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GLP-1 modulates actin polymerization, improving insulin sensitivity and glucose-stimulated insulin secretion Chronic hyperglycemia, or glucotoxicity, causes pancreatic cell dysfunction, diminished glucose-stimulated insulin secretion, and the production of long actin stress fibers 6,7

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Patients should understand the potential downsides before starting treatment

Additionally, semaglutide can make you tired due to its gastrointestinal side effects, including nausea, vomiting, and diarrhea.[1-3] How tired you feel while taking semaglutide is also impacted by how you take semaglutide (pill or injection) and your dosage.[1-3] How You Take Semaglutide Can Affect How Tired You Feel Semaglutide is available as a daily pill (Rybelsus) or a once-weekly injection (Ozempic and Wegovy).[1-3] During clinical trials, individuals taking semaglutide as an injection were more likely to report fatigue (tiredness) as a side effect.[1-3] Patients taking Rybelsus during clinical trials did not report fatigue as a side effect.[2] Those taking 14 mg of Rybelsus did report nausea (20%), abdominal pain (11%), diarrhea (10%), decreased appetite (9%), vomiting (8%), and constipation (5%).[2] During clinical trials for Ozempic and Wegovy (semaglutide injections), patients did report feeling tired.[1,3] 11% of participants taking 2.4 mg of Wegovy for weight management reported feeling tired.[3] Less than .4% of patients reported feeling tired as a side effect during clinical trials for Ozempic.[1] Those taking 1 mg of Ozempic did report nausea (20.3%), vomiting (9.2%), diarrhea (8.8%), abdominal pain (5.7%), and constipation (3.1%).[1] Your Dose Can Affect How Tired You Feel Individuals taking a higher dose of semaglutide are more likely to feel tired.[1-3] Wegovy for weight management offers the maximum dose of semaglutide (2.4 mg) and is associated with a higher incidence of fatigue and other side effects.[1-3] Individuals taking 2.4 mg of Wegovy reported nausea (44%), diarrhea (30%), vomiting (24%), constipation (24%), abdominal pain (20%), and abdominal distension (bloating)(7%) as side effects.[3] Wegovy is available as a pre-filled, single-dose injection pen containing 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, or 2.4 mg of semaglutide.[3] Clinical experience suggests starting on a low dose of semaglutide and slowly increasing the dosage may reduce the risk of side effects.[4] Patients can start with 0.25 mg and increase their dose every four weeks until they reach the maintenance dose (2.4 mg).[3] Consult your healthcare provider if you experience fatigue or other side effects while taking semaglutide