Long-acting FGF21 analogs and agonists that mimic FGF21 action are under investigation in clinical trials in patients with obesity and diabetes (ClinicalTrials registration no. NCT02413372, NCT02538874, NCT2593331, NCT02708576, and NCT03060538). This evidence concerns the gene FGF21 and obesity due to melanocortin 4 receptor deficiency.