From the Guidelines
SGLT-2 inhibitors should be temporarily discontinued in patients diagnosed with a urinary tract infection (UTI) until the infection resolves completely and antibiotic treatment is finished, as recommended by the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1. This approach is supported by the fact that SGLT-2 inhibitors increase glucose excretion in the urine, which can potentially worsen existing UTIs by providing glucose that bacteria can use for growth. Additionally, these medications may mask symptoms of worsening infection by increasing urinary frequency, which is already a symptom of UTI. Key considerations for managing UTIs in patients taking SGLT-2 inhibitors include:
- Prompt evaluation and treatment of UTI symptoms, such as burning with urination, frequency, urgency, cloudy urine, or fever
- Temporary discontinuation of SGLT-2 inhibitors in settings of reduced oral intake or fluid losses, as well as in patients with acute kidney injury or impairment in renal function 1
- Assessment of patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level 1
- Awareness of the rare but serious risk of necrotizing fasciitis of the perineum (Fournier’s gangrene) in patients taking SGLT-2 inhibitors, and prompt evaluation of patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise 1 It is essential to weigh the benefits of SGLT-2 inhibitors in reducing cardiovascular risk and improving glycemic control against the potential risks and complications associated with UTIs, and to individualize treatment decisions based on patient-specific factors and clinical judgment.
From the Research
SGLT-2 Inhibitors and UTI Risk
- The relationship between SGLT-2 inhibitors and the risk of urinary tract infections (UTIs) has been investigated in several studies 2, 3, 4, 5, 6.
- A 2022 observational study found that SGLT-2 inhibitors may increase the risk of UTI and pyelonephritis, particularly when used in combination with other antidiabetic, antidyslipidemic, or antihypertensive drugs 2.
- A case report from 2023 highlighted the importance of maintaining a high index of clinical suspicion for UTIs in patients with type 2 diabetes mellitus (T2DM) taking SGLT-2 inhibitors, such as empagliflozin, to avoid progression to life-threatening conditions 3.
- A retrospective cohort study from 2022 found that SGLT-2 inhibitors were associated with a higher risk of genital and urinary tract infections compared to dipeptidyl peptidase-4 inhibitors, sulfonylurea, and thiazolidinedione 4.
Study Findings
- A systematic review and meta-analysis of randomized controlled trials from 2018 found that SGLT-2 inhibitors increased the risk of genital infections, but the risk of UTI was not increased overall, although higher doses of dapagliflozin were associated with an increased risk 5.
- A propensity score-matched population-based cohort study from 2022 found that SGLT-2 inhibitor use was not associated with a higher risk of UTI compared to other antidiabetic agents, including dipeptidylpeptidase-4 inhibitors, sulfonylureas, glucagon-like peptide-1 receptor agonists, thiazolidinediones, and insulin 6.
Clinical Implications
- The findings of these studies suggest that SGLT-2 inhibitors may be associated with an increased risk of UTIs, particularly when used in combination with other medications or in certain patient populations 2, 3, 4.
- However, other studies have found no significant association between SGLT-2 inhibitor use and the risk of UTIs 5, 6.
- Clinicians should be aware of the potential risks and benefits of SGLT-2 inhibitors and monitor patients for signs and symptoms of UTIs, particularly when initiating or adjusting therapy 2, 3, 4, 5, 6.