Liraglutide

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Cat Number

API0232951

CAS Number

204656-20-2

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CAS Number

204656-20-2

EINECS

810-818-7

Synonyms

NN2211, Saxenda, victoza

Molecular Formula

C172H265N43O51

Molecular Weight

3751

Smiles

CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC6=CN=CN6)N)C(=O)O

General Description

Liraglutide is a synthetic analog of human glucagon-like peptide-1 (GLP-1) and a GLP-1 receptor agonist, administered via once-daily subcutaneous injection. Structurally, it shares 97% homology with human GLP-1 and is designed to resist rapid degradation by dipeptidyl peptidase-4, extending its half-life for once-daily dosing.

Mechanism of Action

Liraglutide activates GLP-1 receptors in a glucose-dependent manner, stimulating insulin secretion from pancreatic beta cells and suppressing glucagon release to lower blood glucose. It slows gastric emptying and reduces appetite through direct action on GLP-1 receptors in the brain, particularly in the lateral septum and hypothalamus, promoting early satiety and reduced caloric intake. Additionally, central liraglutide action may promote pancreatic beta-cell proliferation via vagal pathways originating in the brainstem.

Application

Liraglutide is FDA-approved to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes, as an adjunct to diet and exercise. Beyond glycemic and weight effects, liraglutide provides cardiovascular benefits by reducing major adverse cardiovascular events and slows progression of diabetic kidney disease in high-risk patients.

Maselli D, et al. investigated the effects of subcutaneous liraglutide (escalated to 3 mg daily) on weight loss and gastrointestinal function in 136 adults with obesity. Compared to placebo, liraglutide significantly increased weight loss at 5 and 16 weeks, slowed gastric emptying of solids (half-time), and increased fasting gastric volume and satiation. Importantly, the degree of gastric emptying delay was positively correlated with weight loss during liraglutide treatment. Pharmacogenomic analysis revealed that specific polymorphisms in GLP1R (rs6923761) and TCF7L2 (rs7903146) were associated with differential treatment responses, including reduced body fat percentage and lower achieved body weight.

Fig. 1 Study design and gastric function testing in 136 participants over a 16-week period. (Maselli D, et al., 2022)

References

Maselli D, et al. Effects of liraglutide on gastrointestinal functions and weight in obesity: A randomized clinical and pharmacogenomic trial. Obesity (Silver Spring). 2022;30(8):1608-1620.

Rubino DM, et al. randomized 338 adults with overweight or obesity to receive once-weekly semaglutide 2.4 mg or once-daily liraglutide 3.0 mg, combined with diet and physical activity. Mean weight change was –15.8% with semaglutide versus –6.4% with liraglutide (difference, –9.4 percentage points; P < 0.001), with significantly greater odds of achieving 10%, 15%, and 20% weight loss with semaglutide. Gastrointestinal adverse events occurred at similar rates in both groups (84.1% vs. 82.7%).

Fig. 2 Percentage change in body weight from baseline to week 68 (observed in-trial data; full analysis set). (Rubino DM, et al, 2022)

References

Rubino DM, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022;327(2):138-150.

Does Liraglutide require strict cold chain storage and transport?

Yes, as a peptide, it is thermally labile. It must be stored and shipped at 2-8°C. We use validated cold chain packaging with continuous temperature monitoring for every shipment.

Is Liraglutide prone to aggregation during freeze-thaw cycles?

Absolutely. Freeze-thaw cycling can cause aggregation and loss of biological activity. We strongly advise against freezing and recommend consistent refrigerated storage without fluctuation.

What is the stability of Liraglutide after reconstitution in injection pens?

Once formulated, it has limited stability. We provide detailed stability data for in-use conditions, typically allowing 30 days of use under refrigeration after first puncture.

How is the purity of Liraglutide confirmed given its peptide nature?

We use a combination of reverse-phase HPLC for chemical purity, SEC-HPLC for aggregates, and mass spectrometry for identity, ensuring batch-to-batch consistency.