GLP-1
Glucagon-Like Peptide-1
GLP-1 (Glucagon-Like Peptide-1) is an endogenous incretin hormone and its synthetic analogs (e.g., semaglutide, liraglutide, tirzepatide) are used clinically for type 2 diabetes management and obesity treatment. As a research peptide, native GLP-1(7-36) amide and GLP-1(7-37) are studied for their insulinotropic, appetite-suppressing, and neuroprotective properties. Its primary applications include glucose homeostasis, weight reduction, and cardiovascular risk reduction.
Mechanism of Action
GLP-1 binds to the GLP-1 receptor (GLP-1R), a G-protein coupled receptor (Gs-linked), activating adenylyl cyclase and elevating intracellular cAMP, which potentiates glucose-dependent insulin secretion from pancreatic beta cells. Simultaneously, it suppresses glucagon release from alpha cells, slows gastric emptying, and acts on hypothalamic and brainstem GLP-1Rs to reduce appetite and caloric intake. Peripheral GLP-1R activation also confers cardioprotective effects via reduction of inflammation and improved endothelial function.
Evidence by Health Goal(18 goals)
Dosing Protocols
15-30 minutes before meals, subcutaneous injection into abdomen, thigh, or upper arm
Cycle: Continuous use is typical in clinical settings; research use often follows 4-8 week assessment periods
Native GLP-1 has an extremely short half-life (~2 minutes in vivo) due to DPP-4 degradation, making frequent dosing necessary. Pharmaceutical analogs (semaglutide, liraglutide) have extended half-lives and are preferred clinically. Research-grade native GLP-1 requires careful handling, cold storage (2-8°C), and reconstitution with bacteriostatic water. Dose titration upward is recommended to minimize GI side effects.
Safety & Side Effects
GLP-1 and its analogs have a well-established clinical safety profile with decades of human data supporting their use in diabetes and obesity; however, pharmaceutical-grade analogs (semaglutide, liraglutide) are prescription medications in most jurisdictions, and research-grade peptide use carries unverified purity risks. Individuals with a personal or family history of medullary thyroid carcinoma, MEN2 syndrome, or pancreatitis should avoid GLP-1 receptor agonists.
Possible Side Effects
- !Nausea, particularly during dose initiation or escalation
- !Vomiting, most common in first 2-4 weeks of use
- !Diarrhea or loose stools, often transient
- !Decreased appetite and early satiety
- !Injection site reactions including redness, bruising, or mild pain
- !Hypoglycemia, primarily when combined with insulin or sulfonylureas
- !Transient headache and fatigue during adjustment period
- !Rare: pancreatitis (risk elevated in individuals with prior pancreatic disease)
Interactions
- -Insulin and sulfonylureas: Additive blood glucose lowering significantly increases hypoglycemia risk
- -Oral medications: Delayed gastric emptying can reduce absorption rate and peak plasma levels of orally administered drugs
- -Warfarin: GLP-1 analog use has been associated with altered INR; monitor closely if co-administered
- -Metformin: Generally safe to combine, may have complementary glycemic effects, but monitor for GI symptom additive burden
- -Alcohol: May potentiate hypoglycemia risk, particularly in fasted states
Cost & Where to Buy
Research-grade native GLP-1(7-36) amide from peptide vendors typically costs $40-120/month depending on dose and vendor purity. Pharmaceutical analogs (semaglutide, liraglutide) are significantly more expensive ($800-1,400/month without insurance). Compounded semaglutide has become a lower-cost alternative (~$200-400/month) through specialty pharmacies.
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