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Some patients report fatigue during tirzepatide treatment, particularly during the early treatment phase or with dose escalation, though this is not among the most common adverse events in clinical trials
This approach is especially relevant for patients who arent significantly overweight but carry metabolic inflammation
The 28.7% figure for retatrutide comes from TRIUMPH-4, a Phase 3 trial of 445 adults living with obesity and knee osteoarthritis, reported by Lilly in a December 2025 press release
The research showed that Sema influences not only homeostatic hunger circuits but also hedonic pathways associated with reward-based eating
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