Peptide Therapeutics in Internal Medicine

Introduction to Peptide Therapeutics

• Peptides are short chains of amino acids with various physiological effects, and some peptide-based medications are FDA-approved with established safety and efficacy profiles, such as GLP-1 receptor agonists for diabetes and weight management 1
• The American College of Physicians recommends avoiding cash pay peptides due to limited regulatory oversight, inconsistent quality control, and potential safety concerns, including unknown drug interactions and adverse effects 1

FDA-Approved Peptides

• The American Gastroenterological Association recommends FDA-approved somatostatin analogs, such as octreotide, for neuroendocrine tumors 2
• The American Diabetes Association recommends FDA-approved GLP-1 receptor agonists, such as semaglutide and tirzepatide, for diabetes and weight management, with a known risk of delayed gastric emptying that could increase aspiration risk during procedures 1
• The American Heart Association recommends the use of peptides, such as natriuretic peptides, for diagnostic purposes in heart failure management, but not for routine therapeutic decisions in heart failure 3

Risks of Cash Pay Peptides

• The use of cash pay peptides may lead to unpredictable adverse effects, unknown long-term safety profiles, and potential for immunogenicity and antibody development, as well as interference with metabolism of other medications and delayed gastric emptying, which could increase aspiration risk during procedures 1
• Cash pay peptides may also worsen underlying conditions requiring proper medical management and delay initiation of evidence-based therapies, with potential risks including contamination with harmful substances and unknown actual peptide content and concentration 2

Diagnostic and Therapeutic Uses of Peptides

• The European Society of Cardiology recommends considering FDA-approved alternatives, such as somatostatin analogs, when peptide therapy might be indicated for neuroendocrine tumors 2

Clinical Recommendations

• Clinicians should avoid recommending cash pay peptides that lack FDA approval and rigorous clinical trial data, and educate patients about the risks of unregulated peptides and the availability of FDA-approved alternatives when appropriate 1
• Clinicians should report adverse events related to cash pay peptides to the FDA's MedWatch program and be aware of perioperative considerations if patients are using peptides, such as delayed gastric emptying requiring special anesthetic considerations 1
• The American College of Physicians recommends metformin plus lifestyle modifications as the first-line approach for diabetes management, with SGLT2 inhibitors and GLP-1 receptor agonists as second-line options, especially if heart failure, CKD, stroke risk, or weight loss is a goal 4, 5, 6
• SGLT2 inhibitors increase GLUT4 transporters and insulin receptors, reducing all-cause mortality, major adverse cardiovascular events, CKD progression, and heart failure hospitalizations, while GLP-1 receptor agonists improve insulin sensitivity and glucose uptake in muscles, reducing all-cause mortality, major adverse cardiovascular events, and stroke 4, 5, 6, 7
• The American College of Physicians strongly recommends avoiding DPP-4 inhibitors for reducing morbidity and mortality, based on high-certainty evidence 6
• Exercise and appropriate diet can increase GLUT4 expression, improve insulin sensitivity, and support weight management, as recommended by the American Diabetes Association 4, 6
• Dietary supplements like Sugar Guardian may contain undisclosed ingredients that could interfere with glucose metabolism, interact with prescription medications, or cause unpredictable effects on blood glucose levels, and relying on unproven supplements may delay initiation of evidence-based therapies, leading to worsening of diabetes and its complications 4, 6, 8, 9, 10