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Unlike the large synthetic molecule semaglutide, orforglipron is a small molecule, though both act by mimicking GLP-1

(3) gut-brain signaling via the vagus nerve, with downstream anti-inflammatory effects that could influence behavior indirectly

Among hypoglycemic drugs, sulfonylureas secretagogues and glinide secretagogues can increase the risk of skeletal muscle atrophy, metformin may have adverse effects on skeletal muscle mitochondrial function, and sodium-glucose transporter 2 inhibitors (SGLT2i) increase the risk of sarcopenia [13]

Bedossa P, et al

Its possible the medication was working before, but over time what we call tolerance can develop, and it may no longer have the same effect, Dr

Veljaca et al., 2003