What is GLP-1? The fullness hormone behind the weight loss jabs

GLP-1 entered everyday conversation through the pharmacy door, to the point that many people asking "what is GLP-1?" assume it is a drug. It is first of all a hormone, one that every gut releases several times a day, at each meal. The treatments everyone is talking about do not even contain it: they imitate it.

Understanding GLP-1 means keeping those two things apart, the hormone and its copies. The first is part of the normal workings of digestion. The second are molecules designed in a laboratory, prescribed for type 2 diabetes and for weight management.

What is GLP-1, and what does the name mean?

GLP-1 stands for glucagon-like peptide-1. The name comes from its origin: the hormone is cut from the same large parent molecule as glucagon, another hormone involved in regulating blood sugar. The two do not have the same job, though, and their effects on blood glucose are opposite.

GLP-1 is made by L cells, scattered through the lining of the intestine and more numerous the further down you go towards the colon. They release it within minutes of a meal starting, in response to the nutrients passing over them.

One hormone, three recipients

GLP-1 acts mainly on the pancreas, the stomach and the brain. At the pancreas it prompts more insulin and puts a brake on glucagon. That signal has one precious feature, which is that it depends on the sugar level: it operates when blood glucose is high and fades as it comes down.

At the stomach, it asks for a slower pace. The meal leaves the stomach more gradually, nutrients reach the blood over a longer period, and the feeling of having eaten lasts longer. At the brain, lastly, it contributes to the fullness message, the one that makes you put your fork down.

GLP-1 belongs to the incretin family, the gut hormones that amplify the pancreas's response when sugar arrives by mouth and not directly into the bloodstream. It shares that family with GIP, less well known, which has gained in importance with the newest treatments. The standard reference on the subject is still the review by the Danish physiologist Jens Juul Holst in Physiological Reviews, 2007.

Two minutes, then nothing

Almost as soon as it is released, GLP-1 is destroyed. An enzyme found in the blood and on the surface of blood vessels, DPP-4, cuts it up within one to two minutes. Only a fraction of the hormone secreted reaches the general circulation in its active form.

That brevity makes sense: the signal is tied to the meal and switches off with it. It also long stood in the way of making a medicine. Injecting GLP-1 as it is would have achieved nothing, since it would have disappeared before it could act.

How a lizard opened the way to treatment

The solution came from a desert animal. In 1992 the American researcher John Eng described, in the Journal of Biological Chemistry, a molecule isolated from the venom of the Gila monster, a heavy-bodied lizard whose scientific name is Heloderma suspectum. This molecule, exendin-4, resembles GLP-1, activates the same receptor and resists breakdown far better. The first medicine in the family was derived directly from it.

Chemists then modified human GLP-1 itself to shield it from DPP-4 and hook it on to albumin, a blood protein that acts as its carrier. Liraglutide, then semaglutide, came out of that work. According to its product information, semaglutide has a half-life of about a week. From two minutes to seven days: everything that separates the hormone from the medicines is contained in that gap.

The medicines that mimic GLP-1

Doctors call them GLP-1 receptor agonists. The papers call them weight loss jabs or skinny jabs, a phrase even the regulator has taken to putting in its press releases. Four names come up most often in the UK.

All are prescription-only, most are given by injection, and all are licensed for use alongside a suitable diet and physical activity. On the NHS, NICE recommends semaglutide and tirzepatide for weight management on those same terms, with access being phased in for the people in greatest need. Their effect on weight has been measured in large trials: an average loss of 14.9% over 68 weeks with semaglutide 2.4mg in STEP 1, and up to 20.9% over 72 weeks with the highest dose of tirzepatide in SURMOUNT-1.

Those results have a flip side. The Wegovy product information classes nausea, vomiting, diarrhoea, constipation, abdominal pain, headache and fatigue as very common side effects, meaning they affect more than one person in ten, mostly while the dose is being stepped up. We give them a full guide to GLP-1 side effects. The effect also lasts only as long as the treatment, which is the subject of coming off Mounjaro or Wegovy. Whether such a treatment is appropriate, and which one, is a matter for a medical consultation.

The GLP-1 you make yourself

Quite apart from any treatment, GLP-1 release varies with what you eat. Protein stimulates it clearly. Fibre contributes by way of the gut bacteria, which turn it into molecules that L cells respond to. The length of the meal, sleep and physical activity play a part as well.

The effect remains that of a hormone with a two-minute life: a clearer fullness signal after the meal, nothing resembling the action of a medicine. We take stock in our piece on natural GLP-1, and the practical side, what to put on the plate when appetite is low, is in the GLP-1 diet guide.

What GLP-1 is not

It is not a nutrient: no food contains it. Nor is it an ingredient. The supplements, drops and patches labelled "GLP-1" do not hold any, and none is authorised to claim an effect on the hormone. The Advertising Standards Authority has ruled against several adverts that suggested otherwise. The letters on the pack express a commercial intention, as our guides to GLP-1 supplements and GLP-1 patches explain.

Nor is it the "skinny hormone" of some headlines. GLP-1 is one of many signals that regulate appetite, along with ghrelin, leptin, peptide YY and others. Its name became famous because someone worked out how to copy it. Physiology itself does not come down to a single molecule.

This article is for information only and is no substitute for advice from a healthcare professional. Never change your treatment without talking to your doctor.