Cost-Effectiveness of Semaglutide vs. Empagliflozin, Canagliflozin, and Sitagliptin for Treatment of Patients with Type 2 Diabetes in Denmark: A Decision-Analytic Modelling Study

OBJECTIVE: The aim was to evaluate the cost-effectiveness of oral and subcutaneous semaglutide versus other oral glucose-lowering drugs (i.e., empagliflozin, canagliflozin, and sitagliptin) for the management of type 2 diabetes (T2D) in Denmark using clinically relevant treatment intensification rules. METHODS: A Markov-type cohort model for evaluating the cost-effectiveness of treatment pathways for T2D was used to produce cost-effectiveness estimates based on four head-to-head trials. Evidence from PIONEER 2 and 3 trials was used to evaluate the cost-effectiveness of oral semaglutide vs. empagliflozin and sitagliptin. Evidence from SUSTAIN 2 and 8 trials was used to evaluate the cost-effectiveness of subcutaneous semaglutide vs. sitagliptin and canagliflozin. Base case analyses used trial product estimands of treatment efficacy to avoid the confounding effects of rescue medication use during trials. Deterministic scenario analyses and probabilistic sensitivity analyses were conducted to assess robustness of cost-effectiveness estimates. RESULTS: Semaglutide-based treatment regimens were consistently associated with higher lifetime diabetes treatment costs, lower costs of complications, and higher lifetime accumulated QALYs. The PIONEER 2 analysis estimated the cost-effectiveness of oral semaglutide vs. empagliflozin was DKK 150,618/QALY (€20,189). The PIONEER 3 analysis estimated the cost-effectiveness of oral semaglutide vs. sitagliptin was DKK 95,093/QALY (€12,746). The SUSTAIN 2 analysis estimated the cost-effectiveness of subcutaneous semaglutide vs. sitagliptin was DKK 79,982/QALY (€10,721). The SUSTAIN 8 analysis estimated the cost-effectiveness of subcutaneous semaglutide vs. canagliflozin was DKK 167,664/QALY (€22,474). CONCLUSIONS: Daily oral and weekly subcutaneous semaglutide are likely to both increase cost and health benefits, but are likely to do so under commonly considered cost-effectiveness thresholds. TRIAL REGISTRATIONS: Clinicaltrials.gov: NCT02863328 (PIONEER 2; registered August 11, 2016); NCT02607865 (PIONEER 3; registered November 18, 2015); NCT01930188 (SUSTAIN 2; registered August 28, 2013); NCT03136484 (SUSTAIN 8; registered May 2, 2017). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41669-023-00416-z.