Chintan V. Dave, PharmD, PhD; Sebastian Schneeweiss, MD, ScD; Dae Kim, MD, MPH, ScD; Michael Fralick, MD, SM; Angela Tong, MS; Elisabetta Patorno, MD, DrPH
Financial Support: By the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Dr. Patorno was supported by a career development grant (K08AG055670) from the National Institute on Aging.
Disclosures: Dr. Schneeweiss reports personal fees from WHISCON and Aetion and grants from Boehringer Ingelheim, Bayer, and Vertex outside the submitted work. Dr. Kim reports grants from the National Institute on Aging and personal fees from Alosa Health outside the submitted work. Dr. Patorno was supported by a career development grant (K08AG055670) from the National Institute on Aging; she is the investigator of investigator-initiated grants to the Brigham and Women's Hospital from Boehringer Ingelheim and GSK, not directly related to the topic of the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-3136.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement: Study protocol and statistical code: Available from Dr. Patorno (e-mail, email@example.com). Data set: Available from data vendors through a data use agreement.
Corresponding Author: Chintan V. Dave, PharmD, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, 1620 Tremont Street, Suite 3030, Boston MA 02120; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Dave, Schneeweiss, Kim, Fralick, and Patorno and Ms. Tong: 1620 Tremont Street, Suite 3030, Boston, MA 02120.
Author Contributions: Conception and design: C.V. Dave, S. Schneeweiss, M. Fralick, E. Patorno.
Analysis and interpretation of the data: C.V. Dave, D. Kim, M. Fralick, E. Patorno.
Drafting of the article: C.V. Dave.
Critical revision of the article for important intellectual content: C.V. Dave, S. Schneeweiss, D. Kim, M. Fralick, E. Patorno.
Final approval of the article: C.V. Dave, S. Schneeweiss, D. Kim, M. Fralick, A. Tong, E. Patorno.
Statistical expertise: C.V. Dave, S. Schneeweiss.
Obtaining of funding: S. Schneeweiss, E. Patorno.
Administrative, technical, or logistic support: S. Schneeweiss, A. Tong, E. Patorno.
Collection and assembly of data: C.V. Dave, S. Schneeweiss, A. Tong.
Prior studies evaluating risk for severe urinary tract infections (UTIs) with sodium–glucose cotransporter-2 (SGLT-2) inhibitors have reported conflicting findings.
To assess whether patients initiating use of SGLT-2 inhibitors were at increased risk for severe UTI events compared with those initiating use of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor (GLP-1) agonists.
Population-based cohort study.
2 large, U.S.-based databases of commercial claims (March 2013 to September 2015).
Within each database, 2 cohorts were created and matched 1:1 on propensity score. Patients were aged 18 years or older, had type 2 diabetes mellitus, and were initiating use of SGLT-2 inhibitors versus DPP-4 inhibitors (cohort 1) or GLP-1 agonists (cohort 2).
The primary outcome was a severe UTI event, defined as a hospitalization for primary UTI, sepsis with UTI, or pyelonephritis; the secondary outcome was outpatient UTI treated with antibiotics. Hazard ratios (HRs) were estimated in each propensity score–matched cohort, with adjustment for more than 90 baseline characteristics.
After 1:1 matching on propensity score, 123 752 patients were identified in cohort 1 and 111 978 in cohort 2 in the 2 databases. In cohort 1, persons newly receiving SGLT-2 inhibitors had 61 severe UTI events (incidence rate [IR] per 1000 person-years, 1.76), compared with 57 events in the DPP-4 inhibitor group (IR, 1.77) (HR, 0.98 [95% CI, 0.68 to 1.41]). In cohort 2, those receiving SGLT-2 inhibitors had 73 events (IR, 2.15), compared with 87 events in the GLP-1 agonist group (IR, 2.96) (HR, 0.72 [CI, 0.53 to 0.99]). Findings were robust across sensitivity analyses; within several subgroups of age, sex, and frailty; and for canagliflozin and dapagliflozin individually. In addition, SGLT-2 inhibitors were not associated with increased risk for outpatient UTIs (cohort 1: HR, 0.96 [CI, 0.89 to 1.04]; cohort 2: HR, 0.91 [CI, 0.84 to 0.99]).
Generalizability of the study findings may be limited to patients with commercial insurance.
In a large cohort of patients seen in routine clinical practice, risk for severe and nonsevere UTI events among those initiating SGLT-2 inhibitor therapy was similar to that among patients initiating treatment with other second-line antidiabetic medications.
Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics.
Dave CV, Schneeweiss S, Kim D, et al. Sodium–Glucose Cotransporter-2 Inhibitors and the Risk for Severe Urinary Tract Infections: A Population-Based Cohort Study. Ann Intern Med. 2019;171:248–256. [Epub ahead of print 30 July 2019]. doi: 10.7326/M18-3136
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Published: Ann Intern Med. 2019;171(4):248-256.
Published at www.annals.org on 30 July 2019
Infectious Disease, Nephrology, Urinary Tract Infection, Urological Disorders.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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