{
  "abstract": "Introduction To assess the within-class variation in kidney outcomes following initiation of sulfonylurea therapy.Research design and methods We used claims data of enrollees in commercial, Medicare Advantage, and traditional Medicare health plans between 2014 and 2021 to emulate a target trial including adults ≥21 years with type 2 diabetes at moderate cardiovascular risk to compare initiation of glimepiride, glipizide, or glyburide on the incidence of chronic kidney disease (CKD) stage 3 or worse, including initiation of kidney replacement therapy (primary outcome); secondary outcomes examined incident CKD stages 3-4, kidney failure (including kidney replacement therapy), all-cause mortality, and hypoglycemia requiring emergency department or hospital care. Random treatment assignment was emulated using propensity scores, estimated using the super learner ensemble method, and incorporated as inverse probability of treatment weights into proportional hazards models.Results The weighted study cohort included 295 092 individuals starting glimepiride (n=134 926), glipizide (n=145 984), and glyburide (n=14 182). One year after treatment initiation, stage 3 or worse CKD developed in 2.1% of patients in the glimepiride group, 2.2% in the glipizide group, and 1.8% in the glyburide group. Glyburide was associated with a lower risk of kidney complications compared with both glimepiride (HR 0.84, 95% CI 0.76 to 0.92) and glipizide (HR 0.81, 95% CI 0.73 to 0.89), despite a higher risk of severe hypoglycemia (HR 1.47, 95% CI 1.27 to 1.71 vs glipizide and HR 1.22, 95% CI 1.05 to 1.42 vs glimepiride). In contrast, the risk of kidney complications was modestly increased with glipizide compared with glimepiride use (HR 1.04, 95% CI 1.00 to 1.07).Conclusions Glyburide was associated with a modestly lower risk of kidney complications, despite a higher risk of hypoglycemia, while glipizide was associated with a higher risk of kidney complications. These hypothesis-generating findings suggest important within-class differences that warrant consideration in clinical decision-making and future research. Despite rigorous prespecified causal inference analytic methods, the risk of unmeasured confounding and bias by indication with the use of observational data remains.Trial registration number NCT05214573.",
  "authors": [
    {
      "affiliations": [
        "School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA"
      ],
      "name": "Stacey Sklepinski"
    },
    {
      "affiliations": [
        "Division of Gerontology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA",
        "University of Maryland Institute for Health Computing, North Bethesda, Maryland, USA"
      ],
      "name": "Alexandria A Ratzki-Leewing"
    },
    {
      "affiliations": [
        "Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA"
      ],
      "name": "Jeph Herrin"
    },
    {
      "affiliations": [
        "Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Rochester, Minnesota, USA",
        "Optum Labs, Eden Prairie, Minnesota, USA"
      ],
      "name": "Kavya Sindhu Swarna"
    },
    {
      "affiliations": [
        "Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Rochester, Minnesota, USA",
        "Optum Labs, Eden Prairie, Minnesota, USA"
      ],
      "name": "Yihong Deng"
    },
    {
      "affiliations": [
        "Department of Public Health Sciences, The University of Chicago, Chicago, Illinois, USA"
      ],
      "name": "Eric C Polley"
    },
    {
      "affiliations": [
        "Department of Pharmacotherapy, Washington State University, Spokane, Washington, USA",
        "Providence Medical Research Center, Spokane, Washington, USA"
      ],
      "name": "Joshua J Neumiller"
    },
    {
      "affiliations": [
        "Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA"
      ],
      "name": "Rodolfo J Galindo"
    },
    {
      "affiliations": [
        "Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA"
      ],
      "name": "Guillermo E Umpierrez"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA",
        "Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, USA"
      ],
      "name": "Joseph S Ross"
    },
    {
      "affiliations": [
        "Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA",
        "Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Juan P Brito"
    },
    {
      "affiliations": [
        "Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA",
        "Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Victor M Montori"
    },
    {
      "affiliations": [
        "Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Rochester, Minnesota, USA"
      ],
      "name": "Mindy M Mickelson"
    },
    {
      "affiliations": [
        "Division of Gerontology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA",
        "University of Maryland Institute for Health Computing, North Bethesda, Maryland, USA",
        "Division of Endocrinology, Diabetes, & Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA"
      ],
      "name": "Rozalina Grubina McCoy"
    }
  ],
  "title": "Comparative effectiveness of sulfonylureas on kidney outcomes in adults with type 2 diabetes and moderate cardiovascular risk: a target trial emulation",
  "uid": "7cc07efa-b081-5baa-96e3-df004d01142d"
}