PEPTOKING
EN

Glossary

Plain-language definitions of the words used in peptide research, regulation and medicine. Each entry lists its sources.

Accelerated approval

Accelerated approval is a US FDA pathway that lets a drug for a serious condition with an unmet need be approved sooner, based on a measure thought to predict real benefit.

That measure, called a surrogate endpoint, might be a lab test or a scan rather than a direct measure of how patients survive, feel or function. The company must still run studies to confirm the benefit, and the approval can be withdrawn or the label changed if they fail to do so. The FDA gave vosoritide (Voxzogo) accelerated approval in 2021 for children with achondroplasia, the most common form of dwarfism, based on their yearly growth rate, on condition of a later study of final adult height.

Peptides: VosoritideSee also: Primary endpoint, Marketing authorisation, Clinical trial phases

Adverse event

An adverse event is any unwanted medical occurrence in a person taking a drug, whether or not the drug caused it.

When there is a reasonable possibility that the drug caused it, it is called a suspected adverse reaction, and an adverse reaction is one the drug did cause. It counts as serious if, for example, it results in death, is life-threatening or leads to a hospital stay. In the SELECT trial, adverse events led 16.6% of people on semaglutide and 8.2% of those on placebo to stop treatment permanently.

Peptides: SemaglutideSee also: Placebo, Boxed warning, Observational study

Amino acid

An amino acid is the basic building block of proteins: 20 different amino acids are joined in long chains to make the proteins in the body.

The order of amino acids in a chain, called its sequence, determines a protein's 3-dimensional shape and its specific job. The body can make some amino acids itself, but others, the essential amino acids, must come from the diet. Peptide drugs can be close variants of natural sequences: semaglutide, which has a peptide backbone, shares 94% sequence homology (similarity) with the human hormone GLP-1.

Peptides: SemaglutideSee also: Peptide, GLP-1 (glucagon-like peptide-1)

Amylin

Amylin is a hormone released by beta cells in the pancreas together with insulin when food is eaten; it slows stomach emptying and helps curb appetite.

It also suppresses glucagon after meals, which reduces the release of glucose from the liver. People with type 1 or type 2 diabetes release less of both insulin and amylin in response to food. Pramlintide (Symlin), a synthetic analogue (modified copy) of human amylin with three amino acids replaced by proline, was approved in the US in 2005 for people with diabetes who use mealtime insulin. Cagrilintide, a long-acting amylin analogue, is under investigation for weight management.

Peptides: Pramlintide, CagrilintideSee also: Glucagon, Peptide

Bioavailability

Bioavailability is the extent to which the active ingredient of a medicine becomes available at its site of action, or in a body fluid thought to reflect that.

Peptides taken by mouth usually have low bioavailability, because they are broken down by enzymes and pass poorly through the lining of the gut. Semaglutide shows the gap: its absolute bioavailability is 89% when injected under the skin, but only about 1% to 2% from a tablet. The tablets contain an added ingredient, SNAC, that helps semaglutide be absorbed, mostly in the stomach.

Peptides: SemaglutideSee also: Pharmacokinetics, Subcutaneous injection

Biosimilar

A biosimilar is a biological medicine that is highly similar to an already approved biological medicine (the reference medicine), with no clinically meaningful differences.

Biological medicines come from living sources such as cells, so they cannot be copied exactly, and a biosimilar is not regarded as a generic. Insulin is regulated as a biologic in the US, which allows companies to make biosimilar versions of brand name insulins. Copies of some GLP-1 drugs have been approved as generics instead: in December 2024 the FDA approved the first generic referencing Victoza (liraglutide).

Peptides: Insulin (human), LiraglutideSee also: Peptide, Marketing authorisation

Boxed warning

A boxed warning is a warning about a serious risk, such as one that may lead to death or serious injury, that the FDA can require to be printed in a box on a prescription drug's label.

The box has a heading in capital letters that includes the word WARNING, briefly explains the risk and points to the fuller safety sections of the label. It is normally based on data from people, but serious harm seen in animals can be enough when human data are lacking. Wegovy (semaglutide) carries a boxed warning about a risk of thyroid tumours (C-cell tumours), because semaglutide causes them in rodents and it is unknown whether it does so in humans.

Peptides: SemaglutideSee also: Adverse event, Preclinical study, Marketing authorisation

Clinical trial phases

Clinical trial phases are the usual stages of testing a new medicine in people, from small early studies of safety (phase 1) to large trials that test whether it works (phase 3).

Phase 1 usually tests safety in a small group of healthy volunteers or patients, phase 2 involves up to several hundred people with the condition, and phase 3 usually involves 300 to 3,000. Because phase 3 trials are larger and longer, they are more likely to reveal rare or long-term side effects, and phase 4 studies continue after approval. Retatrutide, for example, was tested in a phase 2 trial in 338 adults and then in phase 3 trials such as TRIUMPH-1, in which 2,339 people were randomised.

Peptides: RetatrutideSee also: Preclinical study, Randomised controlled trial, Marketing authorisation

Compounding

Compounding is when a licensed pharmacist or doctor combines, mixes or alters a drug's ingredients to make a medication tailored to one patient's needs.

It can serve patients who cannot use an approved product, such as someone allergic to a dye or a child who cannot swallow a tablet. Compounded drugs are not FDA-approved, so the FDA does not check their safety, effectiveness or quality before they are sold. The FDA has received reports of adverse events linked to compounded semaglutide and tirzepatide, and says retatrutide and cagrilintide cannot be used in compounding under federal law.

Peptides: Semaglutide, Tirzepatide, Retatrutide, CagrilintideSee also: Research use only, Off-label use, Adverse event

Confidence interval

A confidence interval is the range of values around a study's result within which the true effect probably lies, showing how precise the result is.

A narrow interval means the effect is known precisely, while a very wide one means little is known about it. In SELECT, the hazard ratio for heart attack, stroke or cardiovascular death with semaglutide versus placebo was 0.80, with a 95% confidence interval of 0.72 to 0.90. In SURPASS-CVOT, the hazard ratio for tirzepatide versus dulaglutide was 0.92, but the interval ran from 0.83 to 1.01, so tirzepatide was shown to be not worse than dulaglutide but not shown to be better.

Peptides: Semaglutide, Tirzepatide, DulaglutideSee also: Hazard ratio, Non-inferiority trial, Meta-analysis

Double-blind

A double-blind trial is one in which neither the participants nor the researchers treating and assessing them know who is receiving which treatment.

Blinding limits the conscious and unconscious bias that knowing the treatment can introduce, for example in participants' care, their attitudes to the treatment and the assessment of results. It requires treatments that cannot be told apart, for example by appearance or taste. International trial guidance calls it the optimal approach, with single-blind or open-label designs used when it is not feasible. SELECT, which compared semaglutide with placebo in 17,604 people with cardiovascular disease and overweight or obesity, was double-blind.

Peptides: SemaglutideSee also: Placebo, Open-label, Randomised controlled trial

Estimand

An estimand is a precise description of the treatment effect a trial sets out to measure, including how events such as stopping treatment are handled.

Events after treatment starts, such as stopping the drug, adding or switching to another treatment, or death, can change what a result means, so the estimand states how each is dealt with. The ICH E9(R1) guideline, adopted in 2019, says the statistical analysis should be aligned to the estimand. In the STEP 1 trial of semaglutide, the primary estimand assessed the effect regardless of whether people stopped treatment or were given extra (rescue) treatment. The phase 3 TRIUMPH-1 trial of retatrutide reported knee pain results under two different estimands, and the figures differed.

Peptides: Semaglutide, RetatrutideSee also: Primary endpoint, Randomised controlled trial, Placebo

GIP (glucose-dependent insulinotropic polypeptide)

GIP (glucose-dependent insulinotropic polypeptide) is a hormone made in the gut that strongly stimulates the release of insulin.

It is one of the incretins, gut peptides that trigger insulin release from the pancreas after food is eaten. Its older name is gastric inhibitory polypeptide, but it is only a relatively poor inhibitor of stomach acid. The diabetes drug tirzepatide (Mounjaro) is based on the GIP sequence and activates both the GIP and GLP-1 receptors.

Peptides: TirzepatideSee also: GLP-1 (glucagon-like peptide-1), Receptor agonist

GLP-1 (glucagon-like peptide-1)

GLP-1 (glucagon-like peptide-1) is a hormone released by L cells in the gut after meals that boosts insulin release, curbs glucagon and slows stomach emptying.

Its effect on insulin depends on blood sugar, and it also reduces food intake and appears to act as a natural regulator of appetite. The body's own GLP-1 is broken down extremely quickly by an enzyme called dipeptidyl peptidase IV (DPP-4), even before it has left the gut. Semaglutide, a GLP-1 receptor agonist used for type 2 diabetes, is a modified copy of GLP-1 that resists DPP-4 and has a half-life of about a week.

Peptides: SemaglutideSee also: Receptor agonist, Glucagon, Half-life

Glucagon

Glucagon is a hormone made by alpha cells in the pancreas that raises blood sugar by making the liver break down its glycogen (stored sugar) and release glucose.

It is a chain of 29 amino acids made from proglucagon, the same precursor as the glucagon-like peptides made in the gut. Synthetic glucagon identical to the human hormone is an approved medicine for severe low blood sugar (hypoglycemia) in people with diabetes. Some experimental obesity drugs also act on its receptor: retatrutide is an agonist of the GIP, GLP-1 and glucagon receptors.

Peptides: RetatrutideSee also: GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), Receptor agonist

Half-life

Half-life is the time it takes for a substance, such as a drug, to lose half of its activity.

A long half-life means a drug lingers: semaglutide has an elimination half-life of about 1 week and stays in the circulation for about 5 weeks after the last dose. This comes mainly from semaglutide binding to albumin, a protein in the blood, which slows its removal by the kidneys and protects it from breakdown. The body's own GLP-1, by contrast, is broken down extremely rapidly by the enzyme dipeptidyl peptidase IV.

Peptides: SemaglutideSee also: Pharmacokinetics, GLP-1 (glucagon-like peptide-1)

Hazard ratio

A hazard ratio compares how likely an event is to happen at any given moment for people on one treatment versus another, where 1 means no difference.

A value below 1 means the event was less likely in the treatment group, and a value above 1 means it was more likely. It is the preferred way to summarise results when a trial measures the time until an event happens, such as death. In the SELECT trial, a non-fatal heart attack, non-fatal stroke or death from cardiovascular causes occurred in 6.5% of people on semaglutide and 8.0% on placebo, a hazard ratio of 0.80. It is a relative measure, so the absolute difference it stands for depends on how common the event is to begin with.

Peptides: SemaglutideSee also: Confidence interval, Primary endpoint, Meta-analysis

International Nonproprietary Name (INN)

An International Nonproprietary Name (INN) is the generic name of a medicine's active ingredient, selected through the WHO to be unique, recognised worldwide and public property.

INNs share word endings, called stems, that show the drug group: -tide marks peptides, and -glutide marks GLP-1 analogues such as liraglutide and semaglutide. The stem -dutide marks dual agonists of the GLP-1 and glucagon receptors, such as mazdutide and survodutide. To avoid confusion that could endanger patients, brand names (trademarks) should neither be derived from INNs nor contain their common stems.

Peptides: Liraglutide, Semaglutide, Mazdutide, SurvodutideSee also: Peptide, GLP-1 (glucagon-like peptide-1), Glucagon, Receptor agonist

Marketing authorisation

A marketing authorisation is the official licence a medicine needs before it can be marketed, sold or supplied, the term used in the EU and the UK.

In the EU, most innovative new medicines go through a single application to the European Medicines Agency, which gives a recommendation, and the European Commission then takes a legally binding decision valid across the EU and in Iceland, Liechtenstein and Norway. Other medicines are authorised country by country through national procedures. UK law says a medicine may not be sold or supplied except under a marketing authorisation or one of a few other listed registrations or authorisations. Wegovy (semaglutide) received an EU-wide marketing authorisation on 6 January 2022 after the agency judged that its benefits outweigh its risks.

Peptides: SemaglutideSee also: Accelerated approval, Clinical trial phases, Prescription-only medicine

Meta-analysis

A meta-analysis is the statistical combination of results from two or more separate studies to produce an overall estimate.

Combining studies can make an estimate more precise and answer questions that single studies cannot. It can also seriously mislead if the study designs, biases within studies, differences between them and selective reporting are not carefully considered. A 2021 meta-analysis of eight placebo-controlled trials of GLP-1 receptor agonists in people with type 2 diabetes found that, overall, they reduced major adverse cardiovascular events by 14%.

See also: Systematic review, Randomised controlled trial, Placebo, GLP-1 (glucagon-like peptide-1), Receptor agonist

Non-inferiority trial

A non-inferiority trial aims to show that a new treatment is not meaningfully worse than an existing effective treatment, rather than that it is better.

Before the trial, researchers set a margin, the largest shortfall they will accept, and the trial must statistically rule out a difference that large. They are usually chosen because a design aiming to show superiority, such as a comparison with placebo, cannot be used, and they rely on the comparison drug having worked as expected in the trial. In SURPASS-CVOT, tirzepatide was compared with dulaglutide, a drug already shown to reduce cardiovascular events, and was non-inferior for heart attack, stroke or cardiovascular death.

Peptides: Tirzepatide, DulaglutideSee also: Confidence interval, Hazard ratio, Placebo, Randomised controlled trial

Observational study

An observational study looks at people who receive a treatment as part of their routine medical care, without researchers assigning who gets it.

Common designs include cohort studies, which group people by the drugs they took, and case-control studies, which group people by whether they had a particular outcome. Without randomisation the results are more open to bias, so this evidence starts at a lower certainty than randomised trials, but it can supply data on rare harms that trials may not report. A 2024 study of patients seen by eye specialists at one academic centre found an association between semaglutide and an optic nerve condition called NAION, but its authors said that, as an observational study, it could not establish cause.

Peptides: SemaglutideSee also: Randomised controlled trial, Adverse event, Hazard ratio

Off-label use

Off-label use is prescribing or using an approved medicine outside the scope of its official label, such as for a different condition, in a different form or at a different dose.

In the US, once the FDA approves a drug, healthcare providers generally may prescribe it for an unapproved use when they judge it medically appropriate for their patient. This may happen when no approved treatment exists for a condition, or when approved treatments have not helped. The FDA has not determined that a drug is safe and effective for its unapproved uses.

See also: Prescription-only medicine, Marketing authorisation, Compounding

Open-label

An open-label trial is one in which both the participants and the researchers know which treatment each person is receiving.

Trials are run open-label when blinding is impractical or unethical, for example when the treatments are completely different, such as surgery and a drug, or come in different forms. Because everyone knows the treatment, results are more exposed to the conscious and unconscious bias that blinding is designed to limit, for example in how outcomes are assessed. SURMOUNT-5, a phase 3b trial that randomly assigned 751 adults with obesity to tirzepatide or semaglutide, was open-label.

Peptides: Tirzepatide, SemaglutideSee also: Double-blind, Placebo, Randomised controlled trial, Clinical trial phases

Peptide

A peptide is a short chain of amino acids linked by chemical bonds called peptide bonds; longer chains are called polypeptides, and proteins are made from them.

There is no precise, agreed line between a peptide and a protein, though one US government glossary describes peptides as typically 2 to 50 amino acids long. For US drug regulation, the FDA counts any amino acid chain longer than 40 as a protein, and proteins are regulated as biological products. Under that rule insulin, with 51 amino acids across its two chains, counts as a protein, while peptides are generally shorter, simpler chains.

Peptides: Insulin (human)See also: Amino acid, Biosimilar

Pharmacokinetics

Pharmacokinetics describes how a drug moves through the body over time: how it is absorbed, distributed, broken down (metabolised) and eliminated.

These steps are often summed up as ADME, short for absorption, distribution, metabolism and elimination. Drug labels report them: for semaglutide injection, blood levels peak 1 to 3 days after a dose, more than 99% of the drug is bound to albumin, a protein in the blood, and it is cleared mainly by breakdown of its peptide backbone. Its elimination half-life is about 1 week.

Peptides: SemaglutideSee also: Half-life, Bioavailability

Placebo

A placebo is an inactive treatment made to look as much like the real one as possible, used as a comparison in clinical trials.

Comparing with placebo separates the drug's own effect from everything else that can change during a trial, such as the natural course of the illness, the expectations of patients and doctors, and the effect of simply being in a trial. Placebo-controlled trials are almost always double-blind. In the STEP 1 weight-loss trial, people given placebo plus a lifestyle programme lost an average of 2.4% of their body weight over 68 weeks, compared with 14.9% for those given semaglutide.

Peptides: SemaglutideSee also: Double-blind, Randomised controlled trial, Open-label

Preclinical study

A preclinical study tests a potential medicine in the laboratory or in animals, before it is given to people, to answer basic questions about its safety.

Such research is not a substitute for studies of how a drug acts in the human body. In the US, a developer must give the FDA animal data, including evidence on serious harm (toxicity), before trials in people can begin. A 2025 systematic review of BPC-157 found 35 preclinical studies but only one clinical study, and while the preclinical safety studies showed no adverse effects, there were no clinical safety data in people.

Peptides: BPC-157See also: Clinical trial phases, Systematic review, Boxed warning

Prescription-only medicine

A prescription-only medicine is one that cannot legally be sold without a prescription from a doctor or another authorised health professional.

In the UK it is one of three legal categories, alongside pharmacy medicines and general sale list medicines, and it must be dispensed from a pharmacy or other specifically licensed premises. UK guidance applies this status when, for example, a medicine could endanger health if used without medical supervision, or is normally prescribed for parenteral use (given by a route that bypasses the gut, such as injection). In Canada, Health Canada says peptides are generally regulated as prescription drugs.

See also: Off-label use, Research use only, Marketing authorisation

Primary endpoint

The primary endpoint is the main outcome a trial is designed to measure, chosen in advance as the most relevant and convincing test of its main question.

There should generally be only one, and its exact definition should be fixed in the protocol, the written plan for the study, so that it is not redefined after the fact. Other outcomes are secondary endpoints, which support the main result or answer other questions. In the phase 2 trial of retatrutide, the primary endpoint was the change in body weight at 24 weeks, while the change at 48 weeks, when treatment ended, was a secondary endpoint.

Peptides: RetatrutideSee also: Estimand, Randomised controlled trial, Accelerated approval

Randomised controlled trial

A randomised controlled trial is a study in which chance decides which participants get the treatment being tested and which get a comparison, such as a placebo or another drug.

Randomisation tends to make the groups alike in factors that affect the outcome, known and unknown, and together with blinding it helps avoid bias in who gets which treatment. Studies without randomisation are more open to bias, so the GRADE approach used by Cochrane starts evidence from randomised trials at high certainty and evidence from non-randomised studies at low certainty. In the STEP 1 trial, 1,961 adults with overweight or obesity but no diabetes were randomly assigned to semaglutide or placebo, each alongside a lifestyle programme, for 68 weeks.

Peptides: SemaglutideSee also: Placebo, Double-blind, Observational study, Clinical trial phases

Receptor agonist

A receptor agonist is a substance that binds to a specific receptor and triggers a response, mimicking the action of a molecule the body makes itself.

Cell surface receptors are proteins that bind signalling molecules from outside a cell and turn them into signals inside it that change how the cell behaves. Tirzepatide, for example, is a GIP receptor and GLP-1 receptor agonist: it binds to and activates both receptors, the targets of the body's own GIP and GLP-1. An agonist's effect can be countered by an antagonist.

Peptides: TirzepatideSee also: GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide)

Research use only

Research use only is wording on products, including peptides sold online, saying they are meant for research and not for human consumption.

Regulators say the label does not make selling such products legal: Health Canada states it does not exempt them from regulatory requirements. The FDA has warned companies that sold unapproved drugs containing semaglutide, tirzepatide, retatrutide, survodutide or mazdutide, falsely labelled for research, directly to consumers with dosing instructions. Health Canada lists BPC-157, TB-500 and retatrutide among seized peptide products and says such unauthorised drugs have not been assessed for safety, efficacy and quality.

Peptides: Semaglutide, Tirzepatide, Retatrutide, Survodutide, Mazdutide, BPC-157, TB-500See also: Compounding, Prescription-only medicine

Subcutaneous injection

A subcutaneous injection delivers a liquid medicine under the skin through a hollow needle.

Injection avoids the gut, where peptides taken by mouth are broken down by enzymes and absorbed poorly, which leaves them with low bioavailability. Tirzepatide (Mounjaro), for example, is supplied as an injection for subcutaneous use. Its label reports a mean absolute bioavailability of 80% after subcutaneous injection.

Peptides: TirzepatideSee also: Bioavailability, Peptide

Systematic review

A systematic review gathers all the studies that meet pre-set criteria on a specific question and assesses them using explicit methods chosen to minimise bias.

Its methods are meant to be structured, transparent and reproducible, which is intended to give more reliable findings. A 2025 systematic review of BPC-157 in sports medicine identified 544 articles but included 36 studies, 35 of them preclinical and one a clinical study. The reviewers found no clinical safety data in humans.

Peptides: BPC-157See also: Meta-analysis, Preclinical study, Randomised controlled trial

WADA Prohibited List

The WADA Prohibited List is the World Anti-Doping Agency's list of substances and methods banned in sport, a mandatory standard that is updated every year.

A substance can be listed if it meets two of three criteria: it enhances or may enhance performance, it poses a health risk to athletes, or it violates the spirit of sport. Class S0 bans at all times any drug with no current government approval for human therapeutic use, naming BPC-157 as an example. Class S2 covers peptide hormones and growth factors, with examples including CJC-1295, ipamorelin, AOD-9604 and TB-500. The examples are not exhaustive, and each list is published three months before it takes effect on 1 January.

Peptides: BPC-157, CJC-1295, Ipamorelin, AOD-9604, TB-500