Endocrine Abstracts

Introduction: The prevalence of obesity, a chronic disease with significant morbidity, has rapidly increased in recent decades. Semaglutide, an injectable glucagon-like peptide-1 agonist, has gained global popularity after its approval for weight management in 2021. All studies have reported marked variability in semaglutide response, with a small proportion of patients (10-16%) showing inadequate response. Data about the predictors of poor response to semaglutide for weight loss is lacking.

Methods: This is a retrospective case review of patients treated with semaglutide for weight loss in an endocrine clinic in Athens, Greece. This included 40 adults without diabetes mellitus who either had a body mass index (BMI)>30 kg/m², or a BMI of 27-29.9 kg/m² and at least one weight-related co-morbidity. The aim was to assess the association of baseline characteristics with the magnitude of weight loss and determine predictors of poor response.

Results: This real-world chart review included 28 females and12 males with a median age of 47 years old, weight of 111.7 kg and BMI of 39.7 kg/m². The median weight reduction was 6.6% and 13.3%, following 3 and 6 months of semaglutide treatment, respectively. This study showed significant heterogeneity in response to semaglutide, with nine individuals (22.5%) being non-responders, defined as achieving a weight loss <3% at 3 months or <5% at 6 months. Baseline BMI was not associated with 3-month percentage weight loss (P=0.086). Regarding the effect of gender on semaglutide-induced weight loss, the median 3-month percentage weight loss was similar: 6.9% in females and 6.4% in males (P=0.46). However, the percentage of non-responders was higher amongst males (41.6% compared to 14.2% among females, but not statistically significant; P=0.057). Patients with a history of psychiatric illness were overrepresented in the non-responders group, with 4 out of 9 patients (44.4%) not showing a favourable response. The only three individuals who experienced weight gain at 3 months were all females with active major depressive disorder.

Discussion: This retrospective study confirmed the great variability in semaglutide-related weight loss outcomes, with males having a higher likelihood of suboptimal response compared to females. The novel finding was the link of psychiatric disease, especially active depression, with poor response to semaglutide, highlighting the need to evaluate the efficacy of semaglutide in patients with active psychiatric disease. Determining the predictors of response to semaglutide is essential to facilitate personalised treatment of obesity.