{
  "abstract": "Objective Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recommended as first-line cardiorenal protective therapy in type 2 diabetes. Because SGLT2is cause glycosuria and increase urine volume, they may exacerbate incontinence symptoms among patients with pre-existing urinary incontinence. Our objective was to determine how many adults meeting guideline indications for SGLT2i have frequent urinary incontinence.Research design and methods We conducted a cross-sectional analysis of National Health And Nutrition Examination Survey (NHANES) participants aged ≥55 with type 2 diabetes in 2013–2020. We determined whether participants met American Diabetes Association guideline indications for an SGLT2i due to heart failure or chronic kidney disease, or due to atherosclerotic cardiovascular disease or high cardiovascular risk (for the latter two cardiovascular indications, GLP-1RAs are guideline-recommended alternative medications). Frequent urinary incontinence was defined by self-report of leaking urine daily/nightly or a few times per week.Results There were 1726 NHANES participants aged ≥55 with type 2 diabetes, representing 16.0 million US adults; 19.6% (95% CI 17.3% to 22.2%) (3.1 million) met indications for an SGLT2i specifically and 50.9% (95% CI 47.2% to 54.7%) (8.2 million) met indications for either an SGLT2i or a GLP-1RA. Among those with indications for an SGLT2i specifically, 32.4% (95% CI 25.9% to 39.8%) had frequent urinary incontinence, representing 333 000 men and 685 000 women. Among those with indications for either an SGLT2i or GLP-1RA, 25.5% (95% CI 20.8% to 30.8%) had frequent urinary incontinence, representing 630 000 men and 1413 000 women.Conclusions Frequent urinary incontinence affects >15% of men and >40% of women aged ≥55 years with guideline indications for SGLT2i. Studies are needed to determine if incontinence increases risk of genital infections when initiating SGLT2is.",
  "authors": [
    {
      "affiliations": [
        "Department of Medicine, Division of Geriatrics, University of California San Francisco, San Francisco, California, USA"
      ],
      "name": "Alexandra K Lee"
    },
    {
      "affiliations": [
        "Department of Internal Medicine, Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut, USA"
      ],
      "name": "Kasia J Lipska"
    },
    {
      "affiliations": [
        "Wake Forest University School of Medicine, Winston-Salem, Carolina, USA"
      ],
      "name": "Kathryn E Callahan"
    },
    {
      "affiliations": [
        "Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA",
        "Department of Family and Community Medicine, University of California San Francisco, San Francisco, California, USA"
      ],
      "name": "Eva Raphael"
    },
    {
      "affiliations": [
        "Department of Medicine, Division of Geriatrics, University of California San Francisco, San Francisco, California, USA",
        "San Francisco VA Medical Center, San Francisco, California, USA"
      ],
      "name": "Sei J Lee"
    }
  ],
  "full_text": "WHAT IS ALREADY KNOWN ABOUT THIS TOPIC Prior studies have shown that roughly 65% of older adults with diabetes have guideline indications for a sodium-glucose cotransporter-2 inhibitor (SGLT2i) or GLP-1RA.However, no studies have examined the prevalence of urinary incontinence among US older adults with diabetes, including those with indications for SGLT2is.WHAT DOES THIS STUDY ADD This study demonstrates that >15% of men and >40% of women aged ≥55 years with guideline indications for SGLT2is have frequent urinary incontinence.HOW MIGHT THIS STUDY AFFECT RESEARCH, POLICY OR PRACTICE Since SGLT2is increase urine volume, providers may want to consider counseling patients about potential impacts on urinary incontinence when starting SGLT2is.Additionally, research is needed to determine if urinary incontinence increases risk of urogenital infections with SGLT2is.Introduction Over the past decade, accumulating evidence of the cardiovascular and renal benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) has transformed SGLT2is from third-line or fourth-line medications to first-line cardiorenal protective therapy for millions of US adults with type 2 diabetes. In both randomized controlled trials 1 and real-world observational studies,2 3 SGLT2is reduce mortality, cardiovascular events, and heart failure hospitalizations, and kidney disease progression. These cardiorenal benefits have been consistent across various subgroups, including by age, sex, and frailty status.1 4 As a result, clinical guidelines from the American Diabetes Association (ADA),5 the Veterans Affairs,6 and the American Association of Clinical Endocrinology7 currently recommend SGLT2is for adults with type 2 diabetes and any one of the following: heart failure, chronic kidney disease, atherosclerotic cardiovascular disease (ASCVD), or high cardiovascular risk (for those with ASCVD or at high cardiovascular risk, glucagon-like peptide 1 receptor agonsists (GLP-1RAs) are another recommended alternative to SGLT2is).However, SGLT2is’ primary mechanism of action of inducing glycosuria may cause particular problems for people with urinary incontinence.8 Initiating SGLT2is leads to an increase in overall urine volume,9 and one recent study found an increase in urology referrals and incontinence symptoms among people using SGLT2is but not other diabetes medications.10 Additionally, it is biologically plausible but unknown whether frequent urinary incontinence increases the established risk of genital mycotic infections with SGLT2is.11 Since urinary symptoms can significantly influence quality of life12 13 and urogenital infections are a leading cause of SGLT2i discontinuation,14 15 a better understanding of urinary incontinence in the context of increasing use of SGLT2is is urgently needed.The objective of this study was to characterize the prevalence of urinary incontinence in adults with type 2 diabetes who meet guideline indications for SGLT2is specifically or either SGLT2is or GLP-1RAs. We conducted analyses stratified across subgroups of age and sex, since prior studies have shown urinary incontinence is more common in women compared with men and in older compared with younger adults.Methods Study population The National Health and Nutrition Examination Survey (NHANES) is a nationally representative cross-sectional study of non-institutionalized US civilians. Our study included NHANES participants from 2013 to 2020 (prepandemic) aged ≥55 years with diagnosed type 2 diabetes (n=2201); we excluded participants who likely had type 1 diabetes by excluding those who self-reported both a diagnosis at age <30 years and insulin use at age <30 years (n=13). We additionally excluded participants who were missing key questionnaire items (n=11), exam findings (body mass index (BMI) or blood pressure, n=283) or laboratory values (estimated glomerular filtration rate (eGFR), albuminuria, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, n=168), for a final sample of 1726.All study participants signed an informed written consent.16SGLT2i guideline indications Using the 2024 ADA Standards of Care, 5 we first identified participants for whom guidelines would indicate an SGLT2i specifically (criteria: self-reported heart failure or chronic kidney disease (CKD), defined by eGFR <60 and urine albumin/creatinine ratio (ACR) ≥30 mg/g). Next, we identified participants for whom guidelines would recommend either an SGLT2i or a GLP-1RA (criteria: established ASCVD defined as self-reported coronary heart disease, heart attack, or stroke; OR at high cardiovascular risk, as defined by the ADA: age ≥55 years with ≥2 additional risk factors: hypertension (systolic blood pressure >130 mm Hg or antihypertensive medications), dyslipidemia (HDL <35 mg/dL or triglycerides >250 mg/dL), BMI ≥30, ACR ≥30 mg/g, current smoking).Urinary incontinence NHANES asks all participants aged ≥20 years: ‘How often do you have urine leakage?’ with possible responses of ‘never’, ‘less than once a month’, ‘a few times a month’, ‘a few times a week’, ‘every day and/or night’. We defined frequent urinary incontinence as reporting urine leakage ‘a few times a week’ or ‘every day and/or night’.Statistical analysis We first examined key demographic and clinical characteristics, overall and stratified by age. We categorized age into two groups: 55–69 years and ≥70 years. Next, we determined the prevalence of urinary incontinence among all participants with type 2 diabetes stratified by sex and age groups. We tested for trends by age using a χ 2 test for linear trend and tested for differences by sex using a χ2 test. Among those adults who were recommended to receive SGLT2is specifically or either SGLT2is or GLP-1RAs, we determined the prevalence of frequent urinary incontinence overall and also stratified on age groups and on sex. We generated estimates of the corresponding number of US adults using US population estimates from the American Community Survey, 2017–2020 (prepandemic).17All analyses were conducted in Stata SE V.18 using survey weights to account for the complex survey design (StataCorp, College Station, Texas, USA).Results There were 1726 NHANES participants with type 2 diabetes, representing 16.0 million US adults. The average age was 67.8 years (SE 0.29) and 44.4% were female ( table 1). The majority were non-Hispanic white (66.0%), 12.6% were Hispanic, 11.8% were non-Hispanic black, 5.5% were of Asian descent, and 4.2% were other race/ethnicity (including multiracial). Mean BMI was 32.2 (SE 0.25) and 10.4% of the participants were current smokers. Additional characteristics and stratification by age group are shown in table 1.Table 1Descriptive characteristics of US adults aged 55 years and older with type 2 diabetes across age categories, NHANES 2013–2020CharacteristicOverall(n=1726)Age category55–69 years(n=1037)70+ years(n=689)Age67.7 (0.29)62.0 (0.25)76.8 (0.30)Female sex44.4%43.6%45.8%Race/ethnicity Hispanic12.6%13.8%10.6% Non-Hispanic white66.0%63.7%69.5% Non-Hispanic black11.8%12.3%11.1% Non-Hispanic Asian5.5%5.4%5.5% Other (including multiracial)4.2%4.8%3.2% BMI32.2 (0.25)33.0 (0.38)30.9 (0.27) HbA1c7.2 (0.06)7.3 (0.09)7.1 (0.06) Smoking10.4%13.4%5.5% Hypertension58.9%57.9%60.5% Cardiovascular disease30.6%26.7%36.6% Heart failure11.1%9.7%13.3% Chronic kidney disease (eGFR <60 and ACR ≥30 mg/g)10.8%6.2%17.9%Guideline indication for SGLT2i* None29.5%30.4%27.9% SGLT2i19.6%14.9%27.0% Either SGLT2i or GLP-1RA50.9%54.6%45.1%Data are mean (SE) or weighted per cent.*By ADA 2024 Standards of Care. Indicated for SGLT2i: self-reported heart failure, OR, both eGFR <60* by CKD-EPI serum creatinine age-sex 2021 equation AND albuminuria (albumin to creatinine ratio ≥30 mg/g). Indicated for either SGLTI2i or GLP-1RA: in NHANES, self-reported coronary heart disease, heart attack, or stroke, OR high risk (defined per ADA criteria: ≥55 years with ≥2 additional risk factors: hypertension (systolic ≥130 mm Hg or antihypertensive medications), dyslipidemia (HDL <35 mg/dL or triglycerides >250 mg/dL), BMI ≥30, albuminuria (ACR ≥30 mg/g), smoking).ACR, albumin/creatinine ratio; ADA, American Diabetes Association; BMI, body mass index; eGFR, estimated glomerular filtration rate; GLP-1RA, glucagon-like peptide 1 receptor agonist; HbA1c, glycated hemoglobin; NHANES, National Health and Nutrition Examination Survey; SGLT2i, sodium-glucose cotransporter-2 inhibitor.Overall, we estimated that 19.6% (95% CI 17.3% to 22.2%), or 3.14 million, US adults aged ≥55 years with type 2 diabetes met indications for SGLT2is and an additional 50.9% (95% CI 47.2% to 54.7%), or 8.16 million, met indications for either an SGLT2i or a GLP-1RA. Those meeting guideline indications for SGLT2is were on average older than those meeting guideline indications for either SGLT2i or GLP-1RA (71.1 years vs 66.7 years); other demographic characteristics were similar (online supplemental eTable 1).SP110.1136/bmjdrc-2025-004929.supp1Supplementary dataAmong US adults with type 2 diabetes, the prevalence of urinary incontinence was higher in women compared with men and higher in older age groups compared with younger age groups (both p<0.001) (online supplemental eFigure 1). Among men, frequent urinary incontinence ranged from 10.7% (95% CI 7.8% to 14.5%) in those aged 55–69 years to 21.0% (95% CI 16.4% to 26.5%) in those aged ≥70 years. Among women, frequent urinary incontinence was 35.1% (95% CI 27.0% to 44.2%) in those aged 55–69 years and 47.7% (95% CI 39.9% to 55.6%) in those aged ≥70 years.Among adults aged ≥55 years with type 2 diabetes who met indications for an SGLT2i specifically, the prevalence of frequent urinary incontinence was 32.4% (95% CI 25.9% to 39.8%) overall. When stratified by age, the prevalence among those meeting indications for an SGLT2i was 22.7% (95% CI 13.8% to 35.1%) in those aged 55–69 years, and 41.0% (95% CI 33.2% to 49.3%) in those aged ≥70 years (figure 1). Among adults with type 2 diabetes who met indications to receive either an SGLT2i or GLP-1RA, the prevalence of frequent urinary incontinence was 25.5% (95% CI 20.8% to 30.8%) overall, 20.6% (95% CI 15.2% to 27.3%) among those aged 55–69 years, and 34.9% (95% CI 27.9% to 42.6%) in those aged ≥70 years.Figure 1Prevalence of frequent urinary incontinence among US adults aged ≥55 years with type 2 diabetes, by age group and SGLT2i guideline indications: NHANES 2013–2020. NHANES, National Health and Nutrition Examination Survey; SGLT2i, sodium-glucose cotransporter-2 inhibitor; GLP-1RA, glucagon-like peptide 1 receptor agonist.The prevalence of frequent urinary incontinence was notably higher in women than in men among participants guideline-indicated for newer cardioprotective treatment (figure 2). Among those with indications for SGLT2is specifically, 19.3% of men (95% CI 11.9% to 29.7%) and 48.4% of women (95% CI 37.5% to 59.4%) had frequent urinary incontinence. Among those with indications to receive either an SGLT2i or a GLP-1RA, 13.9% of men (95% CI 10.1% to 19.0%) and 39.9% of women (95% CI 31.5% to 48.9%) had frequent urinary incontinence. This corresponded to 333 000 men and 685 000 women with urinary incontinence and indications for an SGLT2i specifically, and an additional 630 000 men and 1413 000 women with urinary incontinence and indications to receive either an SGLT2i or a GLP-1RA.Figure 2Prevalence of frequent urinary incontinence among US adults aged ≥55 years with type 2 diabetes, by sex and SGLT2i guideline indications: NHANES 2013–2020. NHANES, National Health and Nutrition Examination Survey; SGLT2i, sodium-glucose cotransporter-2 inhibitor; GLP1-RA, glucagon-like peptide 1 receptor agonist.Among US adults with any SGLT2i indication, the prevalence of frequent urinary incontinence was 15.4% in men (95% CI 11.4% to 20.5%) and 42.3% in women (95% CI 35.1% to 49.8%). This ranged from 9.7% in men aged 55–69 years (95% CI 5.8% to 15.6%) to 52.6% in women aged ≥70 years (95% CI 43.0% to 62.1%) (figure 3).Figure 3Prevalence of frequent urinary incontinence among US adults aged ≥55 years with type 2 diabetes and any SGLT2i indication, by age and sex: NHANES 2013–2020. NHANES, National Health and Nutrition Examination Survey; SGLT2i, sodium-glucose cotransporter-2 inhibitor.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.10Our 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 15Although 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.36There 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.",
  "title": "Urinary incontinence in US adults aged ≥55 years with type 2 diabetes and indications for SGLT2is: NHANES 2013–2020",
  "uid": "b986caf0-0f14-5422-ab3d-000e73230dc6"
}