GLP-1 receptor agonists, originally developed and approved for the treatment of type 2 diabetes, have been increasingly used for weight loss by individuals without diabetes. As well, continuing research is discovering and investigating other potential applications in other areas such as cardiovascular health, neurogenerative diseases, or in treating obstructive sleep apnea, chronic kidney disease, cancer, and addiction.[1]
How It Works
First, some definitions and descriptions. GLP-1 stands for “glucagon-like peptide-1.” Peptides are molecules of two or more amino acids linked in a chain to form proteins. GLP-1 is a naturally occurring hormone in our bodies that’s released after eating. It helps to regulate blood sugar by stimulating the release of insulin from the pancreas and helps to regulate appetite by slowing the emptying of the stomach and increasing feelings of fullness.
A GLP-1 agonist mimics the effects of the natural GLP-1 hormone to regulate blood sugar and appetite. Agonists stimulate the GLP-1 receptor to increase insulin release and decrease glucagon. (Glucagon increases blood sugar level, while insulin decreases it.)
A GLP-1 receptor antagonist binds to the same receptor but inhibits the GLP-1 receptor, blocking stimulation by the GLP-1 hormone. The GLP-1 antagonist suppresses insulin secretion, and increases glucagon release, which is useful to prevent hypoglycemia.
The Research
Research on GLP-1 agonists is conducted in both academic and commercial laboratories. The research typically focuses on their therapeutic potential in metabolic disorders such as type 2 diabetes and obesity, among other emerging applications. These studies encompass various stages, including the characterization of therapeutic peptides, peptide synthesis, pharmacokinetics, and bioanalytical assessments.[2]
Common Types of Testing Conducted:
- Peptide Characterization: Involves sequence verification, purity assessment, and analysis of post-translational modifications to ensure therapeutic efficacy.
- Bioanalytical Studies: Focus on the quantification of GLP-1 and related biomarkers in various matrices, aiding in pharmacokinetic and pharmacodynamic evaluations.
- Pharmacokinetic Modeling: Includes traditional compartmental and population PK models to predict drug behavior in biological systems.
- In Vivo Screening: Conducted to assess the efficacy and safety profiles of GLP-1 receptor antagonists in animal models.
Laboratory Equipment and Analytical Techniques:
- High-Performance Liquid Chromatography (HPLC) with UV Detection: Used for assessing peptide purity and quantifying concentrations. Paired with an MS detector, a UHPLC system such as the Agilent 1290 Infinity is well-suited to GLP-1 analysis.
- Mass Spectrometry (MS): Employed for sequence confirmation, impurity identification, and post-translational modification analysis.
- Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS): Utilized for bioanalysis of biomarkers related to GLP-1 analogues, offering high specificity and selectivity. One study employed an AB Sciex API Q-Trap 5500 mass spectrometer paired with a Waters Acquity UPLC system for quantification.
- Enzyme-Linked Immunosorbent Assay (ELISA) Kits: Various kits are available for quantifying GLP-1 levels in biological samples.
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Sources & Further Reading:
[1] 7 Indications for GLP-1s Beyond Weight Loss
[3] Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs) | NIH
- Antidiabetics – GLP-1 Agonists | Washington State Health Care Authority
- GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects | Frontiers in Endocrinology
- Case Study: How Altasciences Overcame Pharmacological Challenges in a GLP-1 IND-Enabling Study | Alta Sciences
