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Retatrutide adds a third mechanism, glucagon receptor activation, and in Phase 3 trials has demonstrated approximately 28% average body weight reduction over 18 months, compared to tirzepatides 22.5% in its own Phase 3 programme [1][2]

However, chronic low intake combined with rapid weight loss may increase long-term bone turnover risk if nutritional adequacy is not maintained

By week 8-12 of consistent therapy, most patients report that diarrhea resolves or becomes infrequent, even at therapeutic doses

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4.2 Non-weight-dependent (direct) mechanism PYY acts on the pancreas to protect -cell function and regulate insulin secretion