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Menopausal women typically continue HRT for symptom management regardless of weight

Hauguel S, Challier JC, Cedard L, Olive G (1983) Metabolism of the human placenta perfused in vitro: glucose transfer and utilization, O2 consumption, lactate and ammonia production

2 Since it is non-peptide, orforglipron avoids GI degradation barriers that limit peptides, thereby enabling once-daily administration while maintaining efficacy on glucose control, body weight, and tolerability

The third is duration and safety : short controlled studies in animals say almost nothing about what months or years of exposure would do in a human, which is precisely why the cycling section defaults to scheduled off periods rather than open-ended use