Semaglutide is a GLP-1 receptor agonist with 94% sequence homology to native human GLP-1[4]. It promotes weight loss through multiple mechanisms: reducing appetite and food intake via central nervous system effects, slowing gastric emptying, and improving glycemic control through glucose-dependent insulin secretion[1][3]. The extended half-life of approximately 7 days is due to albumin binding and resistance to DPP-4 degradation, enabling convenient once-weekly dosing[1].
Clinical trials have demonstrated significant weight loss (mean 10–15% body weight reduction) in individuals with obesity when combined with lifestyle interventions[1][5]. The weekly 2.4 mg maintenance dose is FDA-approved for chronic weight management and represents the standard clinical approach[3][4].
Observations from clinical literature and regulatory approvals[1][3][5].
Potential Benefits:
- Significant weight loss (mean 10–15% body weight reduction in clinical trials at 2.4 mg weekly dose) when combined with lifestyle modifications[1][5].
- Improved glycemic control through enhanced glucose-dependent insulin secretion and reduced glucagon secretion[3].
- Reduced appetite and food intake via central nervous system GLP-1 receptor activation[1].
- Cardiovascular benefits demonstrated in outcome trials, including reduced risk of major adverse cardiovascular events[6].
- Convenient once-weekly dosing improves adherence compared to daily regimens[1].
Potential Side Effects:
- Gastrointestinal effects (most common): nausea, vomiting, diarrhea, constipation, abdominal pain—typically mild to moderate and decreasing with gradual dose escalation[1][3].
- Injection-site reactions: redness, swelling, or irritation (generally mild and transient)[11].
- Hypoglycemia risk (when combined with insulin or sulfonylureas)—less common with semaglutide monotherapy due to glucose-dependent mechanism[3].
- Rare serious adverse events: pancreatitis, gallbladder disease, acute kidney injury; thyroid C-cell tumors observed in rodent studies (relevance to humans uncertain)[4].
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