Sodium–glucose cotransporter 2 (SGLT2) inhibitors are oral medications for diabetes that lower blood glucose by preventing the kidneys from reabsorbing glucose, thereby increasing excretion in urine. Approved drugs such as dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin have shown notable benefits for heart and kidney health in patients with type 2 diabetes mellitus (T2DM)(1,2). Despite these advantages, increased urinary glucose excretion may predispose patients to urinary tract infections (UTIs) by creating a favourable environment for Uropathogens such as Escherichia coli and Klebsiella species (3). Patients with diabetes are already at higher risk of UTIs due to immune dysfunction and bladder abnormalities (4-6). This risk may be further influenced by factors such as female sex, advanced age, impaired renal function, and prior history of recurrent infections. Clinical evidence regarding UTI risk with SGLT2 inhibitors remains inconsistent. Some studies report a modest increase in UTIs, particularly with dapagliflozin and canagliflozin, although most cases are mild and manageable (7,8). Conversely, other trials and meta-analyses have found no significant difference compared with placebo or other antidiabetic therapies (9,10). Clinical evidence regarding UTI risk with SGLT2 inhibitors remains inconsistent. Some studies report a modest increase in UTIs, particularly with dapagliflozin and canagliflozin, although most cases are mild and manageable (7,8). Conversely, other trials and meta-analyses have found no significant difference compared with placebo or other antidiabetic therapies (9,10). Empagliflozin generally demonstrates a neutral UTI risk profile (2). Given their substantial cardioprotective and renoprotective benefits, understanding the infection risk associated with individual SGLT2 inhibitors is essential. This study evaluates the association between specific agents, especially dapagliflozin, and UTIs while considering patient-related risk factors to support individualised,evidence-based diabetes care

This retrospective observational study was conducted in the Department of Medicine at F.H. Medical College, Agra, over 18 months. The study included adult patients (≥18 years) diagnosed with type 2 diabetes mellitus (t2dm) who were initiated on sodium–glucose cotransporter 2 (SGLT2) inhibitors during the study period. A total of 125 patients were enrolled. The sample size was calculated using a standard formula for estimating a single proportion, assuming a prevalence of 6%, a 95% confidence interval, and a 5% margin of error, yielding a minimum required sample of 125 participants. Patients aged 18 or older with confirmed T2DM who started on SGLT2 inhibitors- such as dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, or other approved drugs- were eligible for inclusion. Exclusions included patients with documented pre-existing urinary tract infections (UTIS), those on only non-SGLT2 inhibitor antidiabetic therapies, and those unwilling to participate. There were no restrictions based on diabetes duration or prior use of antidiabetic medication. After obtaining informed consent, we recorded demographic details, clinical history, duration of diabetes, previous treatments, and presenting complaints. Baseline tests included routine urine analysis (urine routine and microscopy) to check for pyuria, bacteriuria, or haematuria. Urine culture and sensitivity testing were performed in patients with suspected UTI symptoms to confirm infection, identify causative organisms, and assess antibiotic susceptibility. Additional tests, such as glycated haemoglobin (HbA1c) and renal function tests, were performed to monitor glycaemic control and kidney function during SGLT2 inhibitor therapy. The primary outcome was the occurrence of urinary tract infections after starting SGLT2 inhibitor therapy. UTIs were identified based on clinical symptoms, laboratory findings, and confirmation by urine culture. Secondary outcomes included identifying the causative organisms, their antibiotic sensitivities, and infection severity. Data analysis was performed using SPSS version 21. Continuous variables were presented as mean ± standard deviation, while categorical variables were shown as frequencies and percentages. Appropriate statistical tests examined the relationship between SGLT2 inhibitor use and UTI incidence, with p-values <0.05 indicating significance. The study adhered to institutional ethical standards, ensuring patient confidentiality throughout.

The analysis included 125 patients with type 2 diabetes mellitus, of whom 80 (64.0%) were treated with dapagliflozin and 45 (36.0%) with other SGLT2 inhibitors. The average age was 56.4 ± 10.2 years, and 70 patients (56.0%) were male. The median duration of diabetes was 8 years (IQR 4–12). Poor glycaemic control, defined as HbA1c ≥8%, was observed in 45 patients (36.0%). A history of urinary tract infection (UTI) was reported in 18 patients (14.4%), while 20 patients (16.0%) had reduced renal function (eGFR <60 mL/min/1.73 m²). Baseline demographic and clinical features were similar between the two groups, with no significant differences observed. [see Table 1, Graph:1 (a-f)] The median duration of SGLT2 inhibitor therapy was 10 months (IQR 6–18). Additionally, 28 patients (22.4%) were using medications that increase the risk of UTIS, with a similar distribution across the different treatment groups.[(see Table 2),Graph 2(a-c)]. During the study period, 22 patients experienced at least one UTI episode, with a total prevalence of 17.6% (95% CI: 11.6–25.8). UTIs were observed in 18 out of 80 patients (22.5%) taking dapagliflozin and in 4 out of 45 patients (8.9%) on other SGLT2 inhibitors. The unadjusted odds ratio for developing a UTI with dapagliflozin was 2.98 (95% CI: 0.94–9.43; p = 0.085).[(See table 3,4),(Graph:3)]. Among patients with UTIs, cystitis was the most common symptom at 63.6%, followed by pyelonephritis at 13.6%. Asymptomatic bacteriuria was present in 22.7% of cases. Culture confirmation indicated an infection in 81.8% of patients, with Escherichia coli being the predominant pathogen at 66.7%. Recurrent UTIs were seen in 22.7% of cases, and 9.1% of patients required hospitalisation.[(See table 5,graph:4)]. Based on clinical severity, 63.6% of UTIs were classified as mild and managed with oral antibiotics. Moderate infections accounted for 27.3%, while severe cases needing hospitalization or intravenous antibiotics represented 9.1%.[(See table 6),(graph:5)]. Univariable analysis showed that female sex (p = 0.029), HbA1c ≥8% (p = 0.044), and prior UTI history (p = 0.001) were significantly linked to UTI occurrence. However, age ≥65 years and dapagliflozin use were not statistically significant in this analysis.[(see table:7)(graph:6)]. In the multivariable logistic regression analysis, dapagliflozin use remained independently associated with a higher odds of UTI (adjusted OR 2.50; 95% CI: 1.02–6.12; p = 0.045). Female sex (adjusted OR 2.30; p = 0.037) and a prior UTI history (adjusted OR 3.95; p = 0.007) also served as independent predictors. Meanwhile, poor glycaemic control, age, and reduced renal function were not independently associated with UTI risk.[(see table:8),(graph 7)]. Other adverse events were rare and similar across groups. Genital mycotic infections affected 7.2% of patients, symptoms of volume depletion occurred in 4.8%, and non-severe hypoglycaemia was reported in 5.6%. Discontinuation of the drug due to adverse events occurred in 4.0% of patients.[(see table:9),(graph 8)]. Renal and laboratory parameters remained stable throughout the follow-up period. The average eGFR saw a minor decline from 78.6 ± 18.2 to 76.9 ± 17.8 mL/min/1.73 m² (p = 0.11). However, there were no statistically significant changes in serum creatinine or HbA1c levels.[(see table:10),graph 9(a-c)] . Table 1. Baseline Demographic and Clinical Characteristics (n = 125) Characteristic Overall (n=125) Dapagliflozin (n=80) Other SGLT2i (n=45) Statistical test p-value Age, mean ± SD (years) 56.4 ± 10.2 56.8 ± 10.0 55.6 ± 10.7 t-test 0.54 Male sex, n (%) 70 (56.0%) 43 (53.8%) 27 (60.0%) χ² 0.49 Duration of diabetes, median (IQR), years 8 (4–12) 8 (5–12) 7 (3–11) Mann–Whitney U 0.34 HbA1c ≥8.0%, n (%) 45 (36.0%) 30 (37.5%) 15 (33.3%) χ² 0.61 Prior history of UTI, n (%) 18 (14.4%) 12 (15.0%) 6 (13.3%) χ² 0.81 eGFR <60 mL/min/1.73 m², n (%) 20 (16.0%) 11 (13.8%) 9 (20.0%) χ² 0.35 Table 2. Drug Exposure and Treatment Characteristics Variable Overall (n=125) Dapagliflozin (n=80) Other SGLT2i (n=45) Current SGLT2 inhibitor use 125 (100%) 80 (64.0%) 45 (36.0%) Duration of SGLT2i therapy, median (IQR), months 10 (6–18) 11 (6–18) 9 (5–16) Concomitant UTI-predisposing drugs, n (%) 28 (22.4%) 17 (21.3%) 11 (24.4%) Table 3. Overall Prevalence of UTI Outcome n Percentage (%) 95% CI ≥1 UTI during study period 22 17.6% 11.6 – 25.8 Table 4. UTI Occurrence by Treatment Group (Unadjusted Analysis) Group UTI cases (n) No UTI (n) UTI rate (%) Dapagliflozin (n=80) 18 62 22.5 Other SGLT2 inhibitors (n=45) 4 41 8.9 Unadjusted OR 2.98 95% CI: 0.94–9.43 p = 0.085 Table 5. Clinical and Microbiological Characteristics of UTIs (n = 22) Characteristic n (%) Symptomatic cystitis 14 (63.6%) Pyelonephritis 3 (13.6%) Complicated pyelonephritis 1(4.54%) Uncomplicated pyelonephritis 2 (9.09%) Asymptomatic bacteriuria 5 (22.7%) Culture-confirmed UTI 18 (81.8%) E. coli as causative organism 12 (66.7%) Recurrent UTI (≥2 episodes) 5 (22.7%) Hospitalization for UTI 2 (9.1%) Table 6. Severity of Urinary Tract Infections (n = 22) UTI severity Definition n (%) Mild Uncomplicated cystitis, oral antibiotics 14 (63.6%) Moderate Pyelonephritis without sepsis 6 (27.3%) Severe Hospitalization / IV antibiotics / sepsis 2 (9.1%) Table 7. Univariable Analysis of Risk Factors for UTI Risk factor UTI (n=22) No UTI (n=103) Test p-value Female sex 14 (63.6%) 41 (39.8%) χ² 0.029 Age ≥65 years 6 (27.3%) 22 (21.4%) χ² 0.51 HbA1c ≥8% 12 (54.5%) 33 (32.0%) χ² 0.044 Prior UTI history 8 (36.4%) 10 (9.7%) χ² 0.001 Dapagliflozin use 18 (81.8%) 62 (60.2%) χ² 0.07 Table 8. Multivariable Logistic Regression for Predictors of UTI Predictor Adjusted OR 95% CI p-value Dapagliflozin use 2.50 1.02 – 6.12 0.045 Female sex 2.30 1.05 – 5.02 0.037 HbA1c ≥8% 1.85 0.78 – 4.35 0.16 Prior UTI history 3.95 1.45 – 10.74 0.007 Age (per 10-year increase) 1.12 0.82 – 1.53 0.46 eGFR <60 1.40 0.44 – 4.46 0.57 Table 9. Other Adverse Events and Tolerability (n = 125) Adverse event Overall n (%) Dapagliflozin (n=80) Other SGLT2i (n=45) p-value Genital mycotic infection 9 (7.2%) 6 (7.5%) 3 (6.7%) 0.86 Volume depletion symptoms 6 (4.8%) 4 (5.0%) 2 (4.4%) 0.90 Hypoglycaemia (non-severe) 7 (5.6%) 4 (5.0%) 3 (6.7%) 0.68 Drug discontinuation due to AE 5 (4.0%) 3 (3.8%) 2 (4.4%) 0.86 Table 10. Renal Function and Laboratory Parameters (Baseline vs Current) Parameter Baseline mean ± SD Current mean ± SD Paired test p-value eGFR (mL/min/1.73 m²) 78.6 ± 18.2 76.9 ± 17.8 t-test 0.11 Serum creatinine (mg/dL) 0.98 ± 0.24 1.01 ± 0.27 t-test 0.19 HbA1c (%) 8.0 ± 1.3 7.9 ± 1.2 t-test 0.30

SGLT2 inhibitors have emerged as an important therapeutic option in the management of type 2 diabetes mellitus due to their proven glycaemic, cardiovascular, and renal benefits. However, their mechanism of inducing glucosuria has raised concerns about a possible increase in genitourinary infections, particularly urinary tract infections (UTIs).In the present study, we evaluated the association between dapagliflozin and other SGLT2 inhibitors and the occurrence of UTIs in patients with T2DM. The overall prevalence of UTI in our cohort was 17.6%,indicating that nearly one in six patients experienced at least one episode during the study period. A higher proportion of UTIs was observed among patients receiving dapagliflozin compared with other SGLT2 inhibitors (22.5% vs 8.9%).Although the adjusted analysis showed only a statistical trend, multivariable logistic regression showed that use of dapagliflozinwas independently associated with an increased odd of UTI..These findings are biologically plausible, as increased urinary glucose concentration may facilitate bacterial growth within the urinary tract, particularly in individuals already predisposed to infection (11,12). Our findings are consistent with earlier studies reporting a modest increase in UTI incidence with dapagliflozin therapy. Johnsson et al. (13) observed a higher frequency of UTIs in patients treated with dapagliflozin compared with placebo, although most infections were mild and rarely required discontinuation. Similarly, Zheng et al. (14), in a systematic review and meta-analysis, demonstrated a small but statistically significant increase in UTI risk associated with dapagliflozin. Tanrıverdi et al. (15) also reported an increased occurrence of bacterial UTIs among SGLT2 inhibitor users compared with non-users. In contrast, other large observational studies have not demonstrated a significant increase in UTI risk. Alkabbani et al. (16), in a propensity score–matched population-based cohort study, found no significant association between SGLT2 inhibitor use and UTIs. Likewise, Haghighi et al. (17), in a recent meta-analysis, concluded that although genital mycotic infections were clearly increased, the overall risk of UTIs was not significantly elevated. These discrepancies across studies may reflect differences in patient demographics, baseline infection risk, study design, duration of follow-up, and diagnostic criteria used to define UTIs. In our study, most UTIs were mild and presented as uncomplicated cystitis (63.6%), whereas moderate infections such as pyelonephritis without sepsis accounted for 27.3%, and severe infections requiring hospitalization were uncommon (9.1%). These findings are consistent with previous observational reports indicating that SGLT2 inhibitor–associated UTIs are generally mild to moderate in severity and respond well to standard antimicrobial therapy (18,19). Importantly, no significant deterioration in renal function was observed during follow-up, suggesting that infection episodes did not lead to clinically meaningful renal impairment. Microbiologically, Escherichia coli was the predominant pathogen isolated, in agreement with established epidemiological data in diabetic populations and community-acquired UTIs (11,20). Diabetes itself predisposes individuals to UTIs through impaired host immune defense, autonomic neuropathy leading to incomplete bladder emptying, and enhanced bacterial adherence to uroepithelial cells (12,11). The additional glucosuric effect of SGLT2 inhibitors may further promote bacterial proliferation; however, the absolute increase in risk appears modest. Risk factor analysis demonstrated that female sex and prior history of UTI were strong independent predictors of infection. Previous literature has similarly shown that women with diabetes have an increased risk of recurrent and complicated UTIs (21,11). A prior history of UTI likely reflects underlying host susceptibility or persistent colonization. Although poor glycaemic control was associated with UTI in univariable analysis, it did not remain independently significant after adjustment, suggesting that structural and host-related factors may play a more substantial role than glycaemic parameters alone. Age and reduced renal function were not independent predictors in our cohort. The overall tolerability profile of SGLT2 inhibitors was favourable. Other adverse events were infrequent and comparable between treatment groups. These findings are consistent with the well-established cardiovascular and renal benefits of SGLT2 inhibitors, which often outweigh the relatively small risk of genitourinary infections (1,2). The strengths of this study include its real-world clinical setting, drug-specific comparison, microbiological confirmation of UTIs, and multivariable adjustment for confounding variables. However, certain limitations must be acknowledged. The retrospective design limits causal inference, the modest sample size may reduce statistical power, and the single-center setting may limit generalizability. Residual confounding cannot be entirely excluded. In summary, dapagliflozin was linked to a higher adjusted risk of urinary tract infections (UTIS) compared to other SGLT2 inhibitors in this group; however, the majority of infections were mild and could be managed effectively. Some research supports a small increased risk of UTIS (13,14), while other studies found no significant link (16,17), indicating ongoing debate in the literature. Careful patient selection—especially for women and those with a history of UTIS—along with patient education and regular check-ups, can help maximise treatment benefits while maintaining the significant metabolic and cardiovascular advantages of SGLT2 inhibitors

SGLT2 inhibitors were associated with a modest incidence of urinary tract infections in patients with type 2 diabetes mellitus. Although UTIs were more frequent among dapagliflozin users, most infections were mild and manageable. Female sex and prior history of UTI were significant predictors of infection. Overall, SGLT2 inhibitors demonstrated an acceptable safety profile, supporting their continued use with appropriate patient selection and monitoring. LIMITATIONS This study was limited by its retrospective design and relatively small sample size, which may restrict causal inference and reduce statistical power. Additionally, the single-center setting may limit the generalizability of the findings to broader populations. FUTURE PERSPECTIVES Large-scale prospective cohort studies and randomized controlled trials with longer follow-up are needed to better define the causal relationship between individual SGLT2 inhibitors and UTI risk. Further research should also focus on risk stratification and preventive strategies in high-risk patient groups.

1. Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(11):845–854. 2. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–2128. 3. Liu J, Li L, Li S, et al. Effects of SGLT2 inhibitors on urinary tract and genital infections in type 2 diabetes: a systematic review and meta-analysis. Sci Rep. 2022;12:1235. 4. Zhao Y, Hong D, Zhang M, et al. Risks of urinary tract and genital infections in patients with type 2 diabetes treated with SGLT2 inhibitors: a meta-analysis of 78 randomized trials. Endocrine. 2017;55(2):435–445. 5. Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(4):262–274. 6. Patorno E, Pawar A, Bessette LG, et al. Comparative effectiveness and safety of sodium-glucose cotransporter 2 inhibitors versus glucagon-like peptide 1 receptor agonists in older adults. Diabetes Care. 2021;44(3):826–835. 7. Peters AL, Busch RS, Buse JB. Canagliflozin: a new sodium–glucose cotransporter 2 inhibitor for treatment of type 2 diabetes. Ann Pharmacother. 2014;48(3):360–370. 8. Mahaffey KW, Neal B, Perkovic V, et al. Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS Program trial. Circulation. 2018;137(4):323–334. 9. Geerlings SE. Urinary tract infections in patients with diabetes mellitus: epidemiology, pathogenesis and treatment. Int J Antimicrob Agents. 2008;31(Suppl 1):S54–S57. 10. Nitzan O, Elias M, Chazan B, Saliba W. Urinary tract infections in patients with type 2 diabetes mellitus: review of prevalence, diagnosis, and management. Diabetes Metab Syndr Obes. 2015;8:129–136. 11. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: 2010 update. Clin Infect Dis. 2011;52(5):e103–e120. 12. Mnif MF, Kamoun M, Kacem FH, et al. Complicated urinary tract infections associated with diabetes mellitus: pathogenesis, diagnosis and management. Indian J Endocrinol Metab. 2013;17(3):442–445. 13. Johnsson KM, Ptaszynska A, Schmitz B, Sugg J, Parikh SJ, List JF. Urinary tract infections in patients with diabetes treated with dapagliflozin. J Diabetes Complications. 2013;27(5):473–478. 14. Zheng Z, He D, Chen J, et al. Risk of urinary tract infection in patients with type 2 diabetes mellitus treated with dapagliflozin: a systematic review and meta-analysis of randomized controlled trials. Clin Drug Investig. 2023;43(4):209–225. 15. Tanrıverdi M, Baştemir M, Demirbakan H, et al. Association of SGLT-2 inhibitors with bacterial urinary tract infection in type 2 diabetes. BMC Endocr Disord. 2023;23(1):211. 16. Alkabbani W, Zongo A, Minhas-Sandhu JK, et al. Sodium-glucose cotransporter-2 inhibitors and urinary tract infections: a propensity score–matched population-based cohort study. Can J Diabetes. 2022;46(4):392–403. 17. Haghighi R, Zaman Samghabadi N, Raeisi Jaski R, et al. Investigating the association between SGLT-2 inhibitors and the risk of urinary tract infection: a systematic review and meta-analysis. J Renal Inj Prev. 2024;13(1):e32276. 18. Azhar M, Hanif M, Rafi S, et al. Frequency of urinary tract infections in type 2 diabetes patients taking SGLT2 inhibitors. J Pharm Neg Results. 2023;14(4):95–99. 19. Aswini S, Ezhumalai B, Hanusha V, et al. Prevalence of adverse effects associated with dapagliflozin in a tertiary care centre. Int J Pharm Pharm Sci. 2024;17(12):147–150. 20. Nicolle LE. Uncomplicated urinary tract infection in adults including uncomplicated pyelonephritis. Urol Clin North Am. 2008;35(1):1–12. 21. Gorter KJ, Hak E, Zuithoff NP, Hoepelman AI, Rutten GE. Risk of recurrent acute lower urinary tract infections and prescription pattern of antibiotics in women with and without diabetes in primary care. Fam Pract. 2010;27(4):379–385.