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In the STEP and SURMOUNT trials for semaglutide and tirzepatide respectively, weight loss curves generally began to flatten between weeks 36 and 60, reflecting the physiological set point adaptation that occurs as appetite suppression becomes partially offset by metabolic adaptation

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therefore, the proposed link between PGC‑1α/TFAM suppression, mitochondrial uncoupling, and ATP deficiency remains inferential and need future work to directly assess mitochondrial membrane potential, mitochondrial ROS, and ATP levels in sperm and testicular cells to confirm the contribution of mitochondrial bioenergetic failure to PS‑MP‑induced sperm dysfunction