Introduction To identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with sodium-glucose co-transporter-2 inhibitors (SGLT2i).
Research design and methods We assessed the relationship between baseline characteristics and genital infection in 21 004 people with type 2 diabetes initiating SGLT2i and 55 471 controls initiating dipeptidyl peptidase-4 inhibitors (DPP4i) in a UK primary care database. We assessed absolute risk of infection in those with key risk factors and the association between early genital infection and treatment discontinuation.
Results Genital infection was substantially more common in those treated with SGLT2i (8.1% within 1 year) than DPP4i (1.8%). Key predictors of infection with SGLT2i were female sex (HR 3.64; 95% CI 3.23 to 4.11) and history of genital infection; <1 year before initiation (HR 4.38; 3.73 to 5.13), 1–5 years (HR 3.04; 2.64 to 3.51), and >5 years (HR 1.79; 1.55 to 2.07). Baseline HbA1c was not associated with infection risk for SGLT2i, in contrast to DPP4i where risk increased with higher HbA1c. One-year absolute risk of genital infection with SGLT2i was highest for those with a history of prior infection (females 23.7%, males 12.1%), compared with those without (females 10.8%, males 2.7%). Early genital infection was associated with a similar discontinuation risk for SGLT2i (HR 1.48; 1.21–1.80) and DPP4i (HR 1.58; 1.21–2.07).
Conclusions Female sex and history of prior infection are simple features that can identify subgroups at greatly increased risk of genital infections with SGLT2i therapy. These data can be used to risk-stratify patients. High HbA1c is not a risk factor for genital infections with SGLT2i.
- non-insulin treated type 2 diabetes
- adherence to medications
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Collaborators Additional collaborators in the MASTERMIND consortium: William E Henley; Mike Lonergan; Lauren R Rodgers; Willie T Hamilton; Catherine Angwin; Kennedy J Cruickshank; Andrew J Farmer; Stephen C L Gough; Alastair M Gray; Christopher Hyde; Christopher Jennison; Mark Walker.
Contributors APM, JMD, and AGJ designed the study and drafted the article. BMS and JMD extracted and processed the data. APM and MH analyzed the data. BMS, NAS, RRH, ERP, and ATH contributed to the study design, provided support for the analysis and interpretation of the results. All authors critically revised the article and approved the final version.
Funding The MASTERMIND (MRC APBI Stratification and Extreme Response Mechanism IN Diabetes) consortium is funded by the UK Medical Research Council study grant number MR/N00633X/1. BMS and ATH are supported by the NIHR Exeter Clinical Research Facility. ATH is an NIHR Senior Investigator. ATH is a Wellcome Trust Senior Investigator. AGJ is supported by an NIHR Clinician Scientist award (17/0005624). APM is an NIHR academic clinical fellow. ERP is a Wellcome Trust New Investigator (102820/Z/13/Z). JMD is supported by an Independent Fellowship funded by Research England’s Expanding Excellence in England (E3) fund. RRH is an emeritus UK National Institute for Health Research Senior Investigator.
Competing interests APM declares research support from Eli Lilly and Company, Pfizer, and AstraZeneca. NAS has consulted or been on speakers bureaus for Amgen, Astrazeneca, Boehringer Ingelheim, Janssen, Eli-Lilly, Novo Nordisk, NAPP pharmaceuticals, Pfizer, and Sanofi and received grant support from Boehringer Ingelheim. ERP declares personal fees from Eli Lilly and Company, Novo Nordisk, and AstraZeneca. RRH reports research support from AstraZeneca, Bayer and Merck Sharp & Dohme, and personal fees from Bayer, Intarcia, Merck Sharp & Dohme, Novartis, and Novo Nordisk. AGJ is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Patient consent for publication Not required.
Ethics approval Scientific approval was granted by the CPRD Independent Scientific Advisory Committee (ISAC 13_177R). CPRD has ethical approval from the UK National Research Ethics Service Committee (NRES). No patient identifiable information was available to researchers.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party and are not publicly available. Data used for this study are those collated as part of the Clinical Practice Research Datalink (CPRD). Information on access to this dataset can be found at https://www.cprd.com/Data-access.
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