The current wave of interest in peptides can feel like a sudden trend, but peptide medicine has a century-long history, and today's GLP-1 drugs are the latest chapter in a much longer story.
Insulin: The First Peptide Drug
Insulin, isolated and first used therapeutically in 1921 by Frederick Banting, Charles Best, and colleagues, was arguably the first peptide drug, transforming type 1 diabetes from a near-certain death sentence into a manageable chronic condition. Early insulin was extracted from animal pancreases; it wasn't until 1978 that recombinant human insulin became possible, using genetically engineered bacteria to produce the human version of the peptide directly, a major milestone in biotechnology.
The Recombinant DNA Era
The 1970s and 80s brought a wave of peptide and protein drugs made possible by recombinant DNA technology: synthetic growth hormone, replacing a supply that had previously and tragically relied on hormone extracted from human cadavers, along with various interferons and other peptide-based therapies. This era established the manufacturing infrastructure and regulatory pathways that later peptide drugs would follow.
Discovering GLP-1
The hormone behind today's biggest peptide drugs, glucagon-like peptide-1, was identified in the 1980s as a gut hormone released after eating that stimulates insulin release. Researchers quickly recognized its potential for diabetes treatment, but the native hormone's half-life of only a couple of minutes made it useless as a drug on its own. The real breakthrough was chemical: finding ways to modify the molecule so it would resist rapid breakdown.
From Exenatide to Semaglutide
Exenatide, approved in 2005 and derived from a peptide found in Gila monster venom, was the first GLP-1 receptor agonist drug, dosed twice daily. Liraglutide followed with once-daily dosing. Semaglutide, approved in 2017 for diabetes and 2021 for weight management, extended that to once weekly through fatty-acid chain modifications that bind the molecule to albumin in the blood, dramatically slowing its clearance. Tirzepatide, approved in 2022, added a second mechanism, activating the GIP receptor alongside GLP-1, and newer candidates like retatrutide have added a third, glucagon receptor activity, continuing the same design trajectory of layering additional mechanisms onto the original gut-hormone discovery.
The Pattern Worth Noticing
Each major advance in this history came from the same combination: identifying a natural peptide signal, then using chemistry to solve its practical limitations, stability, half-life, selectivity, well enough to turn it into a reliable medicine, backed by large clinical trials before reaching patients. That pattern is exactly what separates a peptide with a century of therapeutic lineage behind it from one that simply shares a chemical category with insulin and GLP-1 but hasn't gone through the same process.
A Familiar Pattern Repeating
The recent GLP-1 boom, complete with shortages, compounding controversies, and a flood of new peptide interest online, echoes earlier moments in this history, including the transition from cadaver-derived to recombinant growth hormone, when demand outpaced regulated supply and unregulated alternatives moved in to fill the gap. Recognizing that pattern doesn't resolve today's specific questions about compounded GLP-1s or research-chemical peptides, but it's a useful reminder that this tension between demand, supply, and regulation isn't new to peptide medicine, it's arguably a recurring feature of it.