OBJECTIVES: To evaluate the cost-effectiveness of sulfonylurea (SU), thiazolidinedione (TZD), dipeptidyl peptidase 4 inhibitors (DPP-4i), and sodium-glucose co-transporter-2 inhibitors (SGLT2i) as long-term add-on therapy with metformin for type 2 diabetes mellitus (T2DM) in US health care payer perspective and assess the effect of medication adherence on therapeutic effectiveness.

METHODS: The estimation of direct medical cost and quality-adjusted life years (QALYs) in 25-year time horizon was performed by using a one-year cycle Markov model with four health states. Cohorts, aged 60 years old, were treated with dual therapy when first-line metformin monotherapy failed. It then a triple therapy with insulin was given after the failure of dual therapy. Additionally, TZD were replaced with SGLT2i if heart failure occurs as a complication. Adherence to therapies were considered as weighting parameters of probabilities for treatment failure and diabetes complications. Costs, clinical outcomes, and utilities were retrieved from literature. Cost and effectiveness were discounted at 3% in 2020 value.

RESULTS: In scenario A (without considering medication adherence), DPP-4i increased 0.18 QALYs with incremental cost $13,842 compared to TZD, resulting in an ICER of $74,911 per QALY. In scenario B (considering medication adherence), DPP-4i increased 0.09 QALYs with incremental cost $5,073 compared to TZD, resulting in an ICER of $53,610 per QALY. The cost-effectiveness acceptability curves indicated that TZD gained highest probability as the most cost-effective strategy at willingness-to-pay (WTP) threshold $50,000 per QALY in both scenario A and B. Moreover, SGLT2i was the most cost-effective strategy at the threshold of $140,000 in scenario B.

CONCLUSIONS: TZD was the most cost-effective alternative whether considering medication adherence or not. Although Dpp-4i and SGLT2i gained additional QALYs, compared to TZD, the benefit could not outweigh the tremendous health related expenditure. Our study will be valuable both for third-party payers and clinicians to make decisions in second-line T2DM therapies.