What are peptides and their therapeutic effects in adults?

Understanding Peptides and Their Therapeutic Applications

What Are Peptides?

Peptides are short chains of amino acids (typically 2-50 amino acids) linked together by peptide bonds, with a molecular weight less than 10 kDa 1, 2. They differ from proteins primarily by size—peptides generally contain fewer than 50 amino acids, while proteins contain more than 50 amino acids and often have multiple peptide subunits 1.

Therapeutic Applications of Peptides

FDA-Approved Peptide Medications

Peptides represent a well-established class of therapeutic agents, with over 60-80 peptide-based drugs currently approved by the FDA for various medical conditions 1, 2. The first peptide drug, insulin, was introduced commercially and paved the way for modern peptide therapeutics 1.

Current FDA-approved peptide applications include:

• Diabetes management: GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists are effective for weight management and diabetes treatment 3
• Cardiovascular disease: Natriuretic peptides (BNP, NT-proBNP) serve as valuable diagnostic markers for heart failure and cardiovascular risk assessment 3, 4
• Neuroendocrine tumors: Peptide receptor radionuclide therapy (PRRNT) using radiolabeled somatostatin analogues (90Y-DOTATOC, 177Lu-DOTATATE) achieves partial or complete responses in up to 30% of patients with somatostatin receptor-expressing tumors 5
• Multiple inflammatory diseases: Corticotropin was the first approved peptide in 1952 2
• Urological disorders and other chronic conditions 1

Diagnostic Applications

Natriuretic peptides have become essential diagnostic tools in cardiovascular medicine 5, 4:

• BNP levels <100 pg/mL make heart failure highly unlikely 4
• BNP >400 pg/mL has high positive predictive value for congestive heart failure 4
• BNP levels parallel NYHA functional class and provide objective evidence of heart failure severity 4
• Serial BNP measurements can track treatment response, though using BNP to guide medication titration has not proven superior to achieving target doses of evidence-based therapies 4

Critical Care Applications

L-glutamine peptides (0.2-0.4 g/kg/day) in parenteral nutrition for critically ill patients have shown benefits with moderate strength of evidence 3. However, peptide-based formulas show no clinical advantage over whole protein formulas in critically ill patients 3.

Advantages of Peptide Therapeutics

Peptides offer several key advantages as therapeutic agents 6, 7:

• High specificity: Peptides naturally mimic binding interfaces between proteins, allowing precise targeting of protein-protein interactions 7
• Increased selectivity compared to small molecules 6
• Smaller size compared to antibodies, allowing better tissue penetration 6
• Low toxicity and good biocompatibility 1, 7
• Natural production by the body, making them inherently biocompatible 1

Challenges and Solutions in Peptide Drug Development

Pharmacokinetic Limitations

Peptides face several pharmacologic barriers that have historically limited their clinical translation 7:

• Rapid clearance from circulation
• Proteolytic degradation
• Poor oral bioavailability
• Limited tissue penetration

Modern Engineering Solutions

Recent technological advances have transformed peptides into viable drug candidates through multiple strategies 6, 8:

• Chemical modifications: Cyclization, substitution with D-amino acids, N-methylation, and side-chain halogenation enhance stability 8
• Peptide-conjugates: These modifications lower clearance rates and increase drug exposure, making peptides suitable for chronic disease treatment 6
• Unnatural amino acids and mainchain modifications improve peptide stability and therapeutic potential 6
• Nanoparticle delivery systems: Self-assembled vehicles protect therapeutic peptides and deliver them to desired tissues 7

Important Clinical Caveats

Weight Loss and Nutrition Supplements

There is no clear evidence that nutrition supplements, including peptides, are effective for obesity management or weight loss outside of FDA-approved medications 3. Most trials evaluating nutrition supplements for weight loss are of low quality and at high risk for bias, with strength of evidence rated as low 3.

BNP Monitoring Limitations

When using natriuretic peptides for heart failure management, several critical limitations exist 4:

• Many patients on optimal medication doses continue to show markedly elevated BNP levels despite clinical improvement
• Some patients with advanced heart failure paradoxically demonstrate BNP levels within normal range
• BNP should not be used in isolation to confirm or exclude heart failure
• Obesity (BMI >30 kg/m²) significantly lowers BNP levels, potentially causing false negatives 4
• Advanced age (>75 years) and female sex are associated with higher baseline BNP values 4

Specialized Applications

For neuroendocrine tumors, PRRNT is indicated for patients with positive somatostatin receptor-2 expression, with ideal candidates being those with well-differentiated and moderately differentiated neuroendocrine carcinomas (NET grade 1 or 2) 5. The treatment can deliver tumoricidal absorbed doses exceeding 200 Gy to receptor-expressing tumors 5.