How a Peptide Becomes an Approved Medicine

Approval is the last step in a long sequence of questions, each answered by a different kind of study. Following one peptide medicine through that sequence shows what the word approved actually covers, and what it does not.

Before anyone receives it

Every medicine starts in the laboratory. Before a company may give a new compound to people in the United States, it has to submit an Investigational New Drug application, known as an IND, to the FDA. According to the FDA, the application has to include animal study and toxicity data, information on how the compound is manufactured, the plans for the clinical studies, any data from earlier human research, and information about the investigators. The FDA then has 30 days to review it. It can let the studies go ahead, or place them on clinical hold if it finds safety concerns or other problems.

Tirzepatide is a good worked example because its early work was published in one paper. Under the code LY3298176, it was tested in cell lines carrying the GIP and GLP-1 receptors, and in mice, where it lowered body weight and food intake more than a GLP-1 receptor agonist did. Only then did the first human studies begin.

The three phases of human trials

Phase 1: is it tolerable, and how does the body handle it?

Phase 1 studies usually involve 20 to 100 healthy volunteers or people with the condition and last several months. The FDA gives their purpose as safety and the dose range. For tirzepatide, 142 people received at least one dose of the compound, the comparator or placebo across single-dose and multiple-dose studies in healthy volunteers and a four-week study in people with type 2 diabetes. The results showed blood levels that supported a weekly schedule, and gastrointestinal side effects that increased with dose.

Phase 2: does it seem to work, and at what dose?

Phase 2 trials involve up to several hundred people with the condition and run from several months to two years. Their job is to show early evidence of efficacy and to map side effects, which usually means choosing the doses worth taking forward. The retatrutide phase 2 trial is a typical example: 338 adults, 48 weeks, several dose levels and different starting doses.

Phase 3: does it work, in enough people, safely enough?

Phase 3 trials involve 300 to 3,000 people or more and run for one to four years. They are the trials regulators rely on. The FDA says that, in general, two well-designed clinical trials are needed for approval, although one may be enough for a rare disease. Tirzepatide's SURPASS-2 trial enrolled 1,879 people and SURMOUNT-1 enrolled 2,539. Trials that measure hard outcomes such as heart attacks need far more: SURPASS-CVOT randomised 13,299.

Multiplying those figures gives a sense of the odds: of every 100 compounds that enter phase 1, roughly 70 reach phase 2, about 23 reach phase 3, and only around six clear phase 3. That is why an interesting result in animals, or in a small early study, says little about whether a compound will ever become a medicine.

How to read a trial

A few design features decide how much weight a trial can carry.

A comparison makes this concrete. SURMOUNT-1 was randomised, placebo-controlled, double-blind and registered, with 2,539 participants over 72 weeks. The small human reports on BPC-157 described elsewhere on this blog had no control group and no blinding, and involved 12 people or fewer. Both are published research, but they can support very different conclusions.

What a regulator decides

In the words of the FDA, approval means that its Center for Drug Evaluation and Research has reviewed the data on a drug's effects and determined that it provides benefits that outweigh its known and potential risks for the intended population. The decision comes with approved labelling, which sets out the uses, warnings and side effects, and sometimes with additional risk management requirements.

In Indonesia, BPOM gives marketing authorisation, known as izin edar. When it approved tirzepatide in 2026, BPOM said the evaluation covered safety, efficacy and quality, and followed international standards for good laboratory practice, good clinical practice and good manufacturing practice. That last standard matters: an approval covers not only the molecule and the trials, but also how the specific product is made.

What an approval covers, and what it does not

An approval is narrower than most people assume. It covers a specific product, from a specific manufacturer, for the specific uses on its label. The label can be explicit about limits. The US label for tesamorelin, an approved peptide, states that it is not indicated for weight loss management and that its long-term cardiovascular safety has not been established.

It also does not extend to other products that contain, or claim to contain, the same compound. The FDA draws this distinction clearly in two settings.

Compounded medicines are prepared by pharmacies for individual patients whose needs an approved medicine cannot meet, for example because of an allergy to an ingredient. The FDA states that it does not verify their safety, effectiveness or quality before they are marketed. For compounded semaglutide and tirzepatide, it has received 990 and more than 730 adverse event reports respectively.

Products labelled "for research purposes" or "not for human consumption" are a third category. The FDA has sent warning letters to companies selling semaglutide, tirzepatide, retatrutide and similar compounds with those labels while also giving instructions for personal use.

Peptides that have not been through this path

Many peptides discussed online have never completed it. The FDA keeps a list of bulk substances nominated for use in compounding that may present significant safety risks. On the version current as of 22 April 2026, the entry for BPC-157 says compounded products containing it may pose a risk of immune reactions for some routes of administration, may have complexities with peptide-related impurities and with characterising the active ingredient, and that the FDA lacks sufficient information to know whether it would cause harm when given to humans. The nomination for its use in compounding was withdrawn.

The same page lists concerns for several other peptides, including a fragment of thymosin beta-4, GHK-Cu in injectable form, Semax, Selank, Epitalon, MOTS-c, CJC-1295 and ipamorelin. The concerns are mostly the same ones: the risk of immune reactions, impurities, and little or no human safety data. For sport, the anti-doping authorities go further. BPC-157 is prohibited at all times under the S0 category of the World Anti-Doping Agency list, for substances with no current approval by any government health authority for human therapeutic use.

Safety after approval

Approval is not the end of the safety question. Trials of a few thousand people cannot detect every rare harm. Phase 4 studies and pharmacovigilance, the systematic collection of adverse event reports once a medicine is in wide use, continue for as long as it is sold. BPOM describes this monitoring as part of its oversight of tirzepatide in Indonesia.

Labels change as knowledge grows. The retinopathy warning for semaglutide traces back to a signal in SUSTAIN-6, a trial designed to answer a different question. New uses need new evidence too: semaglutide gained its cardiovascular and kidney uses only after the SELECT and FLOW trials, and tirzepatide its cardiovascular use only after SURPASS-CVOT.

Three questions to ask about any peptide

1. Has any regulator approved it, and for what? Check the regulator's own site, not a seller's summary.
2. What kind of evidence exists? Animal studies, small uncontrolled reports and large randomised trials are not interchangeable.
3. Does the evidence describe the product in front of you? Trial results belong to the product that was tested, made the way it was made.