Patients with type 2 diabetes (T2D) exhibit significantly lower semaglutide exposure compared with non-diabetic individuals at approved maintenance doses. This study aimed to quantitatively evaluate current semaglutide dosing regimens in T2D and establish an optimized maintenance dose and missed-dose recovery strategies using a population pharmacokinetic (PK) simulation approach. We evaluated steady-state average concentration (C_avg) across body weight and renal function subgroups to achieve the target concentration (40 nmol/L), required for 5% weight loss. In addition, target recovery timelines following various missed-dose scenarios were quantified. Under the current dosing regimen, the highest-weight group exhibited the lowest C_avg, failing to achieve target exposure across all renal function strata. Renal impairment increased exposure by 3–13%, indicating that body weight was the dominant determinant of exposure. Model-based simulations identified 2.9 mg as a new maintenance dose predicted to achieve target exposure across the subgroups. Furthermore, two or more consecutive missed doses requiring restarted titration delayed recovery by 42 days or more in patients with T2D. In conclusion, these findings suggest 2.9 mg as an optimized maintenance dose achieving the efficacious concentration for 5% weight loss in patients with T2D, and provide quantitative benchmarks for exposure recovery under the missed-dose scenarios in patients with T2D.