Long-Term Use of the Weight-Loss Drug Liraglutide in Obese Teenagers in Switzerland

Obesity is a health condition that is associated with numerous metabolic and psychological complications in the long term [1,2]. While the prevalence of overweight and obesity among children and adolescents in high-income countries has stabilized at a high level, it is on the rise in low-income countries [3,4]. The stabilization or even a slight decrease in this trend has recently been demonstrated for Switzerland [5]. Moreover, the leading role of migration in the increase in overweight and obesity has also been demonstrated [6]. Children with parents from Southern European countries have a 2.5-fold higher risk of being overweight in Switzerland [6,7].

Obesity is increasingly recognized as a complex, multifactorial chronic disease that arises from the interplay of biological, behavioral, environmental, and psychosocial determinants, rather than from a single causal pathway [8]. The treatment of adolescents with overweight and obesity places high demands on all those involved and is often accompanied by little success, also with regard to lasting changes [8]. Although lifestyle-based interventions typically achieve only modest reductions in body weight, their overall effectiveness remains limited [1]. The use of GLP-1 (Glucagon-like Peptide-1) receptor agonists (e.g., Liraglutide and Semaglutide) together with lifestyle interventions has shown greater weight loss than conventional non-pharmacological treatment [9,10,11,12]. GLP-1 receptor agonists reduce body weight primarily by activating hypothalamic satiety pathways, delaying gastric emptying, suppressing glucagon secretion, and lowering food intake, thereby improving both energy balance and metabolic control [13]. Whether metabolic parameters can also be improved in children and adolescents is the subject of current studies [14]. However, the side effect profile in children and adolescents appears to be largely favorable and mainly related to nausea [14,15,16]. Indications of an increased risk of suicidal behavior have not been confirmed to date [17,18]. The data available for children under the age of 12 is very limited but also shows efficacy in terms of reducing weight and waist circumference [19,20]. The prescription rate has increased significantly in children and adolescents in the United States, although clear ethnic differences have been observed [21].

In Switzerland, both Saxenda^® (Liraglutide, since June 2023) and Wegovy^® (Semaglutide, since May 2025) are reimbursed for adolescents ≥12 years with ≥60 kg body weight and obesity defined by IOTF [22] age- and sex-specific BMI thresholds equivalent to an adult BMI ≥ 35 kg/m² [23,24]. Prescription of either drug is restricted to pediatric endocrinologists or certified pediatric obesity centers and requires prior insurer approval, documented calorie restriction, structured physical activity, and three-monthly follow-up. Wegovy^® must be discontinued if BMI or BMI z-score does not improve by ≥5% after 28 weeks [23], whereas Saxenda^® must be stopped if BMI fails to improve by ≥4% after 12 weeks at the maximal tolerated dose [24].

In this retrospective longitudinal, non-interventional real-life data study, we present outcomes from 22 adolescents treated with Saxenda^®. Based on the pivotal trials, we anticipated a comparable reduction in BMI. In the SCALE Kids trial by Fox et al. [9], children aged 6 to <12 years with obesity showed a mean BMI reduction of −5.8% at 56 weeks compared to placebo. Similarly, in the adolescent trial by Kelly et al. [10], Liraglutide resulted in a mean BMI-SDS reduction of −0.22 after 56 weeks.

In all but three patients the dose was titrated up to 3 mg; in one patient the maximum dose reached was 1.8 mg, and in two patients the maximum dose was 2.4 mg. The average treatment duration was 8.2 months, with a range of 1 to 18 months. The median BMI-SDS decreased from +2.63 (IQR +2.4 to +2.8, total range +2.2 to +3.3) at treatment initiation to +2.4 (IQR +2.2 to 2.6, total range +1.9 to +3.3) at the last follow-up (Figure 1). The median intra-individual reduction in BMI-SDS was −0.20 SDS (IQR −0.28 to −0.10, full range −1.0 to 0.1), which was highly significant (Wilcoxon signed-rank test p = 0.0003) with a large effect size (r_b = −0.77). The 95% CI for r_b was −0.86 to −0.63.

In the patients continuing therapy (9 out of 22 patients, representing 41%), BMI-SDS decreased from +2.59 (IQR +2.4 to +2.8, total range +2.2 to +2.9) to +2.08 (IQR +1.9 to +2.4, total range +1.4 to +2.7). Thus, in those continuing treatment, the median intra-individual reduction in BMI-SDS was −0.51 SDS.

In practical terms, a reduction of −0.5 SDS in body weight can represent a clinically meaningful change. For instance, Patient 19 in our cohort initially presented with a body weight of 105.8 kg. After approximately six months, her weight had decreased to 85.8 kg, corresponding to an absolute loss of 20.0 kg. This substantial reduction is reflected in the SDS metric as a shift of −0.5, underscoring how even a seemingly moderate change in standard deviation units may translate into a pronounced and tangible improvement in individual patients.

However, Saxenda^® was discontinued in 13 patients for different reasons (Table 1). No serious adverse events were reported. In the patients who discontinued therapy, BMI-SDS changed from +2.63 (IQR +2.4 to +2.8, total range +2.4 to +3.3) at baseline to +2.58 (IQR +2.4 to +2.7, total range +2.1 to +3.3) at the last visit. There were no significant differences in age, baseline BMI-SDS, or sex distribution between patients who continued treatment (mean age 14.8 years, mean BMI-SDS 2.59, sex ratio F/M = 4/5) and those who discontinued therapy (mean age 15.0 years, mean BMI-SDS 2.65, sex ratio F/M = 5/8). Those who discontinued received therapy for a mean of 7.6 months (range 1–15 months), while patients who remained in treatment were on therapy for a mean of 9.7 months (range 4–18 months).

Regarding the Swiss reimbursement criterion of a ≥4% BMI reduction at 4 months, 20 patients completed at least four months of therapy, of whom 19 met the criterion and one did not.

In this real-life cohort, we were able to show the effectiveness of GLP-1 receptor agonist therapy with Liraglutide/Saxenda^® in adolescents in combination with lifestyle counseling. The efficacy, measured by the intraindividual change in BMI-SDS before treatment and at the time of evaluation (last follow-up visit), corresponds to the published results from the pivotal phase 3 trial [10]. Although the observed BMI-SDS reduction is numerically similar to that reported by Kelly et al., differences in study design—including the absence of a placebo control—as well as the wide range of treatment durations and the shorter follow-up compared with the pivotal 56-week trial limit direct comparability and the assessment of long-term efficacy [10]. In those continuing treatment, the reduction in BMI-SDS was −0.51 SDS. Our data allow for this distinction, which has not been clearly differentiated in previously reported cohorts.

In contrast, the Spanish real-world study reported a substantially greater mean BMI-z reduction of −1.09 ± 0.24 after a similar treatment duration, likely reflecting the combination with intensive lifestyle interventions and the higher baseline obesity severity in their cohort [27]. Although intensive lifestyle interventions represent the recommended standard of care, they are not uniformly accessible or sustainable in routine clinical practice, which this real-world study was designed to reflect. This finding also highlights the considerable interindividual variability in treatment response and emphasizes the need to identify clinical or behavioral predictors of good response. The greater efficacy reported in the Spanish study may in part relate to a higher concentration of such responders within their intensively managed cohort.

However, our observation period is shorter than the 56 weeks in the Kelly et al. study [10], meaning that persistent weight losses are possible. In contrast to the marked BMI-z reduction in the Spanish cohort, the single-center Qatari study by Dauleh et al. found no significant changes in BMI or BMI-SDS after 72 weeks among the 12 patients who completed treatment (45% drop-out rate) [28]. The Slovenian real-world study reported a modest six-month BMI-SDS reduction (−0.28 SDS), comparable to our findings [29]. In the Austrian HBLT study, adolescents treated with liraglutide in combination with structured lifestyle therapy showed a mean BMI reduction of −2.7% (−6.24% among continuers). This is comparable to the modest BMI-SDS decrease observed in our cohort, though direct comparison is limited by differing outcome measures and study designs [30].

Moreover, obesity research is complicated by placebo and nocebo effects [31], and the Hawthorne effect may similarly influence weight-loss motivation during scheduled follow-ups [32], although these factors remain insufficiently explored in adolescents. Structured pediatric obesity programs (without GLP-1 receptor agonists) are expensive and yield only limited weight reduction, which restricts their practicality in everyday healthcare [33]. In our cohort, lifestyle counseling—including nutritional guidance—was therefore not delivered through a structured program but as an individualized multicomponent approach integrated into routine clinical consultations by the pediatric endocrinologist. While this introduces variability in counseling intensity, it reflects the real-world clinical setting in which approaches to lifestyle counseling may differ across centers and practitioners.

With regard to the side effect profile, the typical symptoms of nausea were observed. No other new symptoms or serious unexpected side effects occurred during the observation period. In four of our 22 patients, nausea led to discontinuation of treatment (approx. 23% of study participants), while mild nausea symptoms were described in 64.8% of Kelly et al. [10]. Gastrointestinal side effects were also the most common in the study by Danne et al. [16,28].

However, the proportion of treatment discontinuations is remarkably high, underscoring the need for thorough pre-treatment counseling to inform patients about expected, generally mild symptoms and their often-transient nature. Furthermore, general measures to reduce nausea should always be integrated into treatment information and initiation (e.g., advice on eating habits, food composition and lifestyle) [34]. This includes eating smaller portions more slowly, reducing fatty foods and stopping eating when satiated. Our cohort showed a dropout rate of 59% (13 of 22 patients), which is higher than the 41% reported in the Austrian HBLT study [30] and the ~45% observed in the Qatari cohort [28]. This aligns with findings in adults, where discontinuation rates of GLP-1 receptor agonists reached 50.3% [35]. The factors underlying treatment adherence versus discontinuation in adolescents remain unclear and warrant further investigation.

Regarding the Swiss reimbursement criterion of a ≥4% BMI reduction at 4 months, 19 of 22 patients met this requirement; only three failed to reach the threshold, two of whom discontinued treatment before three months—highlighting that treatment success depended more on persistence than on reimbursement-related restrictions. While the ≥4% BMI reduction threshold is administrative, BMI-SDS reduction remains a clinically relevant surrogate associated with improved health trajectories in adolescents with obesity.

Notably, the ethnic composition of our cohort does not reflect the general demographic distribution in Switzerland and at our center but is skewed towards adolescents with Southern European roots (68%). This pattern aligns with previously reported disparities in the prevalence of overweight and obesity within Swiss society [5,6,7,35]. Understanding the demographic profiles associated with current GLP-1 receptor agonist prescribing patterns may support the development of more tailored therapeutic guidance and follow-up [21]. Importantly, previous work has shown that the disproportionately high prevalence of obesity among children of Southern European origin in Switzerland is largely genetically determined rather than explained by cultural, socio-economic, or dietary factors [6].

This study is limited by its small sample size and retrospective design, which restrict the strength and generalizability of the findings. The absence of predefined criteria for treatment success and the heterogeneity in treatment duration introduce additional variability.

From our point of view, it would be worthwhile to study the pre-therapy factors that could correlate with treatment effectiveness. These could potentially include personality types, cognitive characteristics, demographic and ethnic factors, social and environmental factors or genetic aspects. This requires well-designed prospective studies with a diverse patient population and longer follow-up [36]. Other GLP-1 receptor agonists, such as Semaglutide/Wegovy^® [11], could have better effects in adolescents [37]. Identifying predictors of treatment response will be key to optimizing and personalizing GLP-1 receptor agonist therapy in this population.

In summary, treatment with GLP-1 receptor agonists in our cohort was effective in 41% of the adolescents and the side-effect profile was consistent with expectations, albeit with a high drop-out rate. In our setting, lifestyle counseling was not delivered within a structured program but provided as a component of routine visits by the attending pediatric endocrinologist. Further evidence is needed to support broader use in this population, and in the meantime, emphasis should be placed on addressing the reasons for discontinuation through clear pre-treatment counseling and strategies to mitigate nausea.