Patients with type 2 diabetes starting treatment with sodium-glucose cotransporter-2 (SGLT-2) inhibitors have no greater risk for urinary tract infection (UTI) than those initiating other second-line antidiabetic medications, according to new study results published in the Annals of Internal Medicine.

Using 2 large commercial insurance databases (IBM MarketScan and Optum Clinformatics Data Mart), Chintan Dave, PharmD, PhD, of Brigham and Women’s Hospital in Boston, and colleagues examined the association between 3 classes of antidiabetics drugs—SGLT-2 inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 receptor (GLP-1) agonists—and UTI risk.

Cohort 1 comprised 123,752 propensity-score-matched patients initiating an SGLT-2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) or a DPP-4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin). Cohort 2 included 111,978 matched patients initiating an SGLT-2 inhibitor or a GLP-1 agonist (albiglutide, dulaglutide, exenatide, or liraglutide).

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In cohort 1, severe UTI occurred in 61 SGLT-2 inhibitor users (1.76 per 1000 person-years) vs 57 DPP-4 inhibitor users (1.77 per 1000 person-years) – a nominal difference. Likewise, in cohort 2, severe UTI developed in 73 SGLT-2 inhibitor users (2.15 per 1000 person-years) vs 87 GLP-1 agonist users (2.96 per 1000 person-years).

The investigators defined severe UTI as hospitalization for primary UTI, sepsis with UTI, or pyelonephritis. Despite previous concerns over dapagliflozin, molecule-specific analyses showed no differences between canagliflozin and dapagliflozin compared with DPP-4 inhibitors or GLP-1 receptor agonists. They found no differences by age, sex, or frailty. SGLT-2 inhibitors also did not increase risk for outpatient UTIs.

In 2015, the FDA revised SGLT-2 inhibitor labels to include a warning about serious UTIs based on 19 adverse reports. But several subsequent studies have found no increased risks.

“In this large population-based cohort study of patients with type 2 diabetes mellitus, SGLT-2 inhibitor use was not associated with an increase in risk for serious—or nonserious—UTIs,” Dr Dave and his collaborators wrote. The investigators suggested future studies in specific populations, such as older adults who may be particularly susceptible to severe UTI. Patients with renal insufficiency, high risk for UTI, or history of UTI, were excluded from this study and also warrant further research. In addition, these study results were limited to patients with employer-based insurance.

In an accompanying editorial, Kristian B. Filion, PhD, and Oriana H. Yu, MD, MSc, of McGill University and Lady Davis Institute of the Jewish General Hospital in Montreal, cited the study as a key addition to the literature: “Ultimately, although some uncertainty remains, the study by Dave and colleagues provides encouraging evidence of the real-world safety of SGLT-2 inhibitors, allowing patients to benefit from their use with greater confidence in their safety with respect to severe UTI.”

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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. doi:10.7326/M18-3136

Filion KB and Yu OH. Sodium–glucose cotransporter-2 inhibitors and severe urinary tract infections: Reassuring real-world evidence. Ann Intern Med. doi:10.7326/M19-1950