Targeted exome sequencing of six genes encoding drug targets for obesity or T2DM in 11,806 individuals with well-defined metabolic traits, followed by targeted genotyping of 39,979 individuals, reported an association of GLP1R rs10305492 (Ala316Thr) with lower fasting glucose and T2D risk. This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.