How GLP-1 weight-loss medicines work.

Weight is regulated, not just chosen

Your brain defends a body weight. When you diet, hunger hormones rise and the hormones that signal fullness fall. Your body also burns slightly less energy. That is why most diets work for a few months and then stall or reverse. Willpower is fighting biology.

The gut hormones involved

After a meal, the gut releases GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). Together they:

• Signal fullness to the appetite centres of the brain, so you are satisfied sooner and think about food less
• Slow how quickly the stomach empties, so fullness lasts longer
• Help the pancreas release insulin when blood sugar rises, and dampen glucagon

Natural GLP-1 lasts only minutes in the blood. The medicines are engineered versions that last about a week, so a single weekly injection keeps the signal steady.

The main medicines

What the trials showed

In the large trials, people combined the medicine with diet and activity advice and were followed for well over a year:

• Semaglutide 2.4 mg (STEP 1): average loss of 14.9% of body weight at 68 weeks, compared with 2.4% on placebo.
• Tirzepatide (SURMOUNT-1): average loss of 15% to 20.9% at 72 weeks, depending on dose, compared with 3.1% on placebo.

Semaglutide 2.4 mg also reduced major heart attacks, strokes and cardiovascular deaths by about 20% in people with heart disease and excess weight who did not have diabetes (SELECT trial). For a 100 kg person, a 15% loss is 15 kg. That is enough to change blood pressure, blood sugar, joint pain and sleep apnoea.

What they cannot do

• They do not replace food quality or movement. Eating less without enough protein, and without strength training, means losing muscle along with fat.
• They are not a short course. Weight tends to return when they are stopped. See what happens when you stop.
• Responses vary. Some people lose much more than average and some much less.
• They have side effects. These are usually mild stomach symptoms, but not always. See side effects and safety.

Why the dose goes up slowly

Both medicines start at a low dose and step up every four weeks or so. This lets the gut adapt and keeps nausea manageable. Rushing the steps is the most common reason people feel unwell and give up. The pace should be set by a clinician who reviews how you are doing.