While nearly one in two people in France is affected by excess weight, finding effective medical solutions to fight obesity has become a major public health issue.
Authorized on the French market only since 2024, these treatments, initially intended to fight diabetes, raise many questions.
As a dietitian, I am often asked questions about how these highly promising treatments work. Here I explain what I have gathered on the subject, to understand their mechanisms and their uses, and to help you form an informed opinion.
A quick reminder: their prescription is strictly regulated in France. They are reimbursed only under certain conditions, and must under no circumstances be considered simple slimming food supplements.
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GLP-1: a key hormone for weight management
A hormone for weight balance
Glucagon-like peptide-1 (GLP-1) is an intestinal hormone produced after meals.
Unlike glucagon, a pancreatic hormone that releases glucose into the blood when it is lacking, GLP-1 helps regulate blood sugar and eating behavior.
In people who are overweight or have diabetes, the secretion of GLP-1 is often decreased, which disrupts satiety, sugar regulation, and food-related sensations.
The three major actions of GLP-1
Regulate blood sugar
GLP-1 stimulates insulin when blood sugar rises and slows the production of glucagon.
The result: a drop in blood sugar and fewer blood sugar spikes.
Slow down digestion
Indeed, the GLP-1 hormone works to slow gastric emptying, which:
- prolongs satiety
- reduces hunger
- reduces the glycemic load of the meal
Act on the brain and reduce appetite
Another function, GLP-1 helps reduce the feeling of hunger by acting indirectly on the hypothalamic-pituitary center. This is a major regulatory center located in the brain.
What actions can be expected from GLP-1 agonists?
Mimic the natural hormone
Several researchers, by studying these mechanisms, have gone on to formulate GLP-1 agonists. The aim is to mimic the natural hormone, but with a longer duration of action.
Specifically: they bind to the same receptors and enhance the natural effects of GLP-1. As a result, blood sugar is better regulated, digestion is slower, and appetite is reduced.
Three molecules are now available in France.
Liraglutide
It is the first GLP-1 analogue approved for weight loss. It is administered every day, unlike the others, because its duration of action is shorter.
Known by the name Saxenda®, it works by boosting insulin production, reducing glucagon secretion, and slowing gastric emptying.
Semaglutide
Administered only once a week, it is also available under the name Ozempic® for diabetes or Wegovy®.
It is thought to have greater affinity for the GLP-1 receptors in the pancreas, and those in the brain.
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Tirzepatide
More recent, it is rather a dual GLP-1 / GIP agonist, which means that it simultaneously stimulates two incretin hormones. At the pharmacy, it is sold under the name Mounjaro®.
Its administration is monthly, like semaglutide, and reserved for specific cases of type 2 diabetes.
What do clinical studies show about GLP-1 analogues?
On the plus side, the scientific literature now documents the effects of this new generation of anti-obesity treatments.
Clinical trials conducted with thousands of participants show significant weight loss and lasting metabolic improvements, as long as the treatment is continued.
Among these clinical studies that you can consult: SCALE for liraglutide, STEP for semaglutide and SURMOUNT for tirzepatide.
Cross-referencing the results, GLP-1 agonists allow, on average, for a loss ranging between 8 and 22% of body weight, depending on the molecule used, the dose, and the duration of treatment.
To sum up, these treatments improve weight loss and other metabolic parameters such as:
- blood glucose and insulin resistance
- waist circumference and visceral fat
- reduction of cardiovascular risks
- reduction of inflammatory markers
- regulation of appetite, cravings, and total energy intake
What you can remember about these molecules: their effectiveness in helping with weight loss would be based on four actions. The hypoglycemic action, the action on gastric emptying, and the action on the brain.
The limitations of these weight loss treatments
However, it should be emphasized that 10% of patients would not lose weight on average, or would lose very little.
Another fact that seems just as important to highlight: a regain of the lost weight is observed during the year following the end of treatment. On average, 50 to 70% of the weight lost is regained.
This suspensive effect of the treatment shows, in my view, its limits : the hormonal effects stop as soon as the treatment is discontinued, without consolidation of lifestyle habits.
I would also like to draw your attention to the relatively frequent side effects, particularly at the start of treatment:
- nausea, diarrhea, constipation, reflux
- fatigue, headaches
- digestive discomfort related to slowed gastric emptying
- loss of muscle mass
Most of them are temporary and justify progressive dosing in order to avoid them. However, some patients must reduce or stop the treatment completely.
In rarer cases, pancreatitis, hypoglycemia or persistent digestive disorders have been observed, hence the importance of regular medical follow-up.
My opinion on GLP-1 treatments
As a dietitian, I insist: these antidiabetic and anti-obesity medications are not suitable for everyone.
Weekly injections can become tiresome and be a barrier to good adherence to treatment over several years.
Then, as with any weight-loss process, the risk of yo-yo dieting is real.
Yes, GLP-1 medications can be an effective tool to support weight loss, and I find them interesting. But here’s what I think: they cannot replace a comprehensive approach that includes nutrition education, regular physical activity, and psychological support.
Sources and scientific studies
Xavier Pi-Sunyer, Arne Astrup, Ken Fujioka, Frank Greenway, Alfredo Halpern, Michel Krempf, David C W Lau, Carel W le Roux, Rafael Violante Ortiz, Christine Bjørn Jensen, John P H Wilding; SCALE Obesity and Prediabetes – A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management, 2015, New England Journal of Medicine
Domenica Rubino, Niclas Abrahamsson, Melanie Davies, Dan Hesse, Frank L Greenway, Camilla Jensen, Ildiko Lingvay, Ofri Mosenzon, Julio Rosenstock, Miguel A Rubio, Gottfried Rudofsky, Sayeh Tadayon, Thomas A Wadden, Dror Dicker; Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial, 2021, JAMA
Louis J Aronne, Naveed Sattar, Deborah B Horn, Harold E Bays, Sean Wharton, Wen-Yuan Lin, Nadia N Ahmad, Shuyu Zhang, Ran Liao, Mathijs C Bunck, Irina Jouravskaya, Madhumita A Murphy; Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial, 2024, JAMA
John P H Wilding, Rachel L Batterham, Melanie Davies, Luc F Van Gaal, Kristian Kandler, Katerina Konakli, Ildiko Lingvay, Barbara M McGowan, Tugce Kalayci Oral, Julio Rosenstock, Thomas A Wadden, Sean Wharton, Koutaro Yokote, Robert F Kushner; STEP 1 Study Group – Weight regain and cardiometabolic effects after withdrawal of semaglutide, 2022, Diabetes Obesity and Metabolism
