Abstract
Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) use has rapidly expanded across multiple chronic disease states, resulting in substantial growth in pharmacy spending. Although these agents demonstrate strong clinical benefit in clinical trials, real-world adherence and persistence remain suboptimal, raising questions about their financial value to payers.This viewpoint examines return on investment (ROI) associated with real-world use of SGLT2is and GLP-1RAs, alone and in combination, within a regional managed care organization. Review of claims and electronic health record data from more than 29,000 treatment-naive members revealed negative short-term ROI across treatment groups, driven primarily by high pharmacy costs and compounded by low adherence and persistence. Although adherent members generally experienced less growth in acute care use compared with nonadherent members, these trends were insufficient to offset medication costs within an 18-month time horizon.These findings highlight the limitations of using short-term ROI as a proxy for clinical value in high-cost chronic therapies. Negative ROI in this setting does not directly correlate to low therapeutic benefit but rather reflects delayed time to benefit, high baseline medical risk, and real-world medication use patterns. Payers may benefit from reassessing success metrics and pairing access to these therapies with targeted adherence and use management strategies to better align financial expectations with long-term value.