Preadmission GLP-1 Receptor Agonist Plus SGLT2 Inhibitor Use and Early Outcomes After Pneumonia Hospitalization in Adults With Type 2 Diabetes

Official title

Preadmission GLP-1 Receptor Agonist Plus SGLT2 Inhibitor Use and Early Outcomes After Pneumonia Hospitalization in Adults With Type 2 Diabetes: A Target Trial Emulation

Overview

This retrospective observational target-trial emulation uses electronic health record data from the TriNetX US Collaborative Network to compare preadmission glucose-lowering treatment strategies in adults with type 2 diabetes hospitalized with pneumonia. Time zero is the date of the index pneumonia admission. The study compares patients with evidence of prescriptions for both a GLP-1 receptor agonist and an SGLT2 inhibitor in the year before admission with patients prescribed a GLP-1 receptor agonist alone, an SGLT2 inhibitor alone, or usual care. Usual care includes metformin, sulfonylureas, or DPP-4 inhibitors without either study class. The primary outcome is a composite of all-cause death, invasive mechanical ventilation, or renal replacement therapy within 30 days of admission, with the individual components and 12-month mortality, major adverse cardiovascular events, and major adverse kidney events also evaluated. Propensity-score methods are used to reduce bias from nonrandom treatment selection.

Primary outcome measures

• Composite outcome (all-cause mortality, invasive mechanical ventilation, or renal replacement therapy) [Time frame: Within 30 days after the index pneumonia admission]

Secondary outcome measures (7)

• All-cause mortality [Time frame: Within 30 days after the index pneumonia admission]
• Invasive mechanical ventilation [Time frame: Within 30 days after the index pneumonia admission]
• Renal replacement therapy [Time frame: Within 30 days after the index pneumonia admission]
• Composite outcome (all-cause mortality, major adverse cardiovascular events, or major adverse kidney events) [Time frame: Through 12 months after the index pneumonia admission]
• All-cause mortality [Time frame: Through 12 months after the index pneumonia admission]
• Major adverse cardiovascular events [Time frame: Through 12 months after the index pneumonia admission]
• Major adverse kidney events [Time frame: Through 12 months after the index pneumonia admission]

Eligibility criteria

Inclusion criteria

• Adults aged 18 years or older.
• Type 2 diabetes mellitus
• Hospitalization with pneumonia during the study period, serving as the index admission
• Prescription of a GLP-1 receptor agonist, an SGLT2 inhibitor, or usual-care glucose-lowering therapy in the year before the index admission
• No GLP-1 receptor agonist or SGLT2 inhibitor prescription in the 6 months before the first qualifying prescription

Exclusion criteria

• Type 1 diabetes mellitus, or other specified diabetes types that are not type 2 diabetes
• Human immunodeficiency virus infection
• Bariatric surgery
• Solid-organ transplantation
• Pneumonia hospitalization, invasive mechanical ventilation, or renal replacement therapy in the year before the index admission
• End-stage kidney disease, dialysis dependence, ventilator dependence, or tracheostomy status
• Metastatic malignancy, lung cancer, or palliative care
• Viral pneumonia, influenza with pneumonia, or COVID-19 around the index admission
• Acute cardiovascular event in the 6 months before the index admission

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Taiwan · 1 center

• Chung Shan Medical University Hospital — Taichung

Publications

• Simms-Williams N, Treves N, Yin H, Lu S, Yu O, Pradhan R, Renoux C, Suissa S, Azoulay L. Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study. BMJ. 2024 Apr 25;385:e078242. doi: 10.1136/bmj-2023-078242. PMID 38663919
• Wright AK, Carr MJ, Kontopantelis E, Leelarathna L, Thabit H, Emsley R, Buchan I, Mamas MA, van Staa TP, Sattar N, Ashcroft DM, Rutter MK. Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes. Diabetes Care. 2022 Apr 1;45(4):909-918. doi: 10.2337/dc21-1113. PMID 35100355
• Palchuk MB, London JW, Perez-Rey D, Drebert ZJ, Winer-Jones JP, Thompson CN, Esposito J, Claerhout B. A global federated real-world data and analytics platform for research. JAMIA Open. 2023 May 13;6(2):ooad035. doi: 10.1093/jamiaopen/ooad035. eCollection 2023 Jul. PMID 37193038
• Topaloglu U, Palchuk MB. Using a Federated Network of Real-World Data to Optimize Clinical Trials Operations. JCO Clin Cancer Inform. 2018 Dec;2:1-10. doi: 10.1200/CCI.17.00067. PMID 30652541
• VanderWeele TJ, Ding P. Sensitivity Analysis in Observational Research: Introducing the E-Value. Ann Intern Med. 2017 Aug 15;167(4):268-274. doi: 10.7326/M16-2607. Epub 2017 Jul 11. PMID 28693043
• Lipsitch M, Tchetgen Tchetgen E, Cohen T. Negative controls: a tool for detecting confounding and bias in observational studies. Epidemiology. 2010 May;21(3):383-8. doi: 10.1097/EDE.0b013e3181d61eeb. PMID 20335814
• Austin PC, Lee DS, Fine JP. Introduction to the Analysis of Survival Data in the Presence of Competing Risks. Circulation. 2016 Feb 9;133(6):601-9. doi: 10.1161/CIRCULATIONAHA.115.017719. PMID 26858290
• Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011 May;46(3):399-424. doi: 10.1080/00273171.2011.568786. Epub 2011 Jun 8. PMID 21818162

Identifiers

NCT: NCT07708610 · CS2-26152

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗