I get asked this a lot. Some people want to know if it works, others if it is harmful, others if it is worth the price. I went to see what the studies say, what the medicines agencies say and what is going on in Portugal.
GLP-1 is a hormone your gut releases when you eat. It tells the pancreas to release insulin, makes the stomach empty more slowly and sends the brain the signal that you have had enough. Ours lasts less than two minutes in the blood.
GLP-1 analogues are manufactured versions of this hormone, changed so they last much longer. Semaglutide, for example, lasts about a week, which is why it is given as one injection a week.
That is where the effect on weight comes from: you are less hungry, you feel full sooner and you end up eating less.
Semaglutide. This is Ozempic (for type 2 diabetes), Wegovy (for obesity) and Rybelsus (a tablet for diabetes). In July this year the European Commission also approved Wegovy as a tablet, the first oral GLP-1 for weight loss in Europe.
Tirzepatide. This is Mounjaro. Besides GLP-1, it acts on another gut hormone, GIP. It is approved for diabetes and for obesity.
Liraglutide. This is Saxenda. It is older, it is taken every day and it leads to less weight loss than the other two.
Orforglipron. A tablet approved in the United States in April this year, under the name Foundayo. It is not yet sold in Europe.
Retatrutide. Still being studied. It acts on three hormones instead of one or two. The application for approval in the United States is planned for 2027.
The study that launched Wegovy is called STEP 1. Almost 2000 adults with overweight or obesity, all given advice on food and exercise. Half took semaglutide, the other half an identical injection with nothing in it. After 68 weeks, those on the medicine had lost on average 14.9% of their body weight. The others lost 2.4%. Half of those on semaglutide lost 15% or more.
In the Mounjaro study, SURMOUNT-1, the highest dose gave an average loss of 20.9% over 72 weeks, against 3.1% in the group without the medicine.
In 2025 the first study putting the two head to head came out, with 750 people. Tirzepatide gave 20.2% weight loss and semaglutide 13.7%.
The Wegovy tablet gave close to 17% over 64 weeks. Orforglipron gave 12.4% over 72 weeks. Retatrutide, in its first large study, reached 28.3% over 80 weeks at the highest dose.
These numbers are averages. Some people lose a lot more and some lose little.
The SELECT study followed 17,604 people with heart disease and excess weight, without diabetes. Over about three and a half years, those who took semaglutide had 20% fewer heart attacks, strokes and deaths from cardiovascular causes than those who did not.
The most common ones involve the stomach and gut. In STEP 1:
Some people also get stomach pain, bloating or reflux.
They show up mostly at the start and every time the dose goes up, which is why the dose starts low and rises over several weeks. With Wegovy, the final dose is reached after 16 weeks. Nausea usually settles down with time. In STEP 1, 7% of people stopped the medicine because of side effects, against 3% in the other group.
There are also rarer effects:
There are also three practical precautions:
If a person ate exactly the same without taking anything, would they lose the same weight?
To answer that for sure, you would need a study with two groups eating the same calories, controlled to the gram, for months. One on the medicine, one without. I did not find one.
Most likely it does not exist for two reasons. To control calories to the gram, people would have to live for months in a research unit eating only what they were given, because at home nobody can count exactly what they eat. That is very expensive and hard to keep going. And the medicines agencies do not ask for it: to approve a drug, it is enough to show that it leads to more weight loss than placebo and that it is safe.
The studies that do exist all point the same way.
In a study with semaglutide, resting metabolism, adjusted for lean mass, was the same as in those who took placebo. People ate less and felt less like eating.
In a 2025 study with tirzepatide, energy expenditure dropped by what would be expected for the weight people lost, no more and no less.
In another study, people with fatty liver lost the same weight, some with liraglutide and others with diet and exercise alone. Body composition changed the same way in both groups. Those on the medicine had better blood sugar and blood fat values.
With what we know today, the weight comes off because people eat less.
When you lose weight, you lose fat and you lose lean mass. Lean mass includes muscle, but also water and organs.
In STEP 1, about 39% of the weight lost was lean mass. In SURMOUNT-1 it was about 25%. In these studies there was no strength training and no protein target, and anyone who loses a lot of weight eating little, without training, always loses some muscle.
Published reviews recommend strength training and between 1.2 and 1.6 g of protein per kilo of body weight per day for people on these medicines. Because you are less hungry, reaching that protein takes more work than it seems. And with little appetite it is easy to start eating too little, without enough protein, fruit and vegetables.
In the STEP 1 extension, one year after stopping semaglutide, people had regained two thirds of the weight they had lost. Blood pressure, blood sugar and cholesterol also went back close to where they were.
In January this year the BMJ published an analysis of 37 studies. The authors estimated that, after stopping semaglutide or tirzepatide, people return to their starting weight in about a year and a half. They gain around 0.4 kg a month, four times faster than people who lost weight with diet and exercise alone.
These studies measure what happens when people stop. They do not measure why. My reading is the same one I make for any diet: if nothing changed in the way you eat, in the choices you make and in your relationship with food, sooner or later you end up back where you started.
You need a prescription. In Europe, Wegovy and Mounjaro for weight loss are indicated for adults with a body mass index of 30 or more, or 27 or more with a weight-related health problem, such as diabetes, high blood pressure, high cholesterol or sleep apnoea. Outside these criteria, for someone who just wants to lose a few kilos, they are not approved.
For obesity there is no state reimbursement. Ozempic is only reimbursed for type 2 diabetes. Infarmed, the Portuguese medicines authority, is preparing a special reimbursement scheme for obesity, but in May there was still no date.
You pay the full price. Since June, Wegovy costs about 174 euros a month at the 1.7 mg dose and 199 euros at 2.4 mg. Mounjaro ranges from about 180 to 430 euros a month, depending on the dose.
Online you will find pens and vials sold without a prescription, and some people sell "microdoses". Infarmed reminds people that these medicines can only be bought in pharmacies. Fake Ozempic pens have already circulated in the European Union, which may not contain the substance or may contain others they should not. As for microdoses, there is no study showing they work.
For people with obesity, they are today the most effective medicines for losing weight without surgery. The studies are large, they were done in thousands of people over years, and the side effects are well described.
Anyone taking them still needs to train strength, reach their protein and learn how to eat.
If you are thinking of taking them, talk to your doctor, gather this information and make the decision yourself. I have left you here what I found.
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