Peptides & GLP-1 · Explainer
GLP-1 Drugs, Explained Without the Hype
Semaglutide and tirzepatide are the most effective weight-loss drugs ever brought to market. They are also prescription medicines with real side effects and a large grey market growing around them.
By Julien Malet, · Updated 2026-09-08
GLP-1 receptor agonists are the biggest thing to happen to metabolic medicine in a generation, and the conversation around them has become almost useless — split between people selling them and people frightened of them.
Here is what they are.
What GLP-1 actually is
Glucagon-like peptide-1 is a hormone your gut releases after you eat. It does several things at once: it prompts insulin release, slows how quickly your stomach empties, and signals satiety to your brain.
Your own GLP-1 breaks down within minutes. The drugs are engineered versions that resist that breakdown and last long enough to dose weekly. That is the whole trick — not a new mechanism, a durable version of one you already have.
The two that matter
Semaglutide (Ozempic and Rybelsus for type 2 diabetes; Wegovy for weight management) targets the GLP-1 receptor. In the STEP trials, semaglutide 2.4 mg weekly produced mean weight loss around 15% of body weight over 68 weeks alongside lifestyle intervention.
Tirzepatide (Mounjaro for diabetes; Zepbound for weight management) targets GLP-1 and GIP, a second gut hormone receptor. In the SURMOUNT trials it produced mean weight loss in the low-to-mid 20% range at the highest dose over 72 weeks — meaningfully more than semaglutide, with a similar side-effect profile.
For context: before these drugs, a weight-loss medication producing 5–10% was considered a success.
What the trials also found
- Gastrointestinal side effects are the norm, not the exception. Nausea, vomiting, diarrhoea and constipation are common, usually worst during dose escalation, and the main reason people stop.
- A meaningful share of the weight lost is lean mass. This is expected in any substantial weight loss, but it matters more here because the loss is fast. Resistance training and adequate protein are the countermeasures, and they are the single most actionable thing in this article. See GLP-1s and muscle loss.
- Stopping tends to mean regain. In the STEP 4 extension, people who withdrew regained a large share of lost weight over the following year. These are treatments for a chronic condition, not a course of antibiotics.
- Rarer risks exist, including pancreatitis, gallbladder disease and a boxed warning for thyroid C-cell tumours based on rodent data. There are also documented cases of severe gastroparesis.
The grey market
Because branded supply has been constrained and cash prices are high, a large market has grown in compounded semaglutide and tirzepatide, plus "research-grade" vials sold online with a not-for-human-consumption label.
This is the part worth being blunt about. Compounded versions are not FDA-approved, and the FDA has warned about dosing errors — some serious — arising from patients drawing up their own doses from vials, and about products using salt forms of semaglutide that are not the same ingredient as the approved drug. Grey-market peptides have no verified identity, purity or sterility.
When the FDA declared the semaglutide and tirzepatide shortages resolved, the legal basis for mass compounding narrowed considerably. Anything still being sold that way deserves scepticism.
More on sourcing in peptide safety and sourcing.
Who these are actually for
They are approved for specific indications — type 2 diabetes, and obesity or overweight with a weight-related condition. That is a clinical decision made with a clinician who can monitor you, not a decision to make from an article or a telehealth quiz that approves everyone.
If you are considering one, the useful preparation is knowing your numbers first: the biomarkers worth tracking are the ones a prescriber will actually look at.
This is not medical advice. These are prescription medications and this page is a summary of published trial evidence, not a recommendation.