Description

Technical Parameters

Introduction

peptides

product-1400-1400

Products Description

#### 1. Drug Overview

Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue and a long-acting GLP-1 receptor agonist (GLP-1 RA). It was developed by Novo Nordisk and was approved by the FDA for the treatment of type 2 diabetes in 2009. In 2014, it was expanded to obesity indications. It mimics the effects of natural GLP-1, enhances insulin secretion, inhibits glucagon release, and delays gastric emptying, thereby achieving blood sugar control and weight management.

#### 2. Structural classification and chemical characteristics

##### 1. **Molecular structure**

- **Basic structure**: Liraglutide is modified from human GLP-1 (7-37) with 97% sequence homology, containing 31 amino acids (molecular formula: C₁₇₂H₂₆₅N₄₃O₅₁, molecular weight: 3751.2 Da).

- **Key modifications**:

- **Lysine at position 26**: Connecting a 16-carbon fatty acid chain (palmitic acid), extending the side chain through a γ-glutamic acid spacer.

- **Arginine at position 34 replaces lysine**: Enhances enzymatic stability.

- **Action**: The fatty acid chain promotes binding to albumin, prolongs the half-life to 11-13 hours (natural GLP-1 is only 2 minutes), and enables once-daily subcutaneous injection.

##### 2. **Classification of similar drugs**

- **Classification based on half-life**:

- **Short-acting drugs**: such as exenatide (twice a day).

- **Long-acting drugs**: liraglutide, dulaglutide (once a week).

- **Based on structural modifications**:

- **Fatty acid chain modification** (such as liraglutide).

- **Fc fusion protein** (such as albiglutide).

- **PEGylation** (such as semaglutide).

#### 3. Pharmacological advantages and clinical benefits

##### 1. **Core advantages**

- **Long-term efficacy**: Once-daily dosing improves compliance.

- **Multi-target effects**:

- **Blood sugar control**: HbA1c is reduced by 1.0-1.5% (LEAD series of studies).

- **Weight management**: Average weight loss is 4-6kg (SCALE trial, the proportion of obese patients who lost ≥5% weight reached 63.2%).

- **Cardiovascular protection**: Reduce the risk of major cardiovascular events by 13% (LEADER trial).

- **Low risk of hypoglycemia**: Only glucose-dependent insulin secretion is promoted.

##### 2. **Side effects and safety**

- **Common reactions**: Nausea (20-30%), diarrhea (10-15%), mostly transient.

- **Contraindications**: Patients with a history or family history of medullary thyroid cancer are contraindicated (related to the potential risks of GLP-1 RA).

#### 4. Physical and chemical properties and formulation characteristics

##### 1. **Basic physical and chemical parameters**

- **Solubility**: easily soluble in water (solubility>50 mg/mL at pH 8.0), slightly soluble in ethanol.

- **Stability**:

- **pH sensitivity**: most stable at pH 7.4-8.0, easily degraded in acidic environment.

- **Temperature**: refrigerated at 2-8℃ when unopened, and can be stored at room temperature (≤30℃) for 30 days after opening.

- **Appearance**:

- **API**: white to off-white powder.

- **Injection**: transparent colorless to light yellow liquid (due to differences in concentration and excipients).

##### 2. **Preparation process**

- **Prefilled pen design**: the common dose is 6 mg/mL (1.2-1.8 mg/day for diabetes, 3.0 mg/day for obesity).

- **Excipient ingredients**: including disodium hydrogen phosphate, propylene glycol, phenol (preservative), etc., to adjust the osmotic pressure to about 290 mOsm/kg.

#### 5. Clinical application and market status

##### 1. **Indication expansion**

- **Type 2 diabetes**: as a second-line treatment after metformin (ADA/EASD consensus).

- **Obesity**: patients with BMI ≥ 30 or ≥ 27 with comorbidities (FDA approved 3.0 mg dose).

- **Potential areas in research**: non-alcoholic steatohepatitis (NASH), Alzheimer's disease (neuroprotective effect).

##### 2. **Market dynamics**

- **Original drug**: trade name Victoza (diabetes) and Saxenda (obesity), with a total sales of approximately US$3.6 billion in 2022.

- **Biosimilars**: will face competition after patent expiration (EU 2023, US 2024), and prices may drop by 30-50%.

#### 6. Future development direction

1. **Development of new dosage forms**

- **Oral preparations**: Semaglutide has successfully developed an oral version, and liraglutide may follow.

- **Sustained-release microspheres**: Achieve weekly or even monthly dosing.

2. **Structural optimization**

- **Dual-target agonists**: Such as the GLP-1/GIP dual agonist Tirzepatide (approved), which has better efficacy than single-target drugs.

- **Tissue-selective modification**: Enhance central appetite suppression or liver targeting.

3. **Combination therapy**

- **Combined with SGLT-2 inhibitors**: Synergistically improve blood sugar and cardiorenal outcomes.

- **Combined with bariatric surgery**: Improve postoperative weight maintenance effect.

#### 7. Summary

Liraglutide has become a milestone drug in the field of metabolic diseases with its unique structural design, balancing efficacy and safety. In the future, with the innovation of dosage forms and the advancement of molecular engineering, its scope of application will be further expanded, providing better solutions for hundreds of millions of patients around the world.