Apelin receptor agonism improves symptoms of metabolic syndrome. However, endogenous apelin peptides have short half-lives, making their utility as potential drugs limited. Previously, we had identified a novel pyrazole-based agonist scaffold. Systematic modification of this scaffold was performed to produce compounds with improved ADME properties. Compound <b>13</b> with favorable agonist potency (cAMPi EC<sub>50</sub> = 162 nM), human liver microsome stability (<i>T</i><sub>1/2</sub> = 62 min), and pharmacokinetic profile in rodents was identified. The compound was tested in a mouse model of diet-induced obesity (DIO) and metabolic syndrome for efficacy. Treatment with <b>13</b> led to significant weight loss, hypophagia, improved glucose utilization, reduced liver steatosis, and improvement of disease-associated biomarkers. In conclusion, a small-molecule agonist of the apelin receptor has been identified that is suitable for <i>in vivo</i> investigation of the apelinergic system in DIO and perhaps other diseases where this receptor has been implicated to play a role.