Origin stories of the peptides shaping modern medicine.

Lizard saliva. Pig duodenum. A pancreatic tumor that finally gave up GHRH. The peptides we prescribe today were rarely designed top-down — they were dug out of unlikely places by stubborn researchers, and the twist in each story usually mattered more than the original hypothesis.

1. No. 011983–1987Boston, MA · Massachusetts General Hospital

   GLP-1 (Glucagon-Like Peptide-1)

   Incretin · GLP1R agonist family · Joel Habener, Svetlana Mojsov, Daniel Drucker
   The hunt

   While sequencing the proglucagon gene from anglerfish, Habener's lab noticed an extra glucagon-like sequence hidden in the precursor. Mojsov painstakingly synthesized fragments by hand to identify which one was bioactive — the now-famous 7-37 form. Drucker showed it triggered insulin secretion in a glucose-dependent way.

   The twist

   The bioactive fragment was not the obvious one. The full-length peptide did almost nothing; only the truncated 7-37 form bound the receptor. A trimming detail nobody predicted became a USD-100B drug class.

   The legacy

   Direct lineage to liraglutide, semaglutide, and tirzepatide — the backbone of modern obesity and diabetes care.

2. No. 021992Bronx VA Medical Center, New York

   Exenatide (from Exendin-4)

   GLP-1 receptor agonist · exendin scaffold · John Eng
   The hunt

   Endocrinologist John Eng was screening reptile venoms for hormones that affected the pancreas. The saliva of the Gila monster (Heloderma suspectum) — a venomous desert lizard that eats only a few times a year — contained a peptide that stimulated insulin secretion in a glucose-dependent way and lasted far longer than human GLP-1.

   The twist

   The VA wasn't interested in patenting it. Eng filed the patent himself in 1993. Amylin Pharmaceuticals later licensed it; it became Byetta in 2005 — the first GLP-1 drug on the market.

   The legacy

   Proved long-acting GLP-1 agonism was clinically viable, opening the door to every GLP-1 that followed.

3. No. 032012 (disclosed) · 2017 (approved)Bagsværd, Denmark · Novo Nordisk

   Semaglutide

   Lipidated GLP-1 analog · Lotte Bjerre Knudsen and team
   The hunt

   Building on liraglutide, the team replaced one amino acid with Aib to block DPP-4 cleavage and attached a longer C18 fatty-diacid linker for stronger albumin binding. The goal: a GLP-1 you could inject once a week instead of once a day.

   The twist

   The weight-loss effect was originally a 'side benefit.' STEP-1 (2021) showed ~15% body-weight reduction — comparable to early bariatric surgery — and the field's center of gravity shifted from diabetes to obesity overnight.

   The legacy

   Ozempic / Wegovy. The most commercially successful peptide in history.

4. No. 042016–2022Indianapolis · Eli Lilly

   Tirzepatide

   Dual GIP/GLP-1 receptor agonist · Lilly Diabetes Discovery team
   The hunt

   GIP had been considered a dead end — it didn't lower glucose well in diabetics on its own. Lilly's bet was that combining a modified GIP backbone with GLP-1 activity in a single molecule (a 'twincretin') would unlock weight loss neither could achieve alone.

   The twist

   GIP agonism alone causes weight gain. GIP + GLP-1 agonism causes more weight loss than GLP-1 alone. Why? Still being argued — possibly via central nausea/satiety circuits where GIP modulates GLP-1's tolerability.

   The legacy

   Mounjaro / Zepbound. SURMOUNT-1 hit ~22% weight loss — re-setting expectations again.

5. No. 051991Zagreb, Croatia · University of Zagreb

   BPC-157

   Body Protection Compound · gastric peptide fragment · Predrag Sikirić
   The hunt

   Sikirić's group was studying a protein in human gastric juice that seemed to protect the stomach lining from ulcers. They isolated a 15-amino-acid fragment they named BPC ('Body Protection Compound') and showed it accelerated healing of tendon, muscle, and gut tissue in rodent models.

   The twist

   Despite 30+ years of mostly preclinical data and enthusiastic adoption in sports medicine, BPC-157 has never completed a Phase 3 human trial. The receptor it acts on is still not definitively identified.

   The legacy

   One of the most-discussed 'research peptides' in regenerative medicine — and a case study in why preclinical promise is not the same as approval.

6. No. 061953 (synthesis)Cornell Medical College, New York

   Oxytocin

   Posterior pituitary nonapeptide · Vincent du Vigneaud
   The hunt

   Oxytocin's effects on labor were known since 1906, but nobody had isolated, sequenced, or synthesized it. Du Vigneaud purified it from pituitary extracts, determined the 9-amino-acid sequence with its disulfide bridge, and chemically synthesized it from scratch.

   The twist

   It was the first polypeptide hormone ever synthesized. Du Vigneaud won the 1955 Nobel Prize in Chemistry the year he published it.

   The legacy

   Foundational — proved that peptide hormones could be made by chemists, not just extracted from animals. Every synthetic peptide drug descends from this proof.

7. No. 071977 (Met-Enk derivatives) · 1998 (Ipamorelin)New Orleans · Tulane University, then Novo Nordisk

   GHRP-6 / Ipamorelin (Growth Hormone Secretagogues)

   Ghrelin receptor (GHSR) agonists · Cyril Bowers, then Hansen et al.
   The hunt

   Bowers noticed that synthetic enkephalin analogs released growth hormone from pituitary cells — through a receptor distinct from GHRH. He spent two decades evolving these into GHRP-6, GHRP-2, and hexarelin. Novo Nordisk later designed Ipamorelin to be a cleaner, more selective GH releaser without raising cortisol or prolactin.

   The twist

   The 'mystery receptor' Bowers had been chasing turned out to be the receptor for ghrelin — a hunger hormone discovered in 1999 by working backwards from the synthetic GHRPs. The drugs revealed the hormone, not the other way around.

   The legacy

   GHSR agonists remain a primary tool for stimulating endogenous GH pulsatility — preserving feedback in a way exogenous HGH cannot.

8. No. 081982Salk Institute, La Jolla, CA

   Sermorelin / Tesamorelin (GHRH Analogs)

   GHRH receptor agonists · Roger Guillemin, Wylie Vale
   The hunt

   Guillemin's group spent years searching for the hypothalamic factor that triggered pituitary GH release. The breakthrough came not from the hypothalamus but from a pancreatic tumor in a patient with acromegaly — the tumor was ectopically producing GHRH in such large quantities it could finally be purified.

   The twist

   The hypothalamic hormone was discovered via a pancreatic cancer. Guillemin had already won the Nobel Prize (1977) for other releasing hormones; GHRH was the last major one to fall.

   The legacy

   Sermorelin (1-29 fragment) and tesamorelin (stabilized analog) — used today for visceral fat reduction and physiologic GH restoration.

9. No. 091996 (gene) · 2003 (function)Hershey, PA · Penn State College of Medicine

   Kisspeptin

   KISS1R agonist · upstream of GnRH · Danny Welch (gene), then multiple labs (function)
   The hunt

   The KISS1 gene was first identified as a metastasis suppressor in melanoma — and named after Hershey's Kisses, made in the same town. Years later, three independent groups discovered that mutations in its receptor caused hypogonadotropic hypogonadism: kisspeptin was the master upstream switch for GnRH release.

   The twist

   A cancer-suppressor gene named after a chocolate turned out to be the trigger that starts puberty in every human.

   The legacy

   Kisspeptin-10 is now in trials for HPG-axis restoration — a more physiologic alternative to clomiphene/HCG for hypogonadism and fertility.

10. No. 101987Oxford, UK

    Pramlintide (from Amylin)

    Amylin receptor agonist · Garth Cooper, Per Westermark
    The hunt

    Pathologists had noticed amyloid deposits in the islets of type 2 diabetics for nearly a century but didn't know what they were. Cooper and Westermark identified the protein: a 37-amino-acid peptide co-secreted with insulin from beta cells. They named it amylin (later: islet amyloid polypeptide, IAPP).

    The twist

    Native amylin aggregates and is unusable as a drug. Substituting three prolines (the Pro-rich rodent sequence) gave pramlintide — soluble, stable, and the parent of cagrilintide, now paired with semaglutide for next-generation weight loss.

    The legacy

    Validated a second beta-cell hormone. Cagrilintide + semaglutide (CagriSema) is one of the most-watched late-stage obesity programs.