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Importantly, GIP receptor sensitivity is impaired in prolonged hyperglycemic states due to receptor downregulation but can be restored upon achieving euglycemia through complementary GLP-1 action [38,39]

Discontinuation of GLP-1 therapy may result in weight regain and recurrence of hepatic steatosis, emphasizing the need for long-term treatment strategies

For patients, the implications are far-reaching

While these outcomes are based on large clinical trials (STEP 1 and SURMOUNT-1), weight loss should still be approached with realistic expectations, personalized goals, and ongoing support

We also discuss the metabolic actions of insulin-like peptide 5, a recently characterized gut hormone that are co-secreted with GLP-1 and PYY