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reported that cleavage products derived from GLP-1 reduced tubulointerstitial renal damage, lowered the expression of tubular injury markers, and attenuated the renal accumulation of macrophages and T cells (Moellmann et al., 2018)
Genetic and physiological insights into satiation variability predict responses to obesity treatment
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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