Effectiveness of Tirzepatide and Semaglutide Within a Hybrid Care Model with Exploratory Dose–Response Analyses: A Real-World Evidence Study

Introduction: Obesity is a growing global challenge with rising prevalence and incidence rates associated with economic burdens. Despite the presence of a variety of approaches to managing obesity, care remains fragmented, and the transparency of care methodologies used by obesity providers remains limited. Hybrid models of care, which blend both digital tools and in-clinic visits, offer a promising and patient-centered approach. However, the lack of outcome-reporting standards remains a limitation. This study evaluates the effectiveness of Semaglutide and Tirzepatide in managing obesity using the newly developed International Consortium for Health Outcomes Measurement (ICHOM) Obesity standard set. Methods: This study employed a retrospective study design including 528 adults enrolled in a 6-month hybrid care model (meta[bolic], Zone.Health), to manage obesity. Participants were prescribed either a glucagon-like peptide (GLP)-1 receptor agonist (Semaglutide) or dual GLP-1/GIP receptor agonist (Tirzepatide) as part of the program alongside behavioral monitoring and virtual engagement. Outcomes were collected based on the ICHOM Obesity standard set from medical records at baseline, 3 months, and 6 months, and were analyzed using mixed for repeated measures. Subgroup analyses based on dosage bands were done using the Kruskal-Wallis test. Results: Both groups demonstrated significant improvements in weight, body mass index, waist circumference, fat mass, and glycemic control. However, within 6 months, on average, the Tirzepatide group had a greater reduction in weight (13.15 kg), waist circumference (11.34 cm), and HbA1c (0.33%) when compared with the Semaglutide group, with average reductions as 9.54 kg, 7.24 cm, and 0.23%, respectively. In the context of Tirzepatide dosage, all three groups (2.5–5 mg, 5–7.5 mg, and 7.5–15 mg) experienced significant weight loss. Conclusion: This study is among the first to apply the ICHOM Obesity Standard Set to evaluate Semaglutide and Tirzepatide in managing obesity within a hybrid care model. Tirzepatide was associated with superior clinical outcomes when compared with Semaglutide. The integration of standardized outcome reporting enhances transparency and comparability of hybrid interventions. Future studies should explore cost-effectiveness and long-term outcomes to support broader adoption.