The History of Peptides: From Secretin to Semaglutide

125 Years of Discovery

The story of peptide science spans more than a century — from the first identification of a hormone to the modern blockbuster drugs that are reshaping medicine. Understanding this history provides perspective on where we are today and where the field is heading. Each milestone built on the one before it, and the peptides we use today exist because of discoveries made generations ago.

The Birth of Endocrinology (1902-1920s)

In 1902, British physiologists William Bayliss and Ernest Starling discovered secretin — a substance produced in the small intestine that stimulated the pancreas to secrete digestive juices. This was the first hormone ever identified, and Starling coined the word "hormone" (from the Greek hormon, meaning "to set in motion") to describe it. Secretin is a 27-amino-acid peptide, though its peptide nature was not fully understood at the time.

In 1921, Frederick Banting and Charles Best at the University of Toronto isolated insulin from pancreatic extracts and used it to treat diabetic patients. This was one of the most transformative medical breakthroughs of the 20th century. Insulin is a 51-amino-acid peptide hormone, and its discovery inaugurated the era of peptide therapeutics — even before scientists fully understood peptide chemistry. Banting received the Nobel Prize in 1923.

In 1928, Vincent du Vigneaud began the work that would eventually lead to the chemical characterization and synthesis of oxytocin and vasopressin — two 9-amino-acid peptide hormones produced by the hypothalamus. His synthesis of oxytocin in 1953 earned him the Nobel Prize in Chemistry in 1955 and proved that peptides could be manufactured in the laboratory.

The Structural Era (1950s-1960s)

In 1953, Frederick Sanger determined the complete amino acid sequence of insulin — the first protein ever fully sequenced. This landmark achievement, which earned Sanger his first Nobel Prize in 1958, established the tools and methods for understanding peptide structure at the molecular level.

In 1963, Robert Bruce Merrifield developed solid-phase peptide synthesis (SPPS), a technique that revolutionized peptide chemistry. Before Merrifield, synthesizing peptides was an excruciating, multi-step process that took months or years. SPPS attached the growing peptide chain to an insoluble solid support, allowing automated, stepwise addition of amino acids. This made it possible to synthesize custom peptides in days rather than months. Merrifield received the Nobel Prize in Chemistry in 1984. SPPS remains the foundation of peptide manufacturing today.

The Growth Hormone Revolution (1970s-1990s)

In 1971, Roger Guillemin and Andrew Schally independently characterized growth hormone-releasing hormone (GHRH) and other hypothalamic peptides that control pituitary function. Their work revealed the peptide signaling system that regulates growth hormone release — the same system targeted by modern GH secretagogues. Both received the Nobel Prize in Physiology or Medicine in 1977.

In 1981, the first synthetic growth hormone secretagogue — GHRP-6 — was developed by Cyril Bowers. This small peptide could stimulate growth hormone release from the pituitary, demonstrating that the GH axis could be manipulated with synthetic peptides. GHRP-6 launched an entire field of research into peptide-based GH stimulation.

In 1985, recombinant DNA technology enabled the production of biosynthetic human growth hormone (Protropin, then Humatrope), replacing the previous supply of GH extracted from cadaver pituitary glands — a practice that had been linked to transmission of Creutzfeldt-Jakob disease. This was one of the first biotechnology-produced peptide drugs.

In 1992, sermorelin (a 29-amino-acid GHRH analog) received FDA approval for the diagnosis and treatment of growth hormone deficiency in children. Though its approved use was later narrowed, sermorelin became one of the most widely used peptides in the compounding pharmacy space for age-related growth hormone decline.

The GLP-1 Era (1990s-2010s)

In 1987, researchers discovered that GLP-1 — a peptide produced in the gut — potently stimulated insulin secretion. This finding, primarily from the laboratories of Jens Juul Holst in Denmark and Joel Habener in the US, laid the foundation for the GLP-1 drug revolution. But natural GLP-1's 2-minute half-life made it impractical as a drug.

In 1992, John Eng, a researcher at the VA Medical Center in New York, isolated exendin-4 from the saliva of the Gila monster lizard. This peptide activated the GLP-1 receptor but resisted the DPP-4 enzyme that destroyed natural GLP-1. It became the basis for the first GLP-1 drug.

In 2005, exenatide (Byetta) — a synthetic version of exendin-4 — became the first GLP-1 receptor agonist approved by the FDA for Type 2 diabetes. It required twice-daily injection, which limited its appeal, but it proved the concept.

In 2010, liraglutide (Victoza) was approved for diabetes, using a fatty acid modification to extend the half-life to once-daily dosing. In 2014, a higher dose was approved as Saxenda for weight management — the first GLP-1 drug approved specifically for obesity.

In 2017, semaglutide (Ozempic) received FDA approval for Type 2 diabetes. Its once-weekly dosing, achieved through further molecular engineering, was a game-changer for patient convenience. In 2021, a higher dose was approved as Wegovy for weight management, and in 2019, an oral formulation (Rybelsus) became the first oral GLP-1 drug — a landmark achievement in peptide delivery technology.

In 2022, tirzepatide (Mounjaro) was approved for diabetes. As a dual GLP-1/GIP receptor agonist, it represented the next evolution in gut hormone therapeutics. In 2023, it was approved as Zepbound for weight management, with clinical trial data showing up to 22.5% body weight reduction.

The Modern Peptide Landscape (2020s-Present)

The convergence of several developments has brought peptides into the mainstream conversation:

• GLP-1 drugs became a cultural phenomenon. Semaglutide and tirzepatide generated tens of billions in annual revenue and became some of the most prescribed drugs in history. Their success validated peptide therapeutics as a major pharmaceutical category.
• Compounding access expanded. Drug shortages for GLP-1 medications, combined with growing demand for other peptides, expanded the role of compounding pharmacies in peptide access.
• Telehealth lowered barriers. The post-pandemic telehealth infrastructure made peptide prescriptions more accessible to patients who previously could not find knowledgeable local providers.
• BPC-157 and other research peptides gained attention. Peptides with primarily animal-study evidence attracted a large following in health optimization communities, driving demand through both compounding and gray-market channels.
• Regulatory battles intensified. The FDA's actions regarding compounded semaglutide, the evolving 503B framework, and congressional attention to peptide access created an active and uncertain regulatory environment.

What Comes Next

The peptide field is accelerating. Active areas of research include oral peptide delivery platforms that could eliminate the need for injection, multi-receptor agonists targeting three or more pathways simultaneously, peptide-drug conjugates for targeted cancer therapy, AI-driven peptide design that can predict optimal sequences computationally, and long-acting formulations that could extend dosing intervals to monthly or even less frequent administration.

The 125-year arc from secretin to semaglutide is a story of incremental scientific progress punctuated by breakthrough moments. Each generation of peptide scientists built on the work of those before them, and the tools available today — automated synthesis, structural biology, computational design, advanced delivery systems — are more powerful than anything previous generations could have imagined.

This article completes the Peptides Decoded curriculum. The goal of this series has been to build your understanding from zero to a level where you can evaluate peptide claims, read research, assess quality, and make informed decisions. The science will continue to evolve, and so will this resource. Thank you for learning with us.