Evidence mapPaperPMID 41760122Full record

ArticleBMJ open diabetes research & care2026

Comparative safety of sulfonylurea therapies on cardiovascular and severe hypoglycemia outcomes among adults with type 2 diabetes and moderate cardiovascular risk: a target trial emulation.

Stacey Sklepinski, Alexandria A Ratzki-Leewing, Jeph Herrin, Kavya Sindhu Swarna, Yihong Deng, Eric C Polley, Joshua J Neumiller, Rodolfo J Galindo, Guillermo E Umpierrez, Joseph S Ross and 6 more

Abstract readComparative Study
In one paragraph

Article in BMJ open diabetes research & care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Stacey SklepinskiSchool of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA.ORCID http://orcid.org/0009-0009-3857-9445
Alexandria A Ratzki-LeewingUniversity of Maryland Institute for Health Computing, North Bethesda, Maryland, USA.ORCID http://orcid.org/0000-0002-9474-7900
Jeph HerrinSection of Cardiovascular Medicine, Department of Medicine, Yale University, New Haven, Connecticut, USA.
Kavya Sindhu SwarnaMayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Rochester, Minnesota, USA.
Yihong DengMayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Rochester, Minnesota, USA.
Eric C PolleyDepartment of Public Health Sciences, The University of Chicago, Chicago, Illinois, USA.
Joshua J NeumillerDepartment of Pharmacotherapy, Washington State University, Pullman, Washington, USA.
Rodolfo J GalindoDivision of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
Guillermo E UmpierrezDivision of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.ORCID http://orcid.org/0000-0002-3252-5026
Joseph S RossDepartment of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
Juan P BritoDivision of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, New York, USA.
Victor M MontoriDivision of Endocrinology, Mayo Clinic, Rochester, Minnesota, USA.ORCID http://orcid.org/0000-0003-0595-2898
Bijan J BorahMayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Rochester, Minnesota, USA.
Bradley A MaronUniversity of Maryland Institute for Health Computing, North Bethesda, Maryland, USA.
Mindy M MickelsonMayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Rochester, Minnesota, USA.
Rozalina Grubina McCoyUniversity of Maryland Institute for Health Computing, North Bethesda, Maryland, USA rozalina.mccoy@som.umaryland.edu.ORCID http://orcid.org/0000-0002-2289-3183

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionTo examine within-class sulfonylurea safety, we compared risks of major adverse cardiovascular events (MACE) and severe hypoglycemia among adults with type 2 diabetes (T2D) and moderate cardiovascular risk following sulfonylurea initiation. RESEARCH DESIGN AND

methodsWe conducted a target trial emulation including adults ≥21 years old with T2D and moderate cardiovascular risk who initiated glimepiride, glipizide or glyburide between 2014 and 2021, using claims data from Optum Labs Data Warehouse and the Medicare fee-for-service 100% sample. Study outcomes were MACE (primary), expanded MACE and its components and emergency department or hospital encounters for hypoglycemia, ascertained during follow-up through 2022. Inverse probability of treatment weighting (IPTW) was applied using propensity scores estimated using the super learner ensemble, and outcomes were examined using IPTW Cox proportional hazards models.

resultsThe weighted study cohort comprised 314 699 patients (mean age 66.9 years, 52.0% men, 76.6% non-Hispanic white). At 1 year, MACE was experienced by 2.5%, 2.7% and 2.8% of patients starting glimepiride, glipizide and glyburide, respectively. Compared with glimepiride, glyburide and glipizide were associated with higher risk of MACE (HR 1.10, 95% CI 1.05 to 1.16 for glyburide; HR 1.05, 95% CI 1.03 to 1.07 for glipizide). At 1 year, severe hypoglycemia was experienced by 0.3%, 0.3% and 0.4% of patients starting glimepiride, glipizide and glyburide, respectively. Glyburide was associated with a greater risk of severe hypoglycemia compared with glipizide (HR 1.43, 95% CI 1.23 to 1.65), while glipizide was associated with a lower risk compared with glimepiride (HR 0.82, 95% CI 0.77 to 0.87).

conclusionsAmong adults with T2D and moderate cardiovascular risk, glimepiride was associated with lowest risk of MACE and glipizide with lowest risk of severe hypoglycemia. These results can help inform treatment selection if sulfonylureas are used for glucose-lowering.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2HypoglycemiaHypoglycemic AgentsSulfonylurea CompoundsAgedFemaleFollow-Up StudiesGlipizideGlyburideHeart Disease Risk FactorsHumansInsulin SecretagoguesMaleMiddle AgedUnited StatesglimepirideGlipizideGlyburideHypoglycemic AgentsInsulin SecretagoguesSulfonylurea CompoundsCardiovascular SystemDiabetes Mellitus, Type 2GlyburideHypoglycemia

Identifiers

PMID41760122
PMCPMC12958991

What Socratic holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.