Therapeutic Use of Peptides: Clinical Guidelines
Primary Medical Applications
Peptides have established therapeutic roles primarily in cardiovascular diagnostics and metabolic disease management, with natriuretic peptides serving as validated biomarkers for heart failure diagnosis and GLP-1 receptor agonists approved for diabetes and weight management. 1
Cardiovascular Applications
Natriuretic peptides (BNP and NT-proBNP) are the most clinically validated peptide biomarkers, serving critical diagnostic and prognostic functions in acute cardiac care 2:
- For acute dyspnea diagnosis: BNP <100 pg/mL or NT-proBNP <300 pg/mL effectively rules out heart failure 2, 3
- Age-adjusted NT-proBNP thresholds for heart failure diagnosis: >450 pg/mL (<50 years), >900 pg/mL (50-75 years), >1800 pg/mL (>75 years) 2
- For chronic heart failure exclusion: BNP <35 pg/mL or NT-proBNP <125 pg/mL in ambulatory patients 3, 1
Critical limitation: Routine BNP/NT-proBNP testing is not warranted for making specific therapeutic decisions in acute or chronic heart failure due to significant intra- and inter-individual variations and mixed clinical trial results 2. The GUIDE-IT trial demonstrated that natriuretic peptide-guided therapy did not improve outcomes compared to standard clinical assessment 2.
Prognostic value is established: A >30% decrease in natriuretic peptides during heart failure treatment indicates good prognosis 2, and pre-discharge levels predict post-discharge outcomes more reliably than admission values 2.
Metabolic and Weight Management
GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists are FDA-approved for diabetes treatment and weight management 1. However, nutrition supplements containing peptides lack evidence for obesity management or weight loss, with most trials rated as low quality and high risk for bias 1.
Critical Care Applications
L-glutamine peptides (0.2-0.4 g/kg/day) in parenteral nutrition show benefits for critically ill patients with moderate strength of evidence 1. However, peptide-based formulas demonstrate no clinical advantage over whole protein formulas in this population 1.
Dermatologic Applications
Peptides show promise for photodamaged skin by increasing dermal thickness, promoting collagen synthesis, and enhancing fibroblast activity 4. Platelet-rich fibrin (containing natural peptides) improves periorbital wrinkles and hyperpigmentation 4.
For fibrotic skin conditions, relaxin peptides inhibit collagen biosynthesis and promote breakdown, though standardized protocols require further research 4.
Key Clinical Considerations
Adjustments for Special Populations
Obesity (BMI >35 kg/m²): Lower BNP cutoff to 55 pg/mL for heart failure exclusion 3
Renal impairment (eGFR <60): Use higher natriuretic peptide cutoffs due to reduced clearance 2, 3
Atrial fibrillation: Increase natriuretic peptide thresholds by 20-30% 2
Black patients: Consider lowering thresholds by 20-30% to avoid inappropriate exclusion 2
Safety Profile
Peptide therapeutics are generally well-tolerated with high selectivity and efficacy 5, 6. However, potential toxicities include intestinal wall disruption, cytotoxicity, and immunogenicity concerns 7. Regulatory assessment follows both small molecule (ICH M3) and biologic (ICH S6) guidance depending on peptide characteristics 8.
Delivery Challenges
Parenteral administration remains standard due to poor oral bioavailability, variable solubility, and limited stability 9. Nanobiotechnology approaches for oral, pulmonary, and transdermal delivery are emerging but not yet widely validated 9.
Clinical Algorithm for Natriuretic Peptide Use
- For acute dyspnea: Measure BNP or NT-proBNP with age-adjusted cutoffs 2
- If very low (<100 pg/mL BNP or <300 pg/mL NT-proBNP): Heart failure effectively ruled out 2, 3
- Adjust interpretation for obesity, renal function, and atrial fibrillation 2, 3
- Do not use for treatment titration decisions due to lack of validated benefit 2
- Use for risk stratification: Measure at admission and pre-discharge; >30% reduction indicates better prognosis 2