Background: Incretin-based obesity medications (IOMs) produce substantial weight loss, but the incremental benefit of structured nutritional therapy when integrated with pharmacotherapy remains unclear. Objectives: To compare 12-month weight-loss outcomes between individualized carbohydrate-reduced nutritional therapy combined with IOMs (VINT+IOM) and IOM-based care without structured nutritional therapy (IOM only). Methods: This retrospective cohort study evaluated 4,269 adults enrolled in a comprehensive telemedicine obesity care program (VINT+IOM, n=1,658; IOM only, n=2,611). Both pathways included clinician-guided medication management and behavioral coaching. The primary analysis focused on GLP-1-naive participants receiving either semaglutide or tirzepatide without switching medications during follow-up. Adjusted weight changes were estimated using longitudinal linear mixed-effects models accounting for baseline demographic and clinical characteristics. Additional analyses evaluated weight-loss responders, prior GLP-1 exposure, and medication utilization. Results: Among GLP-1-naive semaglutide users, adjusted 12-month weight loss was greater with VINT+IOM than IOM only (30.7 vs. 24.1 lb; P=0.01), with corresponding observed weight loss of 13.3% versus 11.1%. Among tirzepatide users, adjusted weight loss was 45.9 versus 34.4 lb (P=0.003), with observed reductions of 19.7% versus 15.6%, respectively. Weight-loss responder rates consistently favored VINT+IOM. In the overall cohort, including GLP-1-naive participants, those with prior GLP-1 exposure, and participants with varying medication trajectories, adjusted weight loss was 29.4 versus 21.5 lb (P less than 0.001), with observed reductions of 12.7% versus 9.6%. Greater weight loss with VINT+IOM was also observed among participants with prior GLP-1 exposure. Weight loss continued between 6 and 12 months in both pathways. Medication coverage was high, with approximately 80% of participants achieving a proportion of days covered of at least 80% in both pathways. Conclusions: Integrating individualized carbohydrate-reduced nutritional therapy with IOM-based care was associated with greater 12-month weight loss than IOM-based care without structured nutritional therapy. These real-world findings support further evaluation of individualized nutritional approaches as an adjunct to incretin-based obesity pharmacotherapy.