Glucagon-like Peptide-1 Receptor Agonists in the Real World: Are Clinical Trials Reproducible? A Spanish Pilot Study

Introduction: Obesity is a chronic, multifactorial disease associated with significant metabolic and cardiovascular complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective pharmacological options for weight management, demonstrating clinically relevant weight loss in controlled trials. However, real-world evidence is essential to assess their effectiveness and safety under routine clinical conditions and to verify if trial results are reproducible in diverse populations. Objective: We aimed to evaluate the effectiveness and safety of GLP-1RAs in terms of weight loss in real-world clinical practice and to compare outcomes among different available agents, focusing on their impact on obesity management. Method: A cross-sectional, observational pilot study was conducted in Spain. Adult patients receiving GLP-1RAs for at least four weeks were included. Data collected included sociodemographic variables, treatment characteristics, anthropometric measurements, and adverse effects. Weight loss outcomes were analyzed using descriptive statistics, ANOVA for inter-drug comparisons, and multivariate ANCOVA to adjust for confounders. This pilot study also validated the protocol for a subsequent nationwide multicenter study. Results: A total of 32 patients (62.5% women; mean age 58.2 years) were analyzed. Mean weight loss was 2.97 kg (3.17%). Significant differences between drugs were observed (p = 0.005), with semaglutide 2.4 mg (Wegovy^®) showing the greatest weight reduction (11.0 kg). Patients without diabetes achieved significantly greater weight loss than those with diabetes (5.0 vs. 0.8 kg; p = 0.021). Treatments were well tolerated, with 53.1% reporting no adverse effects; most side effects were mild gastrointestinal symptoms. Conclusions: GLP-1RAs are effective and well-tolerated for obesity treatment in real-world clinical practice, although weight loss is more modest than in pivotal clinical trials. Differences between agents were observed after multivariate adjustment, although these findings should be interpreted cautiously given the exploratory pilot design and limited sample size. These findings support the need for individualized treatment strategies in obesity care. This pilot study successfully validated the methodology for an ongoing nationwide investigation.