BACKGROUND/OBJECTIVE: Women with type 2 diabetes mellitus (T2DM) are at 
increased risk for vaginal Candida colonization, perhaps because of glucosuria. 
Sodium glucose co-transporter 2 (SGLT2) inhibitors, in development for the 
treatment of T2DM, improve glycemic control by increasing urinary glucose 
excretion. Vaginal Candida colonization and symptomatic vulvovaginal adverse 
events (VVAE) were assessed in females with T2DM treated with canagliflozin, a 
SGLT2 inhibitor.
METHODS: In a double-blind study, subjects with T2DM and inadequate glycemic 
control on metformin were randomized to placebo; canagliflozin 50, 100, 200, 
300 mg daily or 300 mg twice daily; or sitagliptin 100 mg daily for 12 weeks. 
Vaginal swabs for Candida culture were collected from 198 female subjects at 
baseline and week 12, and during the trial if symptoms consistent with 
vulvovaginal candidiasis occurred.
RESULTS: At baseline, 23/198 (12%) females had vaginal cultures positive for 
Candida (C. glabrata: 14; C. albicans: 5; other: 4), with age ≤55 years 
associated with increased risk (odds ratio [OR], 3.5; 95% confidence interval 
[CI], 1.1-10.7). Of those with negative cultures at baseline, 31% of 
canagliflozin and 14% of placebo/sitagliptin subjects converted to positive at 
week 12 (OR, 2.8; 95% CI, 1.0-7.3 for canagliflozin vs. placebo/sitagliptin). 
Two placebo/sitagliptin (3%) and 16 canagliflozin subjects (10%) experienced 
VVAE. Positive vaginal culture for Candida species at baseline was a risk factor 
for VVAE (OR, 9.1; 95% CI, 2.4-34.0). All 9/9 subjects in the canagliflozin 
group with a vaginal culture taken at the time of the VVAE were positive for 
Candida species. Most VVAE were treated with antifungal therapy and resolved 
without study drug interruption; none led to discontinuation. Study limitations 
include small population, short duration, and not obtaining cultures in all 
women with VVAE.
CONCLUSION: Canagliflozin treatment was associated with an increase in vaginal 
colonization with Candida species and in VVAE in women with T2DM.