Therapeutic Peptides
Introduction
Section titled “Introduction”Peptide therapeutics represent a rapidly growing class of drugs. They offer high specificity and potency with fewer side effects compared to small molecules. As of 2026, over 80 peptide drugs are FDA-approved, with many more in development.
Major FDA-Approved Peptide Drugs
Section titled “Major FDA-Approved Peptide Drugs”Metabolic Disorders
Section titled “Metabolic Disorders”| Drug | Target | Indication | Route |
|---|---|---|---|
| Insulin (various) | Insulin receptor | Diabetes | SC, IV |
| Semaglutide (Ozempic) | GLP-1 receptor | Type 2 diabetes | SC, Oral |
| Liraglutide (Victoza) | GLP-1 receptor | Type 2 diabetes | SC |
| Exenatide (Byetta) | GLP-1 receptor | Type 2 diabetes | SC |
Hormonal Disorders
Section titled “Hormonal Disorders”| Drug | Target | Indication | Route |
|---|---|---|---|
| Oxytocin (Pitocin) | Oxytocin receptor | Labor induction | IV, SC |
| Octreotide (Sandostatin) | SST receptors | Acromegaly | SC, IM |
| Leuprolide (Lupron) | GnRH receptor | Prostate cancer | SC, IM |
| Desmopressin (DDAVP) | V2 receptor | Bedwetting | IN, oral |
Routes of Administration
Section titled “Routes of Administration”- Intravenous (IV): Immediate effect, 100% bioavailability
- Subcutaneous (SC): Most common for peptide drugs
- Intramuscular (IM): Slower absorption than SC
- Intranasal (IN): Nasal delivery for CNS-targeted peptides
- Oral: Limited by GI degradation (semaglutide uses SNAC absorption enhancer)
- Intrathecal (IT): Direct CNS delivery
Half-Life Challenges
Section titled “Half-Life Challenges”Peptide drugs typically have short half-lives due to enzymatic degradation by proteases, renal clearance, and receptor-mediated clearance. Strategies to extend half-life include PEGylation (adding polyethylene glycol), albumin binding (e.g., semaglutide uses fatty acid conjugation), D-amino acid substitution to resist protease degradation, cyclization for increased stability, and depot formulations for slow release from injection sites.
Advantages and Limitations
Section titled “Advantages and Limitations”Advantages
Section titled “Advantages”- High specificity for target receptors
- High potency at low doses
- Low toxicity, few off-target effects
- Biodegradable to amino acids
- Predictable metabolism
Limitations
Section titled “Limitations”- Short half-life, frequent dosing
- Poor oral bioavailability
- Potential immunogenicity
- Complex manufacturing
- Susceptible to aggregation