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Fatigue on semaglutide usually comes from one or more of three sources: reduced caloric intake, B12 or other nutrient deficiencies, or dehydration

LDL receptor upregulation: Some studies suggest glucagon signaling may enhance LDL receptor activity , increasing clearance of LDL particles from circulation

Ustundag S, Sen S, Yalcin O, Ciftci S, Demirkan B, Ture M

Some patients may experience loss of lean mass alongside fat loss, which could theoretically contribute to feelings of weakness or achiness, particularly if protein intake is inadequate

Vilsboll T, Agerso H, Krarup T, Holst JJ (2003)

Occasional vomiting once or twice in the first week at a new dose does not necessarily mean tirzepatide needs to be stopped