Semaglutide (CAS 910463-68-2) is a synthetic GLP-1 (Glucagon-Like Peptide-1) analogue composed of 31 amino acids with two key modifications: Aib substitution at position 8 (α-aminoisobutyric acid, a non-natural amino acid resistant to DPP-4 cleavage) and acylation of Lys26 by a C18 fatty acid (stearodiglutamic acid) via a γ-Glu-2×OEG linker. This dual modification confers strong binding to serum albumin (>99%) and a remarkable ~165-hour plasma half-life (≈ 7 days), enabling once-weekly administration.
Mechanism of action. Semaglutide acts as selective agonist of the GLP-1R receptor (class B1 GPCR, Gαs coupling → adenylate cyclase → cAMP → PKA → CREB). Activation stimulates glucose-dependent insulin secretion by pancreatic β-cells, inhibits glucagon secretion by α-cells, slows gastric emptying, and acts on hypothalamic nuclei (arcuate, paraventricular) to reduce food intake via POMC/CART neuron regulation and AgRP/NPY neuron inhibition.
Human clinical status. Under brand names Ozempic®, Rybelsus® (oral) and Wegovy® (weight management), semaglutide is approved by the FDA (2017, 2019, 2021) and EMA for type 2 diabetes and obesity (BMI ≥ 30 or ≥ 27 with comorbidity). Pivotal STEP (Semaglutide Treatment Effect in People with Obesity) and SUSTAIN trials demonstrated 14.9% mean weight loss over 68 weeks at 2.4 mg/week, and 1.5-2.0% HbA1c reduction.
Research use. Laboratories use semaglutide in preclinical investigations: DIO (Diet-Induced Obesity), db/db and ob/ob mouse models for diabetes, neuroinflammation studies (Alzheimer and Parkinson models), cardio-renal trials and liver studies (NAFLD/NASH). At lab-peptides-france.com, semaglutide is marketed as RUO with an HPLC ≥ 98% specification, in 5mg, 10mg and 20mg doses to cover dose-ranging protocols.
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Structure, mécanisme amyline, récepteur CTR + RAMP1/2/3, pharmacocinétique, programme REDEFINE (CagriSema), comparaison versus pramlintide Symlin, synergie GLP-1, protocoles de reconstitution RUO, stabilité et perspectives. Le pilier scientifique de référence sur le cagrilintide.
Structure, mécanisme triple agoniste, pharmacocinétique, programme TRIUMPH (1-4, Obesity, HFpEF, MASH), comparaison versus semaglutide et tirzepatide, protocoles de reconstitution RUO, stabilité et perspectives réglementaires. Le pilier scientifique de référence sur le retatrutide.