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No urinary tract infection risk with most SGLT2 inhibitors
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SGLT2 inhibitors do not increase the risk for urinary tract infections in people with type 2 diabetes; however, high doses of dapagliflozin may be an exception, according to findings published in CMAJ Open.
“There is a popular misconception that SGLT2 inhibitors cause urinary tract infections, especially since they clearly cause more genital infections,” Jennifer Donnan, BScPharm, MSc, a doctoral student at the Memorial University of Newfoundland School of Pharmacy in Canada, told Endocrine Today. “This study contributes to the growing body of evidence that shows that SGLT2 inhibitors are likely not causing urinary tract infections, but rather the increased urinary glucose concentration may be somehow linked to infection severity.”
Donnan and colleagues conducted a systematic review and meta-analysis of 105 randomized controlled trials focused on eight SGLT2 inhibitors, including dapagliflozin (Farxiga, Astra Zeneca), empagliflozin (Jardiance, Boehringer Ingelheim), canagliflozin (Invokana, Janssen), ipragliflozin, luseogliflozin, remogliflozin, tofogliflozin and ertugliflozin (Steglatro, Merck). All trials were required to compare the inhibitor to either placebo, no treatment or an active antidiabetic control. Doses were categorized as either high or low.
Following the literature search and review, the researchers found that there was a nonsignificant difference in urinary tract infection risk for people taking any of the eight SGLT2 inhibitors, with a few exceptions. Doses of 10 or more milligrams of dapagliflozin was associated with higher odds for urinary tract infections compared with placebo (OR = 1.3; 95% CI, 1.09-1.57), active comparators (OR = 1.44; 95% CI, 1.15-1.79) and both low (OR = 1.3; 95% CI, 1.04-1.6) and high (OR = 1.39; 95% CI, 1.12-1.72) doses of ertugliflozin. Further, canagliflozin was associated with an increase in urinary tract infection risk when taken in low doses (OR = 1.29; 95% CI, 1.03-1.64). While these exceptions were present, the researchers did note that there was no significant difference between any SGLT2 inhibitor, including dapagliflozin, when only considering trials that were considered at low risk for bias.
“We need to keep the big picture in mind here and look at all the possible benefits and harms of SGLT2 inhibitors,” Donnan said. “There is growing evidence to support the use of SGLT2 inhibitors as preferred second line agents, especially [in] those with existing cardiovascular disease. Therefore, practically speaking, the knowledge of increased rates of genital infections, and the possibility of progression of urinary tract infections to more serious infections, highlights the need to provide additional education to patients who use these agents on prevention measures to help mitigate these risks.” – by Phil Neuffer
Disclosures: The authors report no relevant financial disclosures.
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