Early access to innovative therapies is crucial to optimize patient management, especially in rare or severe diseases where therapeutic options are limited. Various programs, such as “compassionate use” and “expanded access”, have been implemented to address this need. In France, one of the main available regulatory mechanisms had long been “temporary utilization authorization” (TUA), either nominative or cohort based. Initiated in 1992, TUA allowed administration of treatments without Marketing Authorization (MA), whether pending, or refused, or never considered by the drug manufacturer [1]. TUA requests were evaluated by the National French Agency for Drug Safety (ANSM).

In 2021, the multiple existing regulatory frameworks, including TUA, were aggregated in two schemes: compassionate access for drugs without ongoing or planned clinical development in the indication, and early access program (EAP) for new treatments before MA granting or during the period between approval and reimbursement [2,3]. The “Haute Autorité de Santé” (HAS) is responsible for the assessment and approval of EAP, which is granted for a one-year period, renewable until the drug is launched. Under TUA and EAP prescriptions, physicians are required to collect predefined clinical data, which are regularly sent to the MA owner, analyzed, and submitted to Health Authorities (HAS and ANSM).

In 2024, obesity affects 18% of the adult population in France, representing approximately 10 million people according to a large national epidemiological survey [4]. Class 3 obesity is the fastest-growing category, rising from 1.2% of the population in 2012 to 1.9% in 2024 (+ 60%) [4], characterizing approximately 1 million people. The higher the BMI, the more frequent the associated co-morbidities: in the French survey, 35% of patients with a BMI > 40 kg/m2 reported high blood pressure, 30% obstructive sleep apnea syndrome (OSA) and 22% dyslipidemia [4]. For these patients, the use of all strategies available for obesity management, including bariatric surgery and pharmacotherapy, should be considered. Semaglutide is a once-weekly subcutaneously administered GLP-1 analogue, initially approved at the dose of 0.5 mg and 1 mg for the treatment of type 2 diabetes mellitus (T2DM) under the trademark name Ozempic® [5]. It has since been developed and approved at higher dosage (2.4 mg weekly) to treat people living with either overweight or obesity due to its mechanism of action on appetite regulation, resulting in decreased food intake. Semaglutide 2.4 mg was approved together with diet and physical activity in adults with a BMI of 30 kg/m² or greater or a BMI of at least 27 kg/m² who have weight-related health problems, in January 2022 under the trademark name Wegovy® [6]. It is also approved for adolescents from 12 years of age whose BMI is at or above the 95th percentile for their age and gender (obesity) and who weigh more than 60 kg. In the STEP randomized clinical development program, including people with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² with weight-related comorbidities, semaglutide 2.4 mg demonstrated statistically significant improvements in weight loss (Treatment policy estimand: mean reduction of 15%. Trial product estimand: mean reduction of 17%) and in proportions of responders (weight loss above 5%, 10%, 15% of initial weight) compared to placebo or liraglutide 3 mg, in patients with or without diabetes, and in various populations including those originating from Asian countries [[7], [8], [9], [10], [11], [12], [13], [14]]. In addition to short-term effects, the benefits of maintenance therapy were shown in the STEP 4 trial, where patients randomized to placebo after 20 weeks of therapy gained a mean 7% of body weight after 48 weeks, while those who continued semaglutide 2.4 mg lost another 8% of body weight during the same period [15]. In the SELECT study which included patients with established cardiovascular disease and overweight or obesity but without T2DM, once-weekly s.c. semaglutide 2.4 mg showed its superiority versus placebo with a 20% reduction for the 3-point major adverse cardiovascular event (3-P MACE) including death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke [16]. Yet, real-world data remain scarce, especially in a population composed of people living with severe obesity and treated comorbidities.

We utilized data from the TUA and EAP to gain insights into the first cohort of patients treated in France outside of a clinical trial. This analysis highlights the real-world applicability and safety profile of semaglutide 2.4 mg in a more complex and severely obese population compared to patients included in the STEP program.