An Obesity Subphenotype With Low Endogenous GLP-1 Production Shows Markedly Greater Weight Loss With Tirzepatide

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A multicohort study in adults with obesity identified a distinct subgroup characterized by fast solid-meal gastric emptying, greater postprandial hunger, and unexpectedly low postprandial GLP-1 levels.

This phenotype, termed discordant gastric emptying/GLP-1 (dc-GE/GLP-1), also showed lower circulating PYY and CCK and reduced colonic mucosal expression of GCG and PYY, supporting impaired enteroendocrine hormone synthesis rather than simply altered hormone release.

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