Real-World Effectiveness, Safety, and Use Patterns of GLP-1 Receptor Agonists in Obesity and Type 2 Diabetes: A Nationwide Multicentre Community Pharmacy Study

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of obesity and type 2 diabetes mellitus (T2DM). Although randomized clinical trials have demonstrated substantial weight loss and metabolic benefits, real-world evidence is needed to assess their effectiveness, safety, prescribing patterns, and use in routine clinical practice. Objective: To evaluate the effectiveness and safety of GLP-1 receptor agonists in routine clinical practice and to identify factors associated with treatment outcomes in a nationwide multicenter cohort recruited through Spanish community pharmacies. Methods: A nationwide multicentre cross-sectional study with retrospective data collection was conducted between January and April 2026 across community pharmacies in Spain. Adult patients receiving GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists were consecutively enrolled and classified according to therapeutic indication (obesity or T2DM). Changes in body weight and body mass index (BMI) were assessed using paired-samples t-tests, while multivariable linear regression explored independent determinants of weight loss. Safety signals were initially evaluated using disproportionality analyses based on Odds Ratios (ORs). Subsequently, multivariable logistic regression was performed to identify independent predictors of digestive adverse drug reactions after adjustment for demographic characteristics, treatment-related variables, lifestyle factors, and concomitant glucose-lowering therapies. Results: A total of 531 patients were included (52.2% obesity; 47.8% T2DM; mean age 56.5 ± 12.5 years; 66.7% women). Patients achieved a significant mean weight loss of 12.17 ± 10.64 kg, corresponding to an 11.71% ± 9.40% reduction from baseline (p < 0.001). Overall, 73.9% and 54.1% of participants achieved ≥5% and ≥10% weight loss, respectively. Relative weight loss was comparable across incretin-based therapies. Gastrointestinal adverse drug reactions were the most frequently reported safety outcomes. Disproportionality analyses identified brand-specific safety signals, including increased reporting of nausea/vomiting with Wegovy® and constipation with Mounjaro®, whereas concomitant insulin and SGLT2 inhibitor therapy were associated with dizziness and urinary disorders, respectively. In the multivariable logistic regression model, increasing age emerged as the only independent predictor associated with a lower likelihood of digestive adverse drug reactions (adjusted OR 0.97 per year; 95% CI 0.96–0.99; p = 0.003), while no independent associations were observed for GLP-1RA agent, treatment duration, lifestyle variables, or concomitant glucose-lowering medications after adjustment. Conclusions: Incretin-based therapies were associated with clinically meaningful weight loss in routine clinical practice, supporting the generalizability of findings from randomized clinical trials. Safety profiles differed according to treatment and concomitant therapies, highlighting the importance of individualized monitoring in community pharmacy settings. These findings support the development of a standardized pharmacy-led dispensing and follow-up protocol to optimize patient safety and treatment adherence.