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1991;261(2 Pt 2):R501-507
This difference reflects the brain's adaptation to new satiety patterns over time
Furthermore, as Kumar points out, there's simply a lack of research to say whether these products are safe or effective long-term, especially in the context of weight loss
What that wisdom missed - and what a small group of academic endocrinologists, most prominently Richard DiMarchi's group at Indiana University, had begun to argue aggressively through the early 2010s - was that glucagon's metabolic role is not just "raise glucose." It is a broader lever on hepatic lipid handling, mitochondrial uncoupling, brown-fat activation, and energy expenditure
The addition of GIPR activity was the key pharmacological innovation of tirzepatide, enabling greater weight loss than pure GLP-1 agonism
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