HoJin Shin1, Sebastian Schneeweiss1,2, Robert J Glynn1, Elisabetta Patorno1. 1. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. 2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Abstract
PURPOSE: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are increasingly being considered as first-line treatment for type 2 diabetes (T2D). The benefits of SGLT-2i from cardiovascular outcome trials may lead to preferential prescribing of SGLT-2i to patients at high cardiovascular risk, possibly causing confounding in non-randomized studies of SGLT-2i as first-line treatment. We assessed evolving imbalances in characteristics of patients starting SGLT-2i versus metformin as first-line monotherapy. METHODS: Using claims data from two US commercial health insurance and Medicare, we identified patients with T2D aged ≥18 years (>65 years in Medicare) initiating first-line SGLT-2i or metformin from 2013 through 2019. Standardized differences (SDs) for patient characteristics were assessed during four consecutive calendar time blocks (T1:4/2013-12/2014; T2:1/2015-6/2016; T3:7/2016-12/2017; and T4:1/2018-12/2019). We also estimated the propensity score of receiving SGLT-2i versus metformin within each time block and evaluated time trends in model discrimination with c-statistics. RESULTS: We identified 9113 initiators of first-line SGLT-2i and 810 348 initiators of first-line metformin. During T1, SGLT-2i initiators were younger (SD = -0.24) and less likely to have seen cardiologists (-0.07) with a similar prevalence of CVD (0.04) compared with metformin. During T4, patients were more balanced for age (-0.01). Cardiologist visits (0.08) and CVD (0.25) became more prevalent among SGLT-2i initiators. CONCLUSIONS: When comparing initiators of first-line SGLT-2i versus metformin, imbalances in patient characteristics evolved from 2013 through 2019, particularly channeling SGLT-2i to individuals at high cardiovascular risk. Evolving channeling in prescribing first-line SGLT-2i should be expected and accounted for in non-randomized comparative effectiveness research.
PURPOSE: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are increasingly being considered as first-line treatment for type 2 diabetes (T2D). The benefits of SGLT-2i from cardiovascular outcome trials may lead to preferential prescribing of SGLT-2i to patients at high cardiovascular risk, possibly causing confounding in non-randomized studies of SGLT-2i as first-line treatment. We assessed evolving imbalances in characteristics of patients starting SGLT-2i versus metformin as first-line monotherapy. METHODS: Using claims data from two US commercial health insurance and Medicare, we identified patients with T2D aged ≥18 years (>65 years in Medicare) initiating first-line SGLT-2i or metformin from 2013 through 2019. Standardized differences (SDs) for patient characteristics were assessed during four consecutive calendar time blocks (T1:4/2013-12/2014; T2:1/2015-6/2016; T3:7/2016-12/2017; and T4:1/2018-12/2019). We also estimated the propensity score of receiving SGLT-2i versus metformin within each time block and evaluated time trends in model discrimination with c-statistics. RESULTS: We identified 9113 initiators of first-line SGLT-2i and 810 348 initiators of first-line metformin. During T1, SGLT-2i initiators were younger (SD = -0.24) and less likely to have seen cardiologists (-0.07) with a similar prevalence of CVD (0.04) compared with metformin. During T4, patients were more balanced for age (-0.01). Cardiologist visits (0.08) and CVD (0.25) became more prevalent among SGLT-2i initiators. CONCLUSIONS: When comparing initiators of first-line SGLT-2i versus metformin, imbalances in patient characteristics evolved from 2013 through 2019, particularly channeling SGLT-2i to individuals at high cardiovascular risk. Evolving channeling in prescribing first-line SGLT-2i should be expected and accounted for in non-randomized comparative effectiveness research.
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