GLP-1 and metabolic medicine

GLP-1

Also called: glucagon-like peptide-1, GLP-1 receptor agonist

GLP-1 stands for glucagon-like peptide-1. It is a hormone made in the lower part of the small intestine, released when food arrives. It tells the pancreas to release insulin, slows the stomach down so meals last longer, and signals the brain that you are full. Drugs like Ozempic, Wegovy and Mounjaro mimic this signal at much higher levels.

What the hormone does naturally

GLP-1 is one of the body's incretin hormones. It is released by L-cells in the lining of the lower small intestine within minutes of eating. Its three main jobs are to trigger insulin release in response to glucose, slow gastric emptying so the stomach holds food for longer, and reduce appetite by acting on receptors in the hypothalamus.

Natural GLP-1 has a half-life of about two minutes. The body breaks it down quickly using an enzyme called DPP-4. This is why eating-induced satiety fades within a couple of hours and people get hungry again.

How GLP-1 receptor agonist drugs work

GLP-1 receptor agonists, often called GLP-1RAs, are synthetic versions of the hormone designed to last much longer than the natural one. Most current drugs are once-weekly injections. They produce a sustained signal where the natural hormone gives a short pulse. The result is a much stronger and longer-lasting reduction in appetite, slower stomach emptying, and tighter blood-sugar control.

The drugs in this class

  • Semaglutide: Ozempic (for type 2 diabetes), Wegovy (for weight management), Rybelsus (oral form for diabetes).
  • Tirzepatide: Mounjaro (diabetes), Zepbound (weight management). Acts on both GLP-1 and GIP receptors, hence dual agonist.
  • Liraglutide: Victoza (diabetes), Saxenda (weight management). Daily injection.
  • Dulaglutide: Trulicity (diabetes only).
  • Older or in-development: exenatide, lixisenatide, retatrutide (triple agonist, in trials), orforglipron (oral non-peptide, in late-stage trials).

Why these drugs cause gut symptoms

The same mechanism that makes GLP-1RAs effective for weight loss is what produces side effects. Slowed stomach emptying means food sits longer, so nausea and reflux are common in the first weeks. Slower movement carries through the rest of the gut as well, so constipation appears in roughly 1 in 5 to 1 in 4 users at higher doses (around 24 percent on Wegovy at 2.4 mg in the STEP trials, lower for tirzepatide and lower-dose semaglutide). Most symptoms settle within four to six weeks of reaching a stable dose, but flare again with each dose increase.

What GLP-1 is not

GLP-1 is not the same as insulin, even though it triggers insulin release. It is not a fat-burning drug. It works by reducing appetite and food intake, which produces a calorie deficit. Stopping the drug usually causes the appetite signal to return, and weight regain is common unless eating habits and lean muscle mass have been protected during treatment.

Common questions

Is GLP-1 a hormone or a drug?
GLP-1 is the natural hormone made in your gut. GLP-1 receptor agonists are the synthetic drugs that mimic it. People often use the term GLP-1 to mean both, but they are different things. The drugs last days; the hormone lasts minutes.
What is the difference between Ozempic and Mounjaro?
Ozempic uses semaglutide, which acts only on the GLP-1 receptor. Mounjaro uses tirzepatide, which acts on both the GLP-1 and GIP receptors. The dual mechanism produces stronger weight-loss effects in trials, with average loss of around 22.5 percent at the highest dose in SURMOUNT-1 (15 mg), compared with around 14.9 percent for semaglutide at 2.4 mg in STEP-1.
Can your body make more GLP-1 naturally?
Some foods and habits modestly increase natural GLP-1 release: protein-rich meals, soluble fibre, vinegar before meals, polyphenol-rich foods, and a longer overnight fast. The increase is small compared with what the drugs produce, but worth doing for general metabolic health.
How long do you stay on a GLP-1 drug?
Clinical guidance treats GLP-1 receptor agonists for weight management as long-term therapy in most cases, similar to medications for blood pressure or cholesterol. Stopping leads to weight regain in around two thirds of patients within one year. NICE in the UK funds tirzepatide for obesity for an initial two years, with review.

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