The short definition
The Talking Glossary of the National Human Genome Research Institute (NHGRI) defines a peptide as a short amino acid chain, usually 2 to 50 units long, held together by chemical links called peptide bonds. A longer chain, 51 amino acids or more, is a polypeptide, and the proteins your cells make are built from one or more polypeptides [1].
The National Cancer Institute dictionary puts it more broadly: a peptide is any molecule with two or more amino acids, and peptides with many amino acids are called polypeptides or proteins [2]. So the boundary is a convention rather than a law of nature.
Amino acids, the links in the chain
MedlinePlus describes amino acids as the molecules that combine to form proteins. When you digest protein from food, it is broken back down into amino acids, which the body then reuses to build its own proteins for growth, repair and many other jobs [3].
Nine amino acids are called essential because the body cannot make them and they must come from food: leucine, isoleucine, valine, lysine, methionine, phenylalanine, threonine, tryptophan and histidine. Others, such as alanine, glycine and proline, the body can make itself, and MedlinePlus lists some, including arginine and glutamine, as conditionally essential in times of illness and stress [3]. The order of amino acids in a chain is what gives each peptide its identity.
Peptides your body already makes
Many hormones are peptides. GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) carry the words in their names; both are released by the gut after a meal. Amylin is a peptide hormone made by the beta cells of the pancreas [8]. The labels of approved medicines also describe GLP-2 and growth hormone-releasing factor (GRF) as natural peptides that their products copy [9][10].
Natural peptide hormones are often short-lived. According to the Saxenda® label, the half-life of the body’s own GLP-1 is just 1.5 to 2 minutes, because enzymes called DPP-4 and neutral endopeptidase break it down [6]. Much of the work behind peptide medicines is making a hormone last long enough to be useful.
How long are peptide medicines?
The description section of each label gives the size of the molecule. Some give an amino acid count; others give only the molecular weight, measured in daltons (Da) or grams per mole.
| Ingredient (brand) | What it is based on | Size in the label |
|---|---|---|
| Teduglutide (Gattex®) | GLP-2 | 33 amino acids; 3,752 Da [9] |
| Pramlintide (Symlin®) | Amylin | 37 amino acids; 3,949.4. US presentations now listed as discontinued [8][13] |
| Liraglutide (Saxenda®) | GLP-1 (97% sequence match) | 3,751.2 Da [6] |
| Semaglutide (Ozempic®, Wegovy®) | GLP-1 (94% sequence match) | 4,113.58 g/mol [4] |
| Tirzepatide (Mounjaro®, Zepbound®) | GIP sequence | 4,813.53 Da [7] |
| Tesamorelin (Egrifta SV®) | Growth hormone-releasing factor | 44 amino acids plus a side chain; 5,135.9 Da. Above the FDA’s 40-amino-acid line [10][11] |
How a hormone becomes a medicine
The labels show the common tricks. Semaglutide has an amino acid changed at position 8 to resist DPP-4, and a fatty acid chain attached at position 26 so it binds to albumin in the blood [4]. Liraglutide carries a 16-carbon fatty acid (palmitic acid) at position 26 [6], and tirzepatide a 20-carbon fatty diacid [7]. Pramlintide differs from human amylin at three positions, where proline replaces the original amino acids [8].
Production varies too. The labels say the semaglutide backbone is made by yeast fermentation, liraglutide using recombinant DNA in yeast, teduglutide using modified E. coli bacteria, and tesamorelin and pramlintide synthetically [4][6][9][10][8].
This is an old field. A 2021 review in Nature Reviews Drug Discovery counted more than 80 peptide medicines on the market since insulin was introduced, for conditions from diabetes and osteoporosis to HIV infection and chronic pain [14]. It is a narrative overview by peptide chemists rather than a systematic count.
Peptide or protein: the regulatory line
Dictionaries can leave the boundary loose; a regulator cannot. The FDA describes peptides as polymers of 40 or fewer amino acids, and since 23 March 2020 longer chains that count as proteins have been regulated as biological products [11]. By that measure teduglutide, pramlintide and tirzepatide are peptides.
Tesamorelin shows what happens just above the line. Its label describes 44 amino acids [10], and the FDA’s own listing says its former new drug application was deemed a biologics licence on 23 March 2020 [12]. The article on approved peptide medicines covers this line, and insulin, in more detail.
Why most peptide medicines are injected
The body treats a peptide medicine much like other proteins: it cuts it up. The labels for semaglutide and tirzepatide say both are broken down by cleaving the peptide backbone, and the Gattex® label expects teduglutide to be degraded into small peptides and amino acids [4][7][9].
Swallowing a peptide therefore wastes most of it. Injected under the skin, semaglutide has an absolute bioavailability of 89%, according to the Wegovy® label; as a tablet it is about 1% to 2%, even with an added absorption enhancer called SNAC [5]. That is why nearly every peptide medicine in the table above is an injection, and why the semaglutide tablets come with strict instructions.
A chemical word, not an approval
Calling something a peptide says what it is made of. It says nothing about whether it has been tested or approved. Every medicine in the table was approved by the FDA with a label that sets out its use, dose and warnings, though approval does not guarantee a product is still sold: the Symlin® presentations are now listed as discontinued [13]. Egrifta SV®, for example, is approved only to reduce excess abdominal fat in adults with HIV and lipodystrophy [10].
Products sold as research peptides have no such label. The FDA has warned companies that sold unapproved peptide drugs falsely labelled “for research purposes” or “not for human consumption” directly to consumers with dosing instructions [15]. The article on their regulatory status explains more.
Ozempic®, Wegovy® and Saxenda® are registered trademarks of Novo Nordisk A/S. Mounjaro® and Zepbound® are registered trademarks of Eli Lilly and Company. Symlin® is a registered trademark of the AstraZeneca group of companies, Gattex® of Takeda Pharmaceuticals U.S.A., Inc., and Egrifta SV® of Theratechnologies Inc. PepLabo is not affiliated with or endorsed by any of these companies.
