Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies

Abstract

Objective:

To characterize genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) using pooled data from Phase 3 studies.

Research design and methods:

Genital mycotic infections with canagliflozin 100 and 300 mg were evaluated in Population 1 (N = 2313; mean exposure [weeks]: canagliflozin, 24.3; placebo, 23.8), including patients from four placebo-controlled studies, and Population 2 (N = 9439; mean exposure [weeks]: canagliflozin, 68.1; control, 64.4), including patients from eight placebo/active-controlled studies (including older patients and those with renal impairment or high cardiovascular disease risk).

Clinical trial registration:

ClinicalTrials.gov identifier: NCT01081834.

ClinicalTrials.gov identifier: NCT01106625.

ClinicalTrials.gov identifier: NCT01106677.

ClinicalTrials.gov identifier: NCT01106690.

ClinicalTrials.gov identifier: NCT01032629.

ClinicalTrials.gov identifier: NCT01064414.

ClinicalTrials.gov identifier: NCT01106651.

ClinicalTrials.gov identifier: NCT00968812.

Main outcome measures:

Adverse events suggestive of genital mycotic infections were recorded, with additional information collected using supplemental electronic case report forms.

Results:

In Population 1, genital mycotic infection incidence was higher with canagliflozin 100 and 300 mg than placebo (95% confidence intervals excluded zero) in females (10.4%, 11.4%, 3.2%) and males (4.2%, 3.7%, 0.6%). These were generally mild to moderate in intensity, none were serious, and few led to discontinuation. Most events with canagliflozin were treated with antifungal therapies, and median symptom duration following treatment initiation was similar across groups; few patients had >1 event (females, 2.3%; males, 0.9%). Findings with canagliflozin 100 and 300 mg versus control were similar in Population 2 (females: 14.7%, 13.9%, 3.1%; males: 7.3%, 9.3%, 1.6%); a low proportion of males underwent circumcision across groups. Most events with canagliflozin occurred within the first 4 months in females and first year in males; no consistent evidence of dose dependence was observed. Key limitations included lack of laboratory confirmation for most events and variable treatment methods.

Conclusions:

Genital mycotic infection incidences were higher with canagliflozin than control in patients with T2DM; events were generally mild to moderate in intensity and responded to standard treatments.

Keywords::

• Canagliflozin
• Genital mycotic infection
• Sodium glucose co-transporter 2 (SGLT2) inhibitor
• Type 2 diabetes mellitus

Transparency

Declaration of funding

The studies described in this manuscript were sponsored by Janssen Research & Development LLC. The sponsor had a role in the study design and conduct, and in data collection, analysis, and interpretation. The authors prepared the report with editorial assistance funded by the sponsor. All authors had full access to study data, were responsible for the integrity of the data and the accuracy of the data analysis, and reviewed, edited, and approved the report for publication.

Declaration of financial or other relationships

P.N. and J.D.S. are consultants for Janssen. A.F., C.M., G.C., K.W., and K.U. are full-time employees of Janssen Research & Development LLC. C.M. is a holder of Johnson & Johnson stock and stock options.

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

The authors thank all investigators, study teams, and patients for participating in these studies. Editorial support was provided by Katie McClendon, PhD, of MedErgy, and was funded by Janssen Global Services LLC. Canagliflozin has been developed by Janssen Research & Development LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation.

Prior presentation: This analysis was previously presented, in part, in abstract form at the 73rd Scientific Sessions of the American Diabetes Association, Chicago, IL, 21–25 June 2013; and the 49th Annual Meeting of the European Association for the Study of Diabetes, Barcelona, Spain, 23–27 September 2013.

Preferred terms used in the analysis of female and male genital mycotic infections.