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

Abstract

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 HbA_1c was not associated with infection risk for SGLT2i, in contrast to DPP4i where risk increased with higher HbA_1c. 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 HbA_1c is not a risk factor for genital infections with SGLT2i.

Keywords: A1C; adherence to medications; candida; non-insulin treated type 2 diabetes.

Figure 1

The proportion of people free from genital infection since drug initiation (A) by sex and medication class (SGLT2i and DPP4i) and (B) by history of prior genital infection and medication class. Number of events by group: (A) DPP4 inhibitor males n=228, DPP4 inhibitor females n=914, SGLT2i males n=371, SGLT2i females n=1092, (B) DPP4 inhibitor no prior infection n=484, DPP4 inhibitor and prior infection n=658, SGLT2i no prior infection n=729, SGLT2i and prior infection n=734. The shaded area represents the 95% CI. DPP4i, dipeptidyl peptidase-4 inhibitor; SGTL2i, sodium-glucoseco-transporter-2 inhibitor.

Figure 2

The association between HbA1c prior to medication initiation and genital infection after initiation of (A) an SGLT2 inhibitor and (B) a DPP4 inhibitor. Analyses are adjusted for age, gender, duration of diabetes, eGFR, BMI, and prior history of infection. The shaded area represents the 95% CI. A median HbA1c value of 8.6% (71mmol/mol) is used as the reference point. BMI, body mass index; DPP4i, dipeptidyl peptidase-4 inhibitor; eGFR, estimated glomerular filtration rate; SGTL2, sodium-glucoseco-transporter-2.

Figure 3

The absolute and relative risk of having a genital infection with an SGLT2i versus DPP4i by risk group. HRs are derived from propensity matched cohorts (online supplementary table S2) and are adjusted for age, gender, duration of diabetes, HbA_1c, eGFR, BMI, and prior history of infection (online supplementary table S8). Numbers in brackets are 95% CIs. BMI, body mass index; DPP4i, dipeptidyl peptidase-4 inhibitor; eGFR, estimated glomerular filtration rate; HR, hazard ratio; SGTL2i, sodium-glucoseco-transporter-2 inhibitor.