Discussion
In this nationally representative study, frequent urinary incontinence was common among adults aged ≥55 years with type 2 diabetes who met guideline indications for SGLT2is. As expected, the prevalence of urinary incontinence was much higher among women than men, affecting nearly 50% of women and almost 20% of men with guideline indications for SGLT2is specifically.
Our study highlights the large number of US adults with diabetes who are at risk of worsening urinary incontinence symptoms when initiating SGLT2is. A recent study found that SGLT2i use was associated with increased referrals to urologic care, symptoms of urinary frequency, urinary incontinence, urinary urgency, and prescription for lower urinary tract symptom management.10 Of note, the association of SGLT2i use with urinary outcomes was stronger in adults with HbA1c ≥7% compared with <7%, suggesting that people with more chronic hyperglycemia may be more prone to adverse urinary symptoms from glycosuria.10
Our study also highlights the need for future studies to understand how pre-existing urinary incontinence could affect risk of urogenital infections when initiating SGLT2is. In the general population, SGLT2is increase the risk of genital infections by threefold to fourfold (most commonly vulvovaginal candidiasis infections in women and balanitis in men).15 18–20 It is plausible that SGLT2is may be associated with a significantly higher risk of urogenital infections in the presence of frequent urinary incontinence, given that leakage of urine with high glucose concentrations provides an ideal substrate for bacterial and fungal growth. However, few studies of SGLT2is have collected data on urinary incontinence, precluding examination of this important question. One Australian study of about 1000 patients initiating dapagliflozin found only a 1.3% prevalence of urinary incontinence and no association with genital fungal infections.21 Additional studies are needed, especially since urogenital infections are the leading reason for discontinuing SGLT2is among older adults.14 15
Although evidence of increased risk of urinary tract infections (UTIs) with SGLT2i use has been mixed,22 23 it is important to clarify this association in older adults, who are more likely to develop complicated infections.24 A recent study of nursing home residents initiating SGLT2is found that approximately 10% were hospitalized for a UTI within 6 months.25 In general, older women are more likely to have recurrent UTIs with potential complications of pyelonephritis and urosepsis,26–28 while older men with pre-existing prostate issues have greater risk of UTIs and prostatitis, resulting in urinary catheterization.29 Further research is needed to understand how urinary incontinence may interact with possible UTI risk with SGLT2is.
Our study also highlights the importance of potential sex differences in SGLT2i use and adverse events. Given the nearly two-times higher prevalence of urinary incontinence in women compared with men, it is likely that women will suffer more of the adverse urinary effects from SGLT2is. Indeed, in the Korean adverse event reporting system, women were overwhelmingly more likely to report urinary events compared with men.30 Additionally, female genitalia are more susceptible to infection,20 and vulvovaginal mycotic infections are common in women taking SGLT2is.11 Women may also be more likely to use urinary pads for their incontinence, and pads substantially increase the risk of urogenital infections; a recent opinion piece stated that people using pads for urinary incontinence should not receive SGLT2is.31 Lower rates of SGLT2i prescribing for women and older adults have been reported in several studies;32–35 it is unclear what factors are driving differential rates of prescribing by sex and age. Attention is needed to understand how the higher prevalence of incontinence among women impacts their SGLT2i use and whether differential use of SGLT2is by sex affects pre-existing cardiovascular sex disparities in type 2 diabetes.36
There is a clear need for better guidance on how to counsel patients when initiating SGLT2is.37 Some experts recommend querying about urinary symptoms, particularly those over age 75 years.31 Our research suggests that women of all ages commonly have urinary incontinence, with over a third of women with diabetes aged 55–69 years experiencing frequent urinary incontinence, suggesting that clinicians may want to inquire about urinary symptoms for all women and not just those over age 75 years. Patients should be advised about the temporary expected increase in urine volume when starting SGLT2is and how it may worsen any pre-existing urinary incontinence. Another practical consideration is that the recent shortage of GLP-1RAs38 may push people towards initiating SGLT2is despite concerns about urinary side effects.
Our study has several limitations. First, we only examined indications for SGLT2is and not actual prescription data in NHANES due to low uptake during our study period (2013–2020). Second, NHANES does not ask participants about use of urinary pads or diapers for incontinence, which is a risk factor for urogenital infections. Third, we were unable to ascertain the effects of SGLT2i use on urinary incontinence, since only 43 participants (2.5%) used SGLT2is. The major strength of this study was the use of nationally representative data with detailed clinical characteristics and self-reported data that enabled the study of urinary incontinence among adults with type 2 diabetes who meet guideline indications for SGLT2is.
In conclusion, our study found a high prevalence of frequent urinary incontinence in all women and older men. While the presence of urinary incontinence should not necessarily lead to avoidance or de-prescribing of SGLT2is, incontinence should trigger increased caution and active monitoring for urinary symptoms, particularly in the month following SGLT2i initiation. More research is urgently needed to determine whether urinary incontinence is an effect modifier of the observed increased risk of urogenital infections seen with SGLT2is. Additionally, future studies of SGLT2i rates of initiation and discontinuation, as well as studies of urinary side effects, should stratify by sex to understand potentially differential impacts of urogenital symptoms across sex. With the current lack of attention to urinary incontinence in the context of SGLT2is, it is unclear if providers are discussing urinary symptoms with patients prior to prescribing SGLT2is. Further research is critically needed to address these issues that can significantly impact the quality of life for millions of people with type 2 diabetes.
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