Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation

Introduction: To identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with SGLT2 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 DPP4 inhibitors (DPP4i) in a UK primary care database (CPRD). 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 one year) than DPP4i (1.8%). Key predictors of infection with SGLT2i were; female sex (hazard ratio [HR] 3.64; 95% confidence interval 3.23–4.11) and history of genital infection; <1 year before initiation (HR 4.38; 3.73–5.13), 1-5 years (HR 3.04; 2.64–3.51) and >5 years (HR 1.79; 1.55–2.07). 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 to 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; 1.2-2.1).

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.