News & Insights Blog From Early Chemistry to the GLP-1 Era: How Peptides Became Cornerstones of Modern Medicine

From Early Chemistry to the GLP-1 Era: How Peptides Became Cornerstones of Modern Medicine

The Evolution of Peptides in Modern Medicine 

Over the past century, peptides have evolved from obscure chemical constructs into one of the most versatile and impactful classes of modern therapeutics. Today, peptide drugs are central to the treatment of diabetes, obesity, cancer, infectious diseases, cardiovascular disorders, and a growing number of rare and neurological conditions. The recent clinical and commercial success of GLP-1 receptor agonists has brought unprecedented attention to peptides, but this moment represents the culmination of more than a century of scientific progress rather than an abrupt revolution.1-3  

What Are Therapeutic Peptides and Why Are They Important? 

Peptides occupy a distinctive position between small molecules and large biologics. Typically composed of a few to several dozen amino acids, they combine high target specificity with the ability to modulate complex biological pathways, including protein–protein interactions that are often inaccessible to traditional drugs.2,3 These advantages are counterbalanced by intrinsic challenges, including structural stability, rapid enzymatic degradation, and limited oral bioavailability, which have historically constrained their clinical utility.2,3 

Early Foundations of Peptide Chemistry and Drug Development 

The conceptual foundations of peptide science were laid at the turn of the twentieth century by Emil Fischer, whose work defined the peptide bond and established that amino acids could be linked into ordered chains with predictable chemical properties.1 This insight transformed proteins and peptides from poorly understood biological materials into legitimate chemical entities, enabling rational synthesis and structural analysis. 

Insulin and the Birth of Peptide Therapeutics 

The first major clinical breakthrough followed with the discovery of insulin in the early 1920s. Its rapid translation into medical practice transformed diabetes from a fatal disease into a chronic, manageable condition and firmly established peptides as viable therapeutics.5–9 Insulin also foreshadowed themes that would recur throughout peptide drug development: exceptional potency, exquisite specificity, and the need for careful control of manufacturing, formulation, and dosing. Subsequent elucidation of insulin’s primary structure by Frederick Sanger confirmed that biological activity was encoded by precise amino acid sequences, reinforcing confidence in structure-based peptide design.5-7 

Breakthroughs That Enabled Scalable Peptide Drugs 

The mid-twentieth century saw the expansion of peptide therapeutics beyond insulin. Oxytocin and vasopressin became the first peptide hormones to be fully sequenced and chemically synthesized, demonstrating that synthetic peptides could faithfully reproduce endogenous biological activity.9 A decisive technological inflection point arrived with the invention of solid-phase peptide synthesis, which dramatically simplified peptide assembly and enabled the routine synthesis of longer, more complex sequences.4,10 This advance accelerated medicinal chemistry efforts and laid the groundwork for modern peptide manufacturing. 

Advances in Peptide Synthesis, Formulation, and Delivery 

By the late twentieth century, peptides had diversified into numerous clinical domains. Examples include enfuvirtide for HIV infection, ziconotide for severe chronic pain, somatostatin analogs for neuroendocrine tumors, and GLP-2 analogs for short bowel syndrome.3 In parallel, advances in chemical modification, cyclization, sustained-release formulations, and alternative delivery routes addressed many of the liabilities that once limited peptide drugs.2,3 

The current GLP-1 era represents a convergence of decades of biological insight and chemical innovation. GLP-1, a gut-derived incretin hormone, plays a central role in glucose homeostasis but is rapidly degraded in its native form. 11,17 Through targeted sequence substitutions and lipidation strategies, researchers engineered long-acting GLP-1 receptor agonists that resist degradation and allow once-weekly dosing. These agents have redefined standards of care for type 2 diabetes and obesity, while also demonstrating cardiovascular and renal benefits in large outcomes trials.11-13,16 

Dual and Multi-Incretin Peptides Beyond GLP-1 

Importantly, GLP-1 therapies are not the endpoint of peptide innovation. Dual and triple incretin agonists illustrate how peptides can be engineered to integrate multiple hormonal signals into a single molecule, further expanding therapeutic impact.11,12,14 These advances highlight peptides as a mature yet still rapidly evolving drug modality. 

Why Peptides Are Strategically Important for Drug Developers 

For drug developers and manufacturing partners, this historical arc carries practical implications. Modern peptide programs increasingly involve longer sequences, multiple chemical modifications, and sophisticated delivery systems, placing new demands on manufacturing, analytical capabilities, and regulatory strategy.2,3 The infrastructure built through a century of peptide science is now enabling the next generation of complex, high-impact therapies. 

The full white paper explores this trajectory in greater depth, tracing how foundational chemistry evolved into today’s peptide medicines and why the GLP-1 era is best understood within this broader historical context. 1-3 

Read the full white paper: History of Peptides in Medicine: From Early Chemistry to the GLP-1 Era 

References  

  1. V.V. Suresh Babu, One Hundred Years of Peptide Chemistry. Resonance, 16, 640 (2011). doi.org/10.1007/s12045-011-0071-7  
  1. B. Zheng, et al., Therapeutic Peptides: Recent Advances in Discovery, Synthesis, and Clinical Translation. Int. J. Mol. Sci., 26(11), 5131(2023). doi.org/10.3390/ijms26115131 
  1. L. Wang, et al., Therapeutic Peptides: Current Applications and Future Directions. Signal Transduct. Target Ther., 7, 48 (2022). doi.org/10.1038/s41392-022-00904-4  
  1. K. Fosgerau and T. Hoffmann, Peptide-Based Drug Discovery: Current Status and Recent Advances. Drug Discov. Today, 27, 1030 (2022). doi.org/10.1016/j.drudis.2014.10.003 
  1. I. Vecchio, et al., The Discovery of Insulin: An Important Milestone in the History of Medicine. Front. Endocrinol., (9) (343536 (2018).  doi.org/10.3389/fendo.2018.00613 
  1. FDA History Office. 100 Years of Insulin. U.S. Food and Drug Administration. U.S. Food and Drug Administration    
  1. J.B. Buse, et al., 100 Years On: The Impact of the Discovery of Insulin on Clinical Outcomes, BMJ Open Diabetes Res Care, 9(1) (2021). doi.org/10.1136/bmjdrc-2021-002373 
  1. F. Sanger, Nobel Lecture: The Structure of Insulin. NobelPrize.org, 1958.  
  1. Nobel Foundation, Vincent du Vigneaud – Facts. NobelPrize.org   
  1. R.B. Merrifield, Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide. J. Am. Chem. Soc., 85, 2149 (1963).  
  1. D.J. Drucker, The GLP-1 Journey: From Discovery Science to Therapeutic Impact. J. Clin. Invest., 134(2), e175634 (2024). doi.org/10.1172/JCI175634  
  1. A. Moiz, et al., The Expanding Role of GLP-1 Receptor Agonists: A Narrative Review of Current Evidence and Future Directions. eClinicalMedicine, 86, 103363 (2025).  doi.org/10.1016/j.eclinm.2025.103363 
  1. C. Sorli, et al., Efficacy and Safety of Once-Weekly Semaglutide Monotherapy Versus Placebo in Patients with Type 2 Diabetes (SUSTAIN 1): A Double-Blind, Randomised, Placebo-Controlled, Parallel-Group, Multinational, Multicentre Phase 3a Trial. Lancet Diabetes Endocrinol., 5(4), 251 (2017). doi.org/10.1016/S2213-8587(17)30013-X    
  1. S.T. Bull, et al., Tirzepatide: A Novel, First-in-Class, Dual GIP/GLP-1 Receptor Agonist. J. Diabetes Complicat., 36(12), 108332 (2022). doi.org/10.1016/j.jdiacomp.2022.108332  
  1. H. Yao, et al., Comparative Effectiveness of GLP-1 Receptor Agonists on Glycaemic Control, Body Weight, and Lipid Profile for Type 2 Diabetes: Systematic Review and Network Meta-Analysis. BMJ, 384, e076410 (2024). doi.org/10.1136/bmj-2023-076410  
  1. P.J. Rodriguez, et al., Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among Adults with Overweight or Obesity. JAMA Netw Open, 8(1), e2457349 (2025). doi.org/10.1001/jamanetworkopen.2024.57349  
  1. D.J. Drucker, et al., Discovery, Characterization, and Clinical Development of the Glucagon-Like Peptides, J. Clin. Invest., 127(12),4217 (2017). doi: 10.1172/JCI97233.