Real-life use of liraglutide 3 mg in obesity management: The SAX-RL study

Abstract

In France, 17% of the adult population live with obesity,¹ a condition associated with increased risk of cardiovascular and metabolic diseases.² Limited pharmacological options are approved for obesity, although a weight loss of only 5%–10% can significantly reduce comorbidities.³ Recently, French guidelines have incorporated glucagon-like peptide-1 receptor agonists into obesity management strategies.⁴

In 2015, the European Medicines Agency (EMA) approved once-daily liraglutide 3 mg (Saxenda®) for adults with obesity (body mass index [BMI] ≥30 kg/m²) or overweight (BMI 27–30 kg/m²) with weight-related complications such as diabetes, hypertension, or obstructive sleep apnoea.⁵ The SCALE Obesity and Prediabetes trial in the same year demonstrated a mean weight loss of 8% at 56 weeks with liraglutide 3 mg, showing a 5.4% difference from placebo (95% confidence interval −5.8% to −5.0%).⁶ Efficacy was further supported by Phase 3 trials in the SCALE programme and real-world data, where ~60%–65% of patients achieved ≥5% weight loss, and 30% achieved ≥10% weight loss.^7-12

Nevertheless, adherence remained poor, and several patients failed to achieve weight loss. Real-world studies show that over half of patients discontinue liraglutide, whereas in major randomized studies, only 15%–30% interrupt therapy before completion.^6-12 There is limited understanding of how human behaviours and social determinants influence adherence to antiobesity treatments.

In March 2021, Saxenda was launched in France according to EMA indications but without reimbursement by the French health insurance system. This study investigates access and compliance to Saxenda during its first year on the market in a real-world population French population. Specifically, we sought to understand its effect on body weight and eating disorder as well as to identify potential obstacles contributing to treatment discontinuation in a real-world population.

SAX-RL is a monocentric retrospective study conducted at the Academic Center Specialized for Obesity Management (CSO) at Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, France. We identified all patients with at least one prescription of Saxenda between 1 March 2021 and 1 March 2022 in the hospital data repository. All patients are followed according to the clinical care routine, and personalized nutrition recommendations are consistently provided to each patient. The protocol was examined and approved by the local ethics committee. This study was conducted in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki).

The questionnaire assessed several outcomes: weight change from baseline to the time of completion; tolerance; compliance; and potential reasons for poor compliance. Additionally, it evaluated EPICES (Evaluation of Deprivation and Inequalities in Health Examination Centres) social deprivation score (scores ≥30 indicating precariousness) and the binge eating scale (scores ≥18 indicating significant binge eating disorder). Data collection spanned from 1 October 2022 to 30 November 2022. Multiple linear regression was used to investigate factors associated with treatment effectiveness, and logistic regression was employed to explain treatment continuation. Statistical significance was set at p < 0.05. All analyses were performed using R version 3.3.2.

A total of 168 patients received Saxenda from March 2021 to March 2022. Five declined participation and others did not proceed due to semaglutide switch (n = 4) or bariatric surgery plans (n = 2; Figure S1). In total, 153 patients provided baseline data and were invited to complete an online questionnaire. Ninety patients (90/153, 59%) completed it.

Table 1 presents the patients’ baseline characteristics. Most were women (65/90; 72%), aged 47.8 (±12.3) years with a BMI of 38.8 (±6.1) kg/m². Seventy-four percent (67/90) started Saxenda. A BMI of ≥40 kg/m² was reported in 40.3% of patients who started Saxenda compared to 21.7% of those who did not initiate Saxenda.

Social deprivation was observed in 48% of those who did not start the treatment compared to 18% of those who did start. Age, gender, and the presence of eating disorders seemed to be comparable.

Of the 67 patients who initiated treatment, 48 (72%) continued for less than 6 months, while 19 patients (28%) continued for more than 6 months. Those who continued longer achieved twice the median weight loss percentage (interquartile range) compared to those who did not continue (9.9% [5.7–22.5] vs. 5.7% [2.7–20.3]; Figure S2). Ninety percent (17/19) of patients who continued beyond 6 months reached the maximum 3-mg dose.

For the patients who never started treatment (26%; n = 23/90), the reasons included cost (65%; n = 15/23) and fear of side effects (35%; n = 8/23). For those who started but discontinued treatment (72%; n = 48/67), the reasons included cost (33%; n = 16/48) and side effects (31%; n = 15/48; Table S1).

The EPICES score showed a trend for being higher among patients who never started Saxenda (48%) compared to those who initiated and continued treatment (10.5%) or initiated and discontinued treatment (21%), although the difference was not significant (p > 0.05; Table 2).

Regarding treatment cost, 68% of patients who maintained treatment bought Saxenda for less than 180 euros per box, while only 37% of those who discontinued treatment did so. Multivariable analysis showed that continued treatment was associated with greater weight loss (p = 0.04), whereas the lowest dose of liraglutide (0.6 mg/day) was associated with less weight loss (p = 0.02). Other variables, such as gender, age, BMI, and Saxenda price, were not associated with weight loss magnitude (Table S2).

The SAX-RL study is the first to examine the real-life use of liraglutide 3 mg/day (Saxenda) in patients with obesity within the French context. This study showed that patients who started treatment were generally less socially disadvantaged than those who never started treatment, potentially indicating that they did not purchase the drug. Moreover, responses to questionnaires showed that the primary reason for not initiating Saxenda was its higher price, outweighing concerns about potential adverse effects. While some previous real-world studies have mentioned cost as a reason for treatment interruption, none has analysed its impact on treatment initiation. In a South-Korean study, only 3% stopped the treatment due to its cost.¹² This percentage may be underestimated considering the high rate of patients lost to follow-up without an identified cause. The Xensor study noted cost as a limiting factor in attainment of the maximum dose of liraglutide.⁸ SAX-RL showed a high rate of treatment interruption over time (n = 48/67; 71.6%), mainly due to its cost and related adverse events. In practice, the price of Saxenda in French pharmacies is free and extremely variable. Interestingly, 68% of the patients who continued the treatment over 6 months reported paying less than 180 euros per box for Saxenda compared to only 37% of patients who discontinued treatment before 6 months.

Our study provides a valuable insight into the impact of human behaviours and social determinants on adherence to antiobesity treatment, generating hypotheses about such influences. However, some limitations should be considered when interpreting our results. The study was conducted at a single centre, resulting in a small sample size; however, this allowed for the standardization of patient management practice. Response bias cannot be excluded from our study but we attempted to mitigate this by implementing rigorous quality control measures throughout the study period. Additionally, the study coincided with the COVID-19 pandemic, and we did not specifically evaluate data post-COVID. Investigating the specific impact of COVID-19 on the real-life usage of liraglutide remains an area of particular interest.

In conclusion, long-term Saxenda use in a real-world French setting led to significant weight loss. Failure to start or maintain treatment for over 6 months was linked mainly to social deprivation, higher costs, and medication-related adverse events.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Marc Goëau-Brissonnière, Aurélie Phan, Eleni Kourti, Nathalie Rassy, Estelle Lu, Charles Barsamian: none reported. Claire Carette: personal fees from Boehringer Ingelheim, Axis Santé, Pfizer, Bioprojet Pharma, Novo Nordisk, AstraZeneca, Novartis, Ipsen, MSD, Eli Lilly and Publicis Health, and nonfinancial support from Rhythm, Novo Nordisk, MSD, Novartis, Eli Lilly, Sanofi, AstraZeneca, Bristol-Myers Squibb, Abbott, Amgen, Vifor and Fresenius Kabi, outside the submitted work. Sébastien Czernichow: personal fees from Bariatek, NovoNordisk, Eli Lilly, Pfizer, Fresenius Kabi, Ipsen Pharma, Janssen-Cilag, Boehringer Ingelheim and Novartis. Co-founder of ALIFERT. Claire Rives-Lange: personal fees from Nestlé Health Science. Support for attending meetings: Nestlé home care and Fitform.