medwireNews: The risk for severe urinary tract infections (UTIs) among people with type 2 diabetes in the real-world setting may be no greater with use of sodium-glucose cotransporter (SGLT)2 inhibitors than with other modern antidiabetes medications, research suggests.
In a study based on US insurance data, the medication class did not confer an increase in risk for the primary endpoint of hospitalization for primary UTI, sepsis with UTI, or pyelonephritis relative to dipeptidyl peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogs.
Chintan Dave (Brigham and Women's Hospital, Boston, Massachusetts, USA) and co-researchers found an incidence rate for the primary endpoint of 1.76 versus 1.77 per 1000 person–years among 61,876 users of SGLT2 inhibitors and an equal number of DPP-4 inhibitor users, respectively, matched on their propensity to receive an SGLT2 inhibitor.
And they found rates of 2.15 versus 2.96 per 1000 person–years among 55,989 SGLT2 inhibitor users and an equal number of matched GLP-1 analog users, respectively.
The hazard ratios for the primary outcome with SGLT2 inhibitor use were 0.98 versus DPP-4 inhibitor use and 0.72 versus GLP-1 analog use, with the latter being statistically significant for a protective effect of SGLT2 inhibitors.
The hazard ratios for the individual components of the primary endpoint followed a similar trend, and those for outpatient UTI treatment were 0.96 and 0.91 for use of SGLT2 inhibitors versus DPP-4 inhibitors and GLP-1 analogs, respectively.
In an editorial accompanying the study in the Annals of Internal Medicine, Kristian Filion and Oriana Yu, both from McGill University and Lady Davis Institute of the Jewish General Hospital in Montreal, Quebec, Canada, note that “despite use of rigorous methods, residual confounding remains possible and probably explains the unexpected protective effects observed in comparisons with GLP-1 receptor agonists.”
They describe the findings as “reassuring,” but caution that this “comes with some caveats,” most notably that the researchers excluded patients at high risk for UTIs and those with a history of the condition. This not only affects generalizability but also “prevented subgroup analyses among patients at greatest risk for the outcome of interest,” say the editorialists.
Nevertheless, they conclude the study “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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Ann Intern Med 2019; doi:10.7326/M18-3136
Ann Intern Med 2019; doi:10.7326/M19-1950