and t1/2 values. We selected compound 17, which demonstrated high, evenly balanced potency for activation of human GLP-1R and GCGRs, return of diet induced obese (DIO) rodents to lean body/liver weight and prolonged duration correlated with high serum albumin binding. We observed a prolonged pharmacodynamic (PD) profile in rodents and pharmacokinetics (PK) in mini-pigs (t1/2 = 52 h, mean residence time, MRT = 84 h), suggesting suitability for weekly dosing. Accordingly, 17 (ALT-801) was selected for clin. development.