FOUNDING ERA1921
Insulin discovered
Frederick Banting and Charles Best at the University of Toronto isolate insulin from canine pancreas. The first therapeutic peptide, and the one that makes 'peptide medicine' a field.
PEPGAINS/HISTORY
◆ TIMELINE · 1921 → 2026
THE HISTORY OF PEPTIDES.
From the discovery of insulin in a Toronto lab in 1921 to retatrutide's 28.7% weight-loss Phase 3 readout in April 2026. Every major milestone in peptide medicine on a single timeline.
◆ ERAS
FOUNDING ERA
1920s–1950s · Discovery of insulin and first synthetic peptides.
CLASSICAL ERA
1960s–1990s · Hormone characterization and early peptide pharma.
MODERN ERA
2000s–2020 · GLP-1 revolution and research-peptide mainstreaming.
CURRENT ERA
2020–2026 · Dual/triple agonists, regulatory reshuffling.
FOUNDING ERA1953
Oxytocin synthesized
Vincent du Vigneaud accomplishes the first total synthesis of a biologically active peptide hormone (oxytocin). Wins the Nobel Prize in Chemistry two years later — a foundational moment for peptide therapeutics.
FOUNDING ERA1955
Vasopressin synthesized
Du Vigneaud completes the synthesis of vasopressin, the second major peptide hormone made in a lab. Confirms that complex signaling peptides can be reliably produced outside biology.
CLASSICAL ERA1965
TRH identified
Thyrotropin-releasing hormone (TRH) is characterized — a small 3-residue peptide regulating thyroid function. The first example of a hypothalamic releasing factor, opening the door to GHRH research.
CLASSICAL ERA1977
Somatostatin sequenced
The 14-residue inhibitor of GH release is characterized. Enables the first physiological understanding of GH pulsatility and sets up the foundation for GHRH/GHRP research.
CLASSICAL ERA1982
GHRH characterized
Roger Guillemin's group identifies Growth Hormone Releasing Hormone. Sermorelin — its shortest active analog — becomes the ancestor of today's tesamorelin, CJC-1295, and sermorelin protocols.
CLASSICAL ERA1985
Recombinant human GH released
Genentech launches Protropin, the first rDNA-produced human GH. Transforms peptide manufacturing — suddenly you can produce large peptides without animal extraction.
CLASSICAL ERA1991
BPC-157 isolated
Sikiric and colleagues at the University of Zagreb isolate a 15-residue fragment from human gastric juice with remarkable tissue-protective effects in animal models. Becomes the most-discussed research peptide of the next 30 years.
CLASSICAL ERA1996
Ghrelin discovered
Kojima and colleagues characterize ghrelin — the stomach-secreted 'hunger hormone' that also potently releases GH. Ghrelin receptor agonists like Ipamorelin become the basis of modern GH-pulse protocols.
CLASSICAL ERA1999
GLP-1 therapy pioneered
Exendin-4 (later exenatide) is identified as a durable GLP-1 receptor agonist derived from Gila monster saliva. Opens the door to the entire GLP-1 class — the most commercially successful peptide drugs in history.
MODERN ERA2005
Exenatide (Byetta) FDA-approved
The first GLP-1 receptor agonist approved for type 2 diabetes. Twice-daily injection, modest weight loss side effect. The class everyone else in GLP-1 therapy is standing on.
MODERN ERA2010
Tesamorelin (Egrifta) approved
FDA approves tesamorelin for HIV-associated lipodystrophy — first and still-only FDA-approved GHRH analog for specific use. Decades-long safety record now underlies its 2026 off-label resurgence.
MODERN ERA2014
Semaglutide filed
Novo Nordisk files semaglutide with the FDA after pivotal trials. A once-weekly GLP-1 engineered with a fatty-acid modification extending half-life from minutes to a full week. Changes obesity medicine permanently.
MODERN ERA2017
Ozempic approved (semaglutide for T2D)
Semaglutide approved for type 2 diabetes as Ozempic. Initial pick-up is strong among diabetologists; off-label weight-loss use begins building.
MODERN ERA2019
Rybelsus — first oral peptide GLP-1
Novo Nordisk launches Rybelsus, oral semaglutide using a SNAC absorption enhancer. Only ~1% bioavailability but the first oral GLP-1 on the market. Sets up the small-molecule GLP-1 race that orforglipron will eventually win.
MODERN ERA2021
Wegovy approved — weight loss as indication
Semaglutide 2.4mg is approved specifically for chronic weight management (Wegovy). The STEP 1 trial shows 14.9% mean weight loss over 68 weeks. Cultural phenomenon ensues.
CURRENT ERA2022
Mounjaro approved — first GIP/GLP-1 dual agonist
Tirzepatide (Mounjaro) approved for type 2 diabetes. First dual-agonist peptide drug — GIP + GLP-1 receptor activation. Produces 22.5% weight loss in SURMOUNT-1, surpassing semaglutide head-to-head.
CURRENT ERA2023September
FDA reclassifies BPC-157 (and others)
FDA's Pharmacy Compounding Advisory Committee places BPC-157 on the Category 2 list — banned from 503A/B compounding. Similar restrictions follow for thymosin alpha-1, epithalon, and others. Research-chemical channel continues in legal gray zone.
CURRENT ERA2023November
SELECT trial — cardiovascular benefit of GLP-1s
Semaglutide reduces major cardiovascular events by 20% in non-diabetic patients with obesity. First trial to prove a weight-loss drug reduces MACE. Expands the case for GLP-1s beyond glycemia and weight alone.
CURRENT ERA2023
Retatrutide Phase 2 — 24% weight loss
Eli Lilly's triple agonist (GLP-1 + GIP + glucagon) produces 24.2% weight loss in Phase 2. First signal that triple-agonism dramatically outperforms dual. Sets expectations for the TRIUMPH program.
CURRENT ERA2024April
FLOW trial — semaglutide slows kidney disease
Semaglutide reduces major kidney disease events by 24% in patients with type 2 diabetes and CKD. Effect size comparable to SGLT2 inhibitors. Third major organ-system benefit established.
CURRENT ERA2025February
FDA removes semaglutide from shortage list
Compounding pharmacies lose legal authority to produce compounded semaglutide. Hundreds of thousands of patients on compounded protocols must transition to branded Ozempic/Wegovy or discontinue. Lawsuits follow.
CURRENT ERA2025
CagriSema Phase 3 — 22.7% weight loss
REDEFINE 1 shows cagrilintide + semaglutide combo produces 22.7% mean weight loss. First amylin-layered approach to surpass 20% in Phase 3. Novo Nordisk files for approval.
CURRENT ERA2026April
Retatrutide TRIUMPH — 28.7% weight loss
Phase 3 TRIUMPH data: 28.7% mean body-weight reduction at 48 weeks — highest ever recorded in a Phase 3 obesity trial. Also demonstrates substantial osteoarthritis pain relief and significant A1C reduction in diabetics. Lilly expected to file NDA in Q4.
CURRENT ERA2026Mid-year
Orforglipron expected — first oral non-peptide GLP-1
Eli Lilly's once-daily oral small-molecule GLP-1 agonist is under FDA review. Approval could reshape access — lower manufacturing cost, no injections, no absorption enhancers. Potential inflection point for scale.
◆ WHERE WE GO NEXT
100 YEARS IN.
THE BEST IS NEXT.
Orforglipron approval decision mid-2026. CagriSema NDA filing. Retatrutide cardiovascular outcomes trial reading out in 2027. We're updating this page as the milestones land.