Sodium‐glucose co‐transporter‐2 inhibitors and the risk of urosepsis: A multi‐site, prevalent new‐user cohort study

Fisher, Anat; Fralick, Michael; Filion, Kristian B.; Dell’Aniello, Sophie; Douros, Antonios; Tremblay, Éric; Shah, Baiju R.; Ronksley, Paul E.; Alessi‐Severini, Silvia; Hu, Nianping; Bugden, Shawn; Ernst, Pierre; Lix, Lisa M.

doi:10.1111/dom.14082

Cited by 16 publications

(18 citation statements)

References 34 publications

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“…However, a meta-analysis and two cohort studies all reported no increase in risk for UTI. 12 – 14 Rather, SGLT2i use has been associated with increased glucosuria and risk for genital mycotic infections. 11 , 12 , 20 – 22 When compared with DPP-4i initiation, SGLT2i use was associated with increased risk for genital mycotic infection without an increased risk for UTI in older adults, though events were still rare.…”

Section: Discussionmentioning

confidence: 99%

Sodium-glucose cotransporter-2 inhibitors and risk for genitourinary infections in older adults with type 2 diabetes

Varshney¹,

Billups

Saseen

et al. 2021

Therapeutic Advances in Drug Safety

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Background and aims: Although landmark clinical trials have demonstrated an increased risk for genitourinary infection (GUI) after initiation of sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy that led to an FDA label warning, real world findings have been inconsistent and evidence specifically in older adults is lacking. The objective of the study was to examine the incidence of GUI in patients aged 65 years or older initiated on SGLT2i compared with glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy at a large academic health system. Methods: A retrospective population-based cohort study was conducted using electronic health records of patients aged 65 years and older with a diagnosis of type 2 diabetes mellitus. Patients newly initiated on SGLT2i or GLP1-RA therapy with estimated glomerular filtration rate (eGFR) ⩾30 mL/min per 1.73 m² and active within the health system for at least 1 year prior to initiation were included. We compared the incidence of inpatient, emergency room, or outpatient diagnosis of GUI (bacterial and mycotic) within 6 months of SGLT2i or GLP1-RA initiation. A chi-square or Fisher’s exact test were used to analyze between-group differences for categorical variables, while a t-test was used for continuous variables. A Cox proportional hazards model was used to estimate the impact of confounding variables on the primary outcome. Results: One hundred and thirty-three patients were initiated on SGLT2i therapy and 341 patients newly initiated on GLP1-RA therapy. After adjusting for differences in age, A1c, body mass index, eGFR, race and sex, there was no statistically significant difference in GUI incidence within 6 months of SGLT2i versus GLP1-RA initiation (3.8% versus 6.5%, adjusted hazard ratio: 0.784, 95% confidence interval 0.260–2.367). Conclusion: We found no increased risk of composite GUI within 6 months of initiating SGLT2i compared with GLP1-RA therapy. These real-world data in older adults add to previous findings, which suggest no increased risk of urinary tract infection with SGLT2i initiation. Plain language summary A class of antidiabetic medications and risk for genitourinary infections in older adults with type 2 diabetes Older adults with type 2 diabetes often benefit from a class of antidiabetic medications known as sodium-glucose cotransporter-2 inhibitors (SGLT2is) which help to lower blood glucose, decrease risk for cardiovascular disease and prevent kidney disease progression. However, there is concern that these medications may increase risk for urinary tract infections and/or genital fungal infections in older adults based on clinical trial evidence. Our study evaluated the real-world occurrence of these safety events in patients aged 65 years or older who were newly started on these medications. We compared these patients with a group of patients newly started on an alternative class of antidiabetic agents which are not expected to increase risk for infections, known as glucagon-like peptide-1 receptor agonists (GLP1-RA). In our study, we included 133 patients who started an SGLT2i and 341 patients who started a GLP1-RA at a large teaching hospital. We evaluated the occurrence of infection up to 6 months after initiation of these mediations. We found no significant difference in infection rate between these two groups. We conclude in the study that the use of SGLT2i in older adults was not associated with increased risk for urinary tract infections or genital fungal infections when compared with GLP1-RA use.

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Section: Discussionmentioning

confidence: 99%

Sodium-glucose cotransporter-2 inhibitors and risk for genitourinary infections in older adults with type 2 diabetes

Varshney¹,

Billups

Saseen

et al. 2021

Therapeutic Advances in Drug Safety

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“…Data were from an existing multi-database retrospective cohort study conducted by the Canadian Network for Observational Drug Effect Studies (CNODES) [ 12 ], a pan-Canadian network that examines questions of drug safety and effectiveness at the request of government stakeholders. This cohort study investigated the safety and effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors, a new class of antidiabetic medications, compared to dipeptidyl peptidase-4 (DPP-4) inhibitors [ 13 – 16 ]. Databases from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Quebec) and the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) were used.…”

Section: Methodsmentioning

confidence: 99%

“…The cohort has been described in detail elsewhere [ 13 – 16 ]. Briefly, the cohort for the initial multi-database study included patients who received a prescription for a SGLT2 inhibitor or a DPP-4 inhibitor.…”

Section: Methodsmentioning

confidence: 99%

Validity of an algorithm to identify cardiovascular deaths from administrative health records: a multi-database population-based cohort study

Lix

Sobhan

St-Jean

et al. 2021

BMC Health Serv Res

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Background Cardiovascular death is a common outcome in population-based studies about new healthcare interventions or treatments, such as new prescription medications. Vital statistics registration systems are often the preferred source of information about cause-specific mortality because they capture verified information about the deceased, but they may not always be accessible for linkage with other sources of population-based data. We assessed the validity of an algorithm applied to administrative health records for identifying cardiovascular deaths in population-based data. Methods Administrative health records were from an existing multi-database cohort study about sodium-glucose cotransporter-2 (SGLT2) inhibitors, a new class of antidiabetic medications. Data were from 2013 to 2018 for five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, Quebec) and the United Kingdom (UK) Clinical Practice Research Datalink (CPRD). The cardiovascular mortality algorithm was based on in-hospital cardiovascular deaths identified from diagnosis codes and select out-of-hospital deaths. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for the cardiovascular mortality algorithm using vital statistics registrations as the reference standard. Overall and stratified estimates and 95% confidence intervals (CIs) were computed; the latter were produced by site, location of death, sex, and age. Results The cohort included 20,607 individuals (58.3% male; 77.2% ≥70 years). When compared to vital statistics registrations, the cardiovascular mortality algorithm had overall sensitivity of 64.8% (95% CI 63.6, 66.0); site-specific estimates ranged from 54.8 to 87.3%. Overall specificity was 74.9% (95% CI 74.1, 75.6) and overall PPV was 54.5% (95% CI 53.7, 55.3), while site-specific PPV ranged from 33.9 to 72.8%. The cardiovascular mortality algorithm had sensitivity of 57.1% (95% CI 55.4, 58.8) for in-hospital deaths and 72.3% (95% CI 70.8, 73.9) for out-of-hospital deaths; specificity was 88.8% (95% CI 88.1, 89.5) for in-hospital deaths and 58.5% (95% CI 57.3, 59.7) for out-of-hospital deaths. Conclusions A cardiovascular mortality algorithm applied to administrative health records had moderate validity when compared to vital statistics data. Substantial variation existed across study sites representing different geographic locations and two healthcare systems. These variations may reflect different diagnostic coding practices and healthcare utilization patterns.

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“…[25], Urologen oft nicht an der Therapie weiblicher FG Patienten beteiligt sind [26], Candida species oft in den Wunden der FG Patienten nachgewiesen werden, sodass eine primäre antimykotische Therapie evaluiert werden sollte [27] und dass die hyperbare Oxygenierung (HBO) als auch der vakuum-assistierte Wundverschluss (VAC) positive Effekte auf die Behandlungsergebnisse haben [28,32]. Die oben angesprochene Kohortenstudie konnte ebenfalls kein erhöhtes Risiko für FG bei der Einnahme von SGLT2-und DPP4-Hemmern (Antidiabetika) nachweisen [31].…”

Section: Ergebnisse Aus Den Retrospektiven Studienunclassified

“…Mit diesem Fakt beschäftigen sich insgesamt 4 der inkludierten Arbeiten. Zusammenfassend konnte in allen Studien kein signifikanter Zusammenhang mit diesen Antidiabetika aufgezeigt werden [31,36,37,41]. [38].…”

Section: Ergebnisse Des Systematischen Reviewsunclassified

Neue Aspekte zur Fournierschen Gangrän – Ein Rapid Review

2021

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ZusammenfassungDie Fourniersche Gangrän (FG) ist eine sporadische, lebensbedrohliche, nekrotisierende Infektion des Perineums, der Perinealregion und des äußeren Genitales. Aus der Literatur gibt es einige Hinweise darauf, dass die Prognose der Erkrankung in den letzten Jahren nicht wesentlich verbessert werden konnte. Daher wurde eine schnelle Evidenzanalyse mittels Literaturrecherche in MEDLINE aus den aktuellen Publikationen des Jahres 2020 durchgeführt, um mittels neuer Aspekte zu ermöglichen, die Versorgungssituation der betroffenen Patienten zu verbessern und weitere Forschungsvorhaben ideal zu planen. Insgesamt konnten für dieses Review 18 Publikationen berücksichtigt werden. Bei 15 dieser Arbeiten handelt es sich um Orginalarbeiten sowie 3 systematische Reviews. Bez. der Orginalarbeiten handelt es sich um 12 retrospektive Fallserien, 2 epidemiologische und eine prospektive Studie. 2 der systematischen Reviews inkludieren ebenfalls eine Metaanalyse. Die Mehrzahl der Autoren dieser Publikationen kommt unter anderem zu der Schlussfolgerung, dass die FG weiterhin eine ernsthafte Erkrankung mit teils inakzeptablen Mortalitätsraten für die moderne Medizin ist und es in der Therapie weiterhin Optimierungsbedarf gibt. Weiterhin wurden neue Risikofaktoren identifiziert, die mit einer erhöhten Mortalität bei FG Patienten assoziiert sind. Es handelt sich um eine Dyslipoproteinämie, Diabetes mellitus, Herzerkrankungen und akutes sowie chronisches Nierenversagen. 4 der inkludierten Arbeiten untersuchten den Zusammenhang des Auftretens von FG und der Einnahme oraler Antidiabetika, SGLT2- sowie DPP4-Hemmern. Keine Studie konnte dabei einen signifikanten Zusammenhang nachweisen, insbesondere eine Metaanalyse mit 84 Studien nicht. Vielversprechende Konzepte für die Wundbehandlung sind die hyperbare Oxygenierung (HBO), der vakuum-assistierte Wundverschluss und Wundkonditionierung mittels Larven. Zusammenfassend ist die FG ein seltenes, aber immer noch potenziell vital bedrohliches Krankheitsbild. Die Prognose konnte in den letzten Jahren nicht verbessert werden. Daher ist eine weitere Therapieoptimierung dringend erforderlich. Dies kann nur durch weitere Studien erreicht werden. Aufgrund der Seltenheit der Erkrankung sehen wir die Möglichkeit dies mit einer nationalen Registerstudie zu erreichen. Zusätzlich können aus dem Register Risikostratefizierungen erarbeitet werden, welche Patienten z. B. von einer Therapie in einem Zentrum oder bestimmten Wundkonditionierungen profitieren.

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Sodium‐glucose co‐transporter‐2 inhibitors and the risk of urosepsis: A multi‐site, prevalent new‐user cohort study

Abstract: Short running title "SGLT2i and urosepsis" Word Count: 3475; Abstract Word Count: 249, Number of references 40, Number of tables 3, Number of figures 2

Cited by 16 publications

References 34 publications

Sodium-glucose cotransporter-2 inhibitors and risk for genitourinary infections in older adults with type 2 diabetes

Sodium-glucose cotransporter-2 inhibitors and risk for genitourinary infections in older adults with type 2 diabetes

Validity of an algorithm to identify cardiovascular deaths from administrative health records: a multi-database population-based cohort study

Neue Aspekte zur Fournierschen Gangrän – Ein Rapid Review

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