Semaglutide

Semaglutide is a 31-amino-acid GLP-1 receptor agonist with two substitutions (Aib8 and Arg34) and a C-18 fatty di-acid that drives albumin binding. The result is enzymatic resistance to DPP-4 and a circulating half-life of about 1 week. Activation of pancreatic β-cell GLP-1 receptors increases glucose-dependent insulin release; central receptors in the arcuate nucleus reduce hunger and food reward signalling.

Half-life: ≈ 7 days

• Average weight loss 14.9% over 68 weeks at 2.4 mg weekly (STEP-1)
• HbA1c reduction up to 1.8 percentage points
• Cardiovascular event reduction in adults with established CV disease (SELECT)
• Improved markers of fatty liver disease
• Reduction of food cravings and binge episodes

Standard escalation: 0.25 mg weekly x 4 weeks → 0.5 mg x 4 → 1.0 mg x 4 → 1.7 mg x 4 → 2.4 mg maintenance. Subcutaneous injection in abdomen, thigh, or upper arm, rotating sites.

Dosing information is summarised from published clinical and pre-clinical literature for research purposes only and does not constitute medical advice.

• STEP-1: Once-weekly semaglutide in adults with overweight or obesity

  New England Journal of Medicine · 2021

  1 961 participants achieved a mean weight loss of 14.9% vs 2.4% on placebo at 68 weeks.

• SELECT: Semaglutide and cardiovascular outcomes in obesity without diabetes

  New England Journal of Medicine · 2023

  20% relative risk reduction in MACE over a mean 40 months in 17 604 patients with prior CV disease.

• Gastrointestinal effects (nausea, reflux, constipation) are dose-related and usually transient
• Black-box warning for medullary thyroid C-cell tumours in rodent models
• Avoid in history of pancreatitis, gallbladder disease, severe gastroparesis
• Holding the dose at the previous tier is preferable to escalating through intolerable nausea

For research use. Consult a licensed clinician before any human application. Not for use in pregnancy, lactation, or active malignancy without specialist supervision.