The First Peptide Drug

Overview

The question "what was the first peptide drug?" has several defensible answers depending on how one defines both "peptide" and "drug." Historically, animal-derived insulin — introduced in 1922–1923 after the Toronto discovery by Banting, Best, Macleod, and Collip — is usually cited as the first peptide drug. It was also one of the first drugs of any kind to be produced from animal tissue on an industrial scale.

Other candidates predate insulin in limited forms. Posterior pituitary extracts containing oxytocin and vasopressin were used obstetrically and for diabetes insipidus beginning in the 1910s. Anterior pituitary extracts containing ACTH and other peptides were used beginning in the 1930s and 1940s. All of these extracts contained peptides, though none had been purified to single-molecule status.

Synthetic peptide drugs emerged after World War II. Synthetic oxytocin (Pitocin-type formulations) became available in the 1950s following du Vigneaud's synthesis. Desmopressin (1972) was the first synthetic peptide analog with improved receptor selectivity and pharmacokinetics. Recombinant human insulin (1982) was the first recombinant DNA drug.

Early Peptide Drugs

• Animal-derived insulin (1923): First peptide drug in widespread use.
• Pituitary extracts (1910s–1950s): Used for obstetrics, diabetes insipidus, adrenal insufficiency.
• Animal-derived ACTH (late 1940s): Used for rheumatoid arthritis and related diseases.
• Synthetic oxytocin (1950s): First fully synthetic peptide hormone used clinically.
• Synthetic vasopressin (1950s): Followed shortly after oxytocin.
• Desmopressin (1972): First selective peptide analog.
• Leuprolide acetate (1985): First GnRH analog widely approved.
• Humulin (1982): First recombinant DNA drug.

Timeline

• 1923: Eli Lilly begins industrial production of insulin.
• 1928: Kamm separates oxytocin and vasopressin activities.
• 1949: Cortisone and ACTH enter clinical use.
• 1953: Oxytocin synthesis published.
• 1972: Desmopressin introduced.
• 1982: Recombinant insulin approved.
• 1985: Leuprolide approved.
• 2000s–2020s: GLP-1 agonists (semaglutide, tirzepatide) dominate peptide-drug revenue.

Background

The transition from peptide extracts to purified and eventually synthetic or recombinant peptide drugs illustrates a broader pattern in pharmaceutical history. Early drugs were often crude preparations of animal or plant origin, with variable potency and significant impurities. As chemistry and pharmacology matured, these preparations were replaced by standardized pure substances, then by synthetic analogs, and finally by rationally designed molecules with improved properties.

Peptide drugs have also followed a distinct arc compared to small-molecule drugs. Because peptides are relatively large, polar molecules with short half-lives in circulation, early peptide drugs faced delivery and stability challenges that limited their use. Innovations including solid-phase synthesis, protective modifications (PEGylation, fatty-acid conjugation, stapling), and alternative delivery systems (subcutaneous injection, oral absorption enhancers, inhalation) have gradually overcome many of these limitations.

Modern Relevance

The modern peptide-drug industry includes more than 80 approved products with combined annual sales in the tens of billions of dollars. Major therapeutic areas include diabetes and obesity (GLP-1 receptor agonists), oncology (GnRH analogs, somatostatin analogs), osteoporosis (teriparatide), reproductive medicine, and HIV therapy (enfuvirtide).

Looking back, insulin remains the clearest single answer to "what was the first peptide drug?" — not only because of its priority but because no other peptide drug has come close to matching its impact on medicine. For broader context, see peptide-history and first-recombinant-insulin.

Related Compounds

• Insulin
• Oxytocin
• Desmopressin
• Leuprolide
• Semaglutide