Evaluation of vulvovaginal symptoms and Candida colonization in women with type 2 diabetes mellitus treated with canagliflozin, a sodium glucose co-transporter 2 inhibitor

Abstract

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.

Trial registration: ClinicalTrials.gov identifier: NCT00642278.

Keywords:

• Canagliflozin
• Diabetes
• Sodium glucose co-transporter 2 inhibitor
• Vulvovaginal candidiasis

Transparency

Declaration of funding

The DIA 2001 study was funded by Janssen Research & Development, LLC. Editorial assistance was provided by Phase Five Communications Inc., funded by Janssen Global Services, LLC.

Declaration of financial/other relationships

K.U. and K.W. are employees of Janssen Research & Development, LLC. Y.Z. was formerly an employee of Janssen Research & Development, LLC. P.N. is a consultant to Janssen Research & Development, LLC.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

Canagliflozin is being developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation. Editorial assistance was provided by Phase Five Communications Inc., and funded by Janssen Global Services, LLC.

We, the authors, dedicate this paper to our co-author, Yue Zhao, PhD, who recently passed away. Yue was the statistician on the study, and held the position of senior manager at the time of her death. We extend our greatest sympathy to Yue's family and friends.

This work has been previously presented as a poster ‘Effects of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor on vulvovaginal candidal colonization in patients with type 2 diabetes mellitus (T2DM)’ at the American Diabetes Association 71st Scientific Sessions, San Diego, CA, USA, June 24–27, 2011.