A Century of Peptide Drugs: How 80+ Medicines Went from Insulin to Semaglutide
A Nature Reviews Drug Discovery perspective traces nearly a century of peptide drug development — from insulin's 1920s debut to 80+ approved drugs — and maps emerging strategies like venomics and display libraries that will shape the field's future.
Quick Facts
What This Study Found
Over 80 peptide drugs have reached the market since insulin's introduction, covering a remarkably diverse range of therapeutic areas. The review identifies several key waves of peptide drug development:
1) Early hormone-based drugs: insulin, oxytocin, vasopressin, ACTH
2) Medicinal chemistry era: rational design and chemical modifications to improve stability and selectivity
3) Nature-derived peptides: venom-derived drugs (ziconotide from cone snails, exenatide from Gila monster), natural product-inspired designs
4) Molecular biology advances: recombinant production, phage display, mRNA display
5) Emerging strategies: integrated venomics (systematic venom mining), peptide-display libraries, AI-guided design
The authors emphasize that lessons from earlier approaches remain highly relevant, and that peptide drugs occupy a unique pharmaceutical 'sweet spot' between small molecules and biologics.
Key Numbers
How They Did This
This is a Perspective article in Nature Reviews Drug Discovery — a high-impact review format that combines comprehensive literature analysis with expert opinion and forward-looking strategic assessment. The authors, who are leading peptide scientists, surveyed the entire history of peptide drug development, analyzed current trends and pipelines, and identified emerging opportunities and challenges.
Why This Research Matters
Peptide drugs represent one of the fastest-growing segments of the pharmaceutical industry, with blockbusters like semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) generating tens of billions in revenue. This authoritative review explains how we got here and where the field is headed. For anyone interested in peptide science — researchers, investors, patients, or clinicians — this is the definitive big-picture overview of the field's trajectory.
The Bigger Picture
This review captures a field at a transformative moment. When it was published in 2021, GLP-1 drugs were already growing rapidly, but the explosion in weight loss prescriptions was just beginning. The technologies described — venomics, display libraries, AI-guided design — are now producing the next generation of peptide therapeutics. The fundamental insight that peptides occupy a unique space between small molecules (easy to make, limited targets) and biologics (powerful but expensive) explains why peptide drugs continue to find new applications across virtually every therapeutic area.
What This Study Doesn't Tell Us
As a Perspective rather than a systematic review, the coverage reflects the authors' expertise and interests. The review was published in 2021, so it does not cover the most recent developments including the explosive growth of GLP-1 drugs for obesity, tirzepatide's approval, or advances in AI-guided peptide design. The pharmaceutical pipeline information is frozen at the time of writing. The review focuses primarily on approved drugs and advanced clinical candidates, with less coverage of very early-stage research.
Questions This Raises
- ?How will AI and machine learning accelerate peptide drug discovery beyond what venomics and display libraries can achieve?
- ?Will oral peptide delivery breakthroughs (like semaglutide's SNAC technology) be broadly applicable to other peptide drugs?
- ?Can peptide drugs capture market share from both small molecules and antibody biologics, or will they remain a niche category?
Trust & Context
- Key Stat:
- 80+ peptide drugs approved From insulin in the 1920s to modern GLP-1 blockbusters, peptide drugs have grown into a major pharmaceutical category spanning diabetes, cancer, pain, HIV, and beyond
- Evidence Grade:
- This is an expert Perspective article in one of the highest-impact drug discovery journals. It synthesizes decades of published research and provides authoritative analysis of field trends. While not primary research, it represents the most comprehensive and prestigious overview of peptide drug discovery available.
- Study Age:
- Published in 2021 in Nature Reviews Drug Discovery, this review captures the field just before the explosion of GLP-1 drugs for obesity. Many of the emerging strategies discussed (venomics, display libraries, AI) have advanced significantly since publication, making some content already partially historical.
- Original Title:
- Trends in peptide drug discovery.
- Published In:
- Nature reviews. Drug discovery, 20(4), 309-325 (2021)
- Authors:
- Muttenthaler, Markus(2), King, Glenn F(2), Adams, David J(3), Alewood, Paul F
- Database ID:
- RPEP-05633
Evidence Hierarchy
Frequently Asked Questions
Why are peptide drugs considered a unique category between small molecules and biologics?
Peptide drugs (typically 2-50 amino acids) combine advantages of both categories: they're more specific and potent than most small molecule drugs (which are simpler chemicals), yet smaller, cheaper, and easier to manufacture than large biologic drugs like antibodies. This 'sweet spot' allows peptides to target receptors and proteins that small molecules can't reach, while avoiding the manufacturing complexity of full-size biologics.
What is venomics and how is it used to discover peptide drugs?
Venomics is the systematic study of all peptides in animal venoms — from snakes, spiders, cone snails, scorpions, and other venomous creatures. These venoms have been refined by millions of years of evolution to contain potent, highly specific peptides. By analyzing venom libraries, researchers can find peptides that target specific human receptors and channels. Several approved drugs came from venoms, including the pain drug ziconotide (from cone snails) and the diabetes drug exenatide (from Gila monster saliva).
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Cite This Study
https://rethinkpeptides.com/research/RPEP-05633APA
Muttenthaler, Markus; King, Glenn F; Adams, David J; Alewood, Paul F. (2021). Trends in peptide drug discovery.. Nature reviews. Drug discovery, 20(4), 309-325. https://doi.org/10.1038/s41573-020-00135-8
MLA
Muttenthaler, Markus, et al. "Trends in peptide drug discovery.." Nature reviews. Drug discovery, 2021. https://doi.org/10.1038/s41573-020-00135-8
RethinkPeptides
RethinkPeptides Research Database. "Trends in peptide drug discovery." RPEP-05633. Retrieved from https://rethinkpeptides.com/research/muttenthaler-2021-trends-in-peptide-drug
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.