Orforglipron (OFG), an oral, once daily, non-peptide GLP-1 receptor agonist, demonstrated effective weight loss of up to − 10.1 kg at 26 weeks in T2D, and up to − 15.4 kg at 36 weeks in participants with obesity without T2D [25, 26]. This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.