Real-world Impact of GLP-1 Receptor Agonists on Health-related Quality of Life in Type 2 Diabetes and Obesity (SEVERAL Study)

PURPOSE: To evaluate the real-world impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on health-related quality of life (HRQoL) and metabolic outcomes in adults with type 2 diabetes and obesity. METHODS: We conducted a multicenter prospective cohort study across 13 primary-care centers in Spain. Adults with type 2 diabetes and body mass index (BMI) > 30 kg/m² initiating a GLP-1 RA were followed for 44 weeks. Baseline and week-44 assessments included anthropometric and biochemical parameters and HRQoL measured using the EQ-5D index and visual analogue scale (VAS), and the SF-12 physical and mental component summaries (PCS/MCS). Changes were analyzed using paired statistical tests overall and by achievement of ≥5% weight loss. FINDINGS: Among 135 patients, significant improvements were observed in glucose, HbA1c, LDL-C, waist circumference, body weight, and BMI. HRQoL improved in EQ-5D domains including mobility, pain/discomfort, and anxiety/depression. The EQ-5D index increased from 0.71 to 0.79 (P < 0.001), and VAS from 58.3 to 65.3 (P = 0.007). SF-12 PCS improved significantly, whereas MCS showed no overall change. Patients achieving ≥5% weight loss experienced greater improvements in EQ-5D index, VAS, and PCS. Subcutaneous and oral semaglutide improved the EQ-5D index; oral semaglutide improved VAS and MCS; and subcutaneous semaglutide improved PCS. IMPLICATIONS: In routine clinical practice, GLP-1 RAs were associated with clinically meaningful improvements in HRQoL and metabolic outcomes, particularly when ≥5% weight loss is achieved, supporting the integration of patient-reported outcomes into diabetes and obesity management. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT05136287.