Stanford-Led Genome Medicine Study: PAM Enzyme Variants in ~10% of People May Blunt GLP-1 Glycemic Response
A Stanford-led study published March 29 in Genome Medicine, with broad media coverage in late April, identifies two genetic variants that handicap the PAM enzyme (peptidyl-glycine alpha-amidating monooxygenase) responsible for activating GLP-1 and other peptide hormones. In a meta-analysis of three trials with 1,119 participants, carriers — roughly 10% of the general population — were less responsive to GLP-1 drugs and saw smaller HbA1c reductions despite higher circulating GLP-1 levels. The work is the first in-depth investigation of a 'GLP-1 resistance' phenotype, sits alongside the recent 23andMe GLP1R/GIPR variant paper, and opens a path toward genetically-stratified incretin prescribing.