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Semaglutide-related fatigue primarily occurs due to dramatically reduced calorie intake as appetite suppresses, rapid weight loss causing metabolic adjustments, possible dehydration from eating and drinking less, inadequate protein consumption leading to muscle loss, blood sugar changes particularly in people with diabetes, and possible sleep disruptions

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Gastric emptying returns to normal speed, eliminating the prolonged satiety that helped reduce caloric intake

A synthetic version of exendin-4 now called exenatide proved effective in diabetic mice, then in humans, and received FDA approval in 2005 under the brand name Byetta

Beyond visible changes, patients often report higher energy, better sleep, and improved blood sugar control