Cost-Effectiveness of Highly Effective Glucose-Lowering Agents: Do Current Practices Optimize Clinical and Economic Outcomes?

INTRODUCTION: Advances in type 2 diabetes (T2D) treatment have expanded therapeutic options, but evidence on optimal treatment sequencing for long-term outcomes remains limited. This study evaluated six common T2D treatment pathways in the US using long-term modeling. METHODS: A literature review of guidelines and published data identified 495 treatment sequences across 77 studies. The six most frequently reported pathways were selected for modeling analyses using the PRIME T2D Model. Metformin was first-line therapy in all modeled pathways. Empagliflozin 10 mg (EMPA) was added as second-line therapy in four pathways, followed by either tirzepatide 10 mg (TZP), liraglutide 1.8 mg (LIRA), semaglutide 1.0 mg (SEMA) or dulaglutide 3.0 mg (DULA) as third-line therapy. In two pathways, TZP or SEMA were introduced as second-line agents, followed by EMPA as the third-line therapy. Basal and basal-bolus insulin were fourth- and fifth-line therapies in all analyses. Treatment intensification was modeled every 3 years or when glycated hemoglobin (HbA1c) exceeded 7.5%. RESULTS: When used as third-line treatment, more efficacious agents improved clinical outcomes and increased costs relative to comparators. As the most efficacious third-line therapy, TZP was associated with incremental cost-effectiveness ratios (ICERs) of $50,545, $25,563, and $8,173 per quality-adjusted life years (QALYs) gained versus LIRA, SEMA and DULA, respectively, assuming intensification every 3 years. When used as second-line therapy, more efficacious agents further improved clinical outcomes but also contributed to higher direct costs over patients' lifetimes. Second-line TZP was associated with ICERs of $59,434 per QALY gained versus second-line SEMA, when intensification at HbA1c 7.5% was applied. CONCLUSIONS: Initiating more efficacious therapies early in T2D treatment may improve long-term outcomes. Though associated with higher upfront costs, these therapies may reduce complication-related costs over time. Use of modern, efficacious therapies earlier in disease management may be a cost-effective strategy for healthcare payers.