Understanding GLP-1 and its physiological role
GLP-1 (glucagon-like peptide-1) is a peptide hormone secreted by the gut when food is ingested. At the crossroads of metabolic pathways, it performs several key functions: regulating blood glucose by stimulating insulin secretion, slowing gastric emptying, and modulating the sensation of satiety – three elements that together participate in the body’s energy balance.
This triptych places GLP-1 at the center of energy balance management. Moreover, its interest as a therapeutic target is explained by its ability to directly influence metabolic syndrome, obesity and type 2 diabetes. Endocrinologists often refer to this hormone as the “missing link” in the treatment of obesity.
At the molecular level, GLP-1 acts on receptors located on the surface of beta cells in the pancreatic islets, central nervous system and digestive tract. It stimulates insulin release in a glucose-dependent manner, reducing the risk of hypoglycemia. The signal also passes through the brain, promoting the sensation of satiety – which partly explains why some patients report a reduction in compulsive eating shortly after starting treatment.
All these properties have led to the emergence of GLP-1 analogues in therapeutics. Sometimes, modulating a single brick in the hormonal system is enough to radically change the trajectory of a disease whose mechanisms were poorly understood until very recently.
Here we can delve deeper into the molecular mechanisms of GLP-1 and their impact on metabolism, particularly when coupled with the action of glucose-dependent insulinotropic polypeptide (GIP) in certain combination therapies.
GLP-1 analogues: a revolution in the treatment of obesity
The rise of GLP-1 analogues marks a break with the conventional approach to care for overweight people. Initially intended for type 2 diabetes, these drugs – Ozempic (semaglutide), Wegovy (semaglutide), Mounjaro (tirzépatide), Saxenda (liraglutide), Victoza (liraglutide), but also Trulicity (dulaglutide), Rybelsus (oral semaglutide), and Lixisénatide (Adlyxine) – are now prescribed well beyond the diabetic sphere.
They act as GLP-1 receptor agonists, mimicking the natural action of this digestive incretin: reduced appetite, slower gastric emptying, progressive weight loss and improved metabolic health factors, including blood glucose levels, blood pressure and even some cardiovascular parameters.
The large randomized STEP3, SURMOUNT-1 and SURPASS-2 studies report weight loss of between 15% and 20% over more than a year in obese or overweight patients, results that sometimes rival those observed after bariatric surgery. Semaglutide, for example, frequently achieves 15% weight loss, while tirzepatide even achieves up to 20% over 72 weeks in some recent protocols. It’s hardly surprising, then, that endocrinologists are seeing longer queues.
In France, around 550,000 patients were prescribed Ozempic in 2023, a figure that should exceed 700,000 in 2024, according to estimates by the Bordeaux Drugs-SafeR Centre and Epi-Phare. Today, Novo Nordisk and Eli Lilly are at the heart of the development of these revolutionary therapies.
The clinical evidence and therapeutic impact of GLP-1 analogues today represent a major advance, although their real efficacy and long-term benefit remain to be monitored in real life and according to individual patient profiles.
Our opinion
The arrival on the market of GLP-1 analogues arouses understandable excitement, but invites us to keep nuances in mind. Yes, the prospect of significant weight loss is seductive. However, we sometimes forget that these molecules are not a miracle solution: their real effectiveness depends on a multidisciplinary approach. For some patients, appetite is significantly reduced; for others, the effects are slow to show, fuelling discussion and expectations about their use.
A strategy that includes a healthy diet, appropriate physical activity (to prevent muscle loss/sarcopenia), psychological support and regular medical follow-up. Treatment alone cannot reverse the societal trend towards obesity.
A look in the rear-view mirror suggests caution. Significant pharmacovigilance episodes – Distilbene, Mediator, Isomeride – remind us that no innovation is immune to hazards. With the support of the ANSM and scientific committees (Comité permanent Pharmaco-surveillance), the French Assurance maladie is stepping up its monitoring and regulation of these prescriptions.
Prevention continues to occupy a central place: acting on the determinants of obesity (genetic, environmental, social, exposome, DOHaD) and on the behavioral level remains unavoidable, even if the arrival of new treatments sometimes gives the illusion of easier management.
Assessing the benefits and risks of GLP-1-based treatments
The increasing use of GLP-1 analogues calls for rigorous analysis of benefits and risks, on an individual and collective scale. The most notable benefits found in practice:
A stable and significant weight loss, an experience reported by the majority of patients, sometimes accompanied by a feeling of “disappeared appetite”.
A real improvement in cardiometabolic markers: better glucose regulation, lowered blood pressure, attenuated metabolic syndrome.
A reduction in comorbidities (arterial hypertension, metabolic steatohepatitis, associated cardiovascular diseases), now at the heart of endocrinology concerns.
In addition, there are adverse effects, sometimes severe, which require careful monitoring:
Disorders of transit: nausea, vomiting, diarrhea, constipation (so frequent that some patients speak of a “new relationship with the bathroom”).
Risk of acute pancreatitis, vigilantly reported during follow-up, but infrequent.
Ocular manifestations: optic neuropathies and potential aggravation of diabetic retinopathy.
Hypoglycemia in case of association with other hypoglycemic treatments or in case of monitoring error.
Muscle loss (sarcopenia), especially if physical activity is lacking in the overall approach.
Sometimes, persistent fatigue or taste disorders are reported in consultation, necessitating adjustment of care.
Pharmacovigilance, reinforced by cohorts such as Drugs-SafeR Bordeaux and Epi-Phare, today guarantees increased safety. Strict support and an individualized strategy are systematically recommended, with each profile requiring adjustments according to experience and tolerance. Sometimes, a simple dietary adjustment or resumption of physical activity is all that’s needed to limit certain side effects.
Mastering the benefits and side effects of GLP-1 treatments means easier day-to-day therapeutic choices for the medical team and the patient.
| Benefits | Side effects | |
|---|---|---|
| Lasting weight loss | Nausea, vomiting | |
| Cardiometabolic improvement | Digestive disorders | |
| Diminished appetite | Acute pancreatitis (rare) | |
| Reduction of comorbidities (HTA, steatohepatitis, metabolic syndrome) | Optic neuropathy, retinopathy | |
| Hypoglycemia (increased risk under combination) | ||
| Muscle loss (sarcopenia) without physical activity |
Ethical, economic and societal challenges of GLP-1 analogues
The mass deployment of GLP-1 analogues brings to the fore many challenges, far beyond medical considerations alone. Among them:
Accessibility: in France, the cost is around €300/month, reinforcing territorial and social inequalities in access to care. Not everyone can sustain this level of care, which directly affects public health economics.
Medicare reimbursement remains limited to cases of diabetes, fuelling a lively debate among professionals and patients alike. The Temporary Scientific Committee (CST), supported by the ANSM, is currently discussing extension to obesity.
Preventing misuse: use for cosmetic purposes or outside AMM (Autorisation de Mise sur le Marché) worries medical teams. Detour, facilitated by social networks and informal resale, are rekindling the debate on securing patient pathways.
Stigmatization and exclusion: several reports, including those by the WHO, remind us that therapeutic innovation must not reinforce the stigmatization of people suffering from obesity, who are already socially and psychologically vulnerable.
These treatments need to be integrated into a global approach, combining lifestyle hygiene, psychological support, social care and physical activity.
At regulatory level, the debate on long-term reimbursement and the question of the capacity of care structures to absorb demand without compromising quality remain open. The World Health Organization, the European Medicines Agency (EMA) and the FDA (Food and Drug Administration) are multiplying recommendations on the reasoned and equitable use of GLP-1 analogues.
== The ethical and economic choices surrounding new GLP-1 treatments profoundly question our collective values. ==
Reflection on the viability of reimbursement and equity criteria.
Increased vigilance against the stigmatization of obese people and management of the plurality of causes.
Strengthening therapeutic education programs, primary prevention and public information campaigns.
Question about the economic impact: the massive introduction of these drugs calls into question the system’s ability to remain sustainable, at a time when the prevalence of obesity is reaching over a billion people worldwide (source WHO).
Regulatory news and research prospects in France and internationally
The development of GLP-1 analogues is today accompanied by a rapid evolution in standards and innovations. In France, the ANSM plans to relax prescribing conditions from June 2025, supported by the Comité permanent Pharmaco-surveillance and university centers (e.g. University of Toulouse, University of Picardie Jules Verne, CHU Amiens, Montpellier, Limoges).
Internationally, the FDA (Food and Drug Administration) and the EMA (European Medicines Agency) are accelerating recognition of new indications for treatments combining GLP-1 and GIP action, such as tirzepatide, and for use in other pathologies, including addictology. Interest in addictology applications – reduction of alcohol craving or pathological eating impulses, for example – is the subject of publications in journals such as JAMA Psychiatry.
Advanced phase clinical trials, including phases III/IV launched in Europe from 2024-2025, are looking at visceral adiposity loss, the treatment of certain addictions, the GLP-1/GIP multi-agonist combination and the consolidation of overall metabolic health. Some protocols are also exploring the link between therapeutic efficacy and modification of the intestinal microbiota.
Pharmacovigilance – with almost daily monitoring of side effects thanks to the Epi-Phare and Drugs-SafeR Bordeaux cohorts – is taking on a central role: heightened vigilance is now the norm for these increasingly prescribed treatments.
Regulatory developments and advances in GLP-1 research are shaping a rapidly changing medical landscape, where multidisciplinary care, patient focus and innovation constantly intersect.
