Liraglutide Tablet affects metabolism by activating GLP-1 receptors and regulating the cAMP PKA pathway, such as activating AMPK signaling to improve energy metabolism and inhibit cell apoptosis. It can promote insulin synthesis and secretion, inhibit glucagon secretion, stimulate beta cell proliferation and regeneration, and inhibit beta cell apoptosis, thereby exerting a hypoglycemic effect. In addition, Liraglutide can delay gastric emptying, reduce food intake, reduce patient weight, improve blood lipid and blood pressure control, and also have neuroprotective effects on nerve and myocardial cells.
Products Description
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Liraglutide COA
Liraglutide Tablet is a GLP-1 receptor agonist, chemically named Arg34 Lys26- (N - ε - (γ - Glu (N - α - hexadecanoyl)) - GLP-1 [7-37], with a molecular formula of C172H265N43O51, and a molecular weight of 3751.20 Da. Its structure is a peptide chain containing 31 amino acids, with the core feature being that the 26th lysine side chain is linked to a C16 palmitoyl group via a glutamic acid spacer. This fatty acid modification can enhance binding with albumin. Extend the half-life in the body to 13 hours and achieve once daily administration. The mainstream preparation techniques for Liraglutide API can be divided into two categories: solid-phase peptide synthesis (SPPS, chemical method) and genetic engineering recombinant expression (biological method).
Solid phase synthesis core process
Solid phase carrier: 2-Chlorotriphenylmethyl chloride resin (2-CTC resin) is preferred, with a substitution degree of 0.4-0.6 mmol/g, characterized by low resistance, easy cracking, and minimal side reactions.
Protecting amino acids: adopting N-terminal Fmoc protection and side chain acid sensitive protection strategies:
Conventional amino acids: Fmoc Ala OH, Fmoc Gly OH, Fmoc Thr (tBu) - OH, etc;
Key modified amino acid: Fmoc Lys (N - ε - (N - α - palmitoyl-L - γ - Glu (Boc)) - OH, directly introduced into the fatty acid side chain to reduce post modification side reactions.
Solid phase assembly of polypeptide chains (31 amino acid coupling cycles)
Resin loading: Fmoc Gly OH was coupled with 2-CTC resin under the catalysis of * * DIEA (diisopropylethylamine) * *, and reacted at room temperature for 2 hours. The reaction endpoint was detected by the indene ketone method, and the unreacted sites were blocked with methanol.
Fmoc removal: Add 20% piperidine/DMF solution, stir at room temperature for 15 minutes, repeat twice, thoroughly remove the N-terminal Fmoc protecting group, and expose the free amino group.
Amino acid coupling: using DIEA+TBTU condensation system (molar ratio 2:1), protecting amino acids and resin amino groups are fed in a ratio of 1.5-2.0:1, DMF is used as the solvent, and the reaction is carried out at room temperature for 100-140 minutes; After each coupling step, wash alternately with DMF and DCM 6 times to remove unreacted raw materials.
Loop extension: Repeat the "deprotection coupling washing" cycle according to the sequence of Liraglutide (His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Tyr Leu Glu Gly Gln Ala Ala Lys (palmitoyl Glu) Glu Phe Ile Trp Leu Val Arg Gly Arg Gly OH) until complete sequence assembly.
Cracking and side chain deprotection
Cracking liquid system: TFA: EDT: PhSMe: TIS: H ₂ O=85:5:4:2:4 (volume ratio), TFA as the main cracking agent, EDT and PhSMe as free radical scavengers, inhibiting the oxidation of tryptophan and tyrosine.
Cracking conditions: Mix peptide resin and lysis buffer in a ratio of 1g: 10mL, stir at room temperature for 2.5 hours; Filter the resin, add pre cooled anhydrous ether (1:10 volume ratio) to the filtrate, and let it stand for 2 hours to settle the crude peptide.
Crude peptide collection: Centrifuge (4000 rpm, 10 minutes) to discard the supernatant, wash the precipitate with ether three times, vacuum dry the crude Deliaglutide product, with a purity of about 75-85%.
Purification and freeze-drying of raw materials
Chromatographic conditions: C18 reverse phase column (particle size 10 μ m, pore size 120 Å), mobile phase A: 0.1% TFA aqueous solution, B: 0.1% TFA acetonitrile solution; Gradient elution (5% → 60% B, 30 minutes), flow rate 80-100 mL/min, detection wavelength 220 nm.
Step by step collection: Extract the main peak component (purity>98%), remove the front and back peaks containing impurities; Combine the pure components and concentrate under reduced pressure (35 ℃, vacuum degree 0.08 MPa) to remove acetonitrile.
Desalination and Freeze Drying
Desalination: Ultrafiltration membrane (molecular weight cutoff of 3000 Da) is used, and pure water is dialyzed three times to remove TFA and inorganic salts; Concentrate to a concentration of 1-3 mg/mL and filter finely with a 0.45 μ m membrane.
Freeze drying process:
Pre freezing: Pre freeze at -45 ℃ for 3 hours to form uniform ice crystals;
Sublimation drying: Gradient heating (-45 ℃ → -20 ℃ → 0 ℃), vacuum degree of 15 Pa, maintained for 15 hours, to remove free water;
Analysis of drying: Maintain at 25 ℃ for 12 hours, control moisture content<1.0%;
Endpoint: Obtain white loose Liraglutide API powder with purity>99.0% and single impurity<0.5%.
Reference information source:
- A solid-phase synthesis method of liraglutide (CN107033112B);
- Method for preparing liraglutide by solid-liquid combination (CN105111303B);
- Technical Specification for Solid Phase Synthesis of Peptide Drugs (2022 Edition).
As a chronic metabolic disease, the core bottleneck of long-term management of obesity lies in high recurrence rate and long-term compliance. Liraglutide Tablet, as an important dosage form of GLP-1 receptor agonist (GLP-1 RA), has evolved to achieve long-term weight maintenance and metabolic improvement in overweight individuals through a triple mechanism of central appetite regulation, gastrointestinal motility inhibition, and metabolic remodeling.
The recurrence rate is extremely high: after simple lifestyle intervention, the weight rebound rate within one year can reach 30% to 50%. Traditional weight loss drugs have poor tolerance and limited efficacy, making it difficult to break through the "weight loss rebound" cycle.
Shortboard of compliance: Although injectable forms (such as 3.0 mg subcutaneous injection) have clear therapeutic effects, daily/weekly injections lead to long-term compliance of less than 40%, becoming the main obstacle to long-term management.
Metabolic comorbidity superposition: Overweight individuals often have insulin resistance, hypertension, and dyslipidemia, requiring multi-target regulatory drugs rather than simply weight loss.
Development and clinical positioning of oral Liraglutide preparations
Formulation Evolution: Liraglutide oral formulation breaks through the bottleneck of peptide oral absorption through technologies such as nanomicelles and enteric carriers, and its bioavailability is 4-13 times higher than unmodified formulations, achieving once daily oral administration.
Core positioning: As a first-line drug choice for long-term weight management of overweight, it combines the advantages of weight loss, improving metabolism, and enhancing compliance, filling the compliance gap of injectable formulations and meeting the long-term management needs of chronic obesity.
Reference information source:
- Expert consensus on clinical application of enteropancreatin based weight loss drugs (2025 version) Chinese Journal of diabetes, 2025
- Quinapanta Castro, et al. Corrected: Efficacy of Liraglutide for Weight Loss in Overweight and Obese Non-diabetic Adults. Cureus, 2025.
- Lilly's oral GLP-1, orforglipron, demonstrated meaningful weight loss. NEJM, 2025.
- National Medical Products Administration Drug Review Center. Guidelines for Clinical Trial Design of Liraglutide for Weight Management, 2022
Pharmacokinetics and mechanism of action of oral Liraglutide preparations
Pharmacokinetic characteristics: oral absorption and long-term efficacy
| Characteristic parameter | Specific data | Clinical significance |
| Bioavailability | Optimized formula reaches 5% to 10% (4-13 times higher than unmodified dosage form) | Ensure effective blood drug concentration for oral administration and avoid injection dependence |
| Peak time | Peak concentration (Cmax) reached 2-4 hours after oral administration | Synchronize with postprandial appetite peak, accurately suppress eating impulse |
| Half-life | Approximately 12-18 hours, administered once daily to maintain a steady state for 24 hours | Realize long-term regulation, reduce medication frequency, and improve compliance |
| Absorption site | Mainly absorbed through the upper segment of the small intestine, and protected by enteric carriers for molecular degradation | Avoiding stomach acid and enzymatic hydrolysis to ensure drug activity |
| Metabolic pathway | Mainly degraded by proteases, with a small amount excreted through the kidneys | Patients with liver and kidney dysfunction need to adjust the dosage, and the safety is controllable |
The Triple Core Mechanism of Long term Weight Management
1. Central nervous system regulation: Suppressing appetite from the root
Oral Liraglutide Tablet penetrates the blood-brain barrier, activates GLP-1 receptors in the hypothalamic arcuate nucleus (ARC), upregulates opioid peptide melanocortinogen (POMC) (appetite suppressant), and downregulates neuropeptide Y (NPY)/agouti associated protein (AgRP) (appetite promoting).
Long term activation can reshape the sensitivity of the appetite center, reduce baseline appetite levels, decrease "binge eating" behavior, and achieve negative balance of long-term energy intake.
2. Gastrointestinal motility regulation: delaying emptying and increasing satiety
Inhibit gastric emptying rate by 30%~50%, prolong the residence time of food in the gastrointestinal tract, enhance the stimulation of gastric wall tension receptors, and increase satiety.
Slow down small intestinal peristalsis, promote nutrient absorption feedback, reduce ghrelin secretion, and prolong the duration of satiety (from 2-3 hours to 6-8 hours).
3. Metabolic remodeling: improving insulin resistance and fat breakdown
Activate peripheral tissue GLP-1 receptors, enhance insulin sensitivity (improve peripheral tissue insulin resistance by 20%~30%), and reduce fat accumulation.
Promote lipolysis of adipose tissue, inhibit fat synthesis, reduce visceral fat content (visceral fat reduction of 15%~25%), and improve metabolic disorders.
Inhibit glucagon secretion, reduce hepatic glucose output, synergistically reduce weight loss, and lower the risk of metabolic comorbidities.
Reference information source:
- Liraglutide activates key brain circuits to trigger weight loss in obesity. News-Medical, 2024.
- An oral liraglutide nanomicelle formulation conferring reduced insulin-resistance. PubMed, 2025.
- Effects of Liraglutide on Gastrointestinal Functions and Weight in Obesity. PMC, 2025.
- Chinese Journal of Endocrinology and Metabolism The metabolic regulation mechanism of GLP-1 receptor agonists in obese individuals, 2024
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