Is there an association between liraglutide use and female breast cancer in a real-world setting?

Abstract

Background

Liraglutide is a human glucagon-like peptide-1 receptor agonist approved for treatment of adults with type 2 diabetes mellitus at a maximum dose of 1.8 mg/day (Victoza^®) and more recently at 3.0 mg/day for weight management (Saxenda^®). During the evaluation of liraglutide for approval in weight management, a minor imbalance in the numbers of reported breast neoplasms was observed, motivating the present study. Our objective was to quantify the association between liraglutide and incidence of breast cancer (BC) among women in a real-world setting.

Patients and methods

Women initiating liraglutide or other antidiabetic therapies and who were enrolled in a large US health plan (2010–2014) were included. Comparisons of BC incidence rates were made between matched cohorts of initiators of liraglutide and cohorts of initiators of exenatide, metformin, pioglitazone, sulfonylureas, and dipeptidyl peptidase-4 inhibitors separately and as two “all comparators” groupings: with or without exenatide. Women with two or more claims with BC diagnosis codes within 61days of each other were identified as possible cases, with additional confirmation by clinician review of comprehensive claims listings. Propensity score matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed via Poisson regression. A latency analysis was performed.

Results

Relative risks for BC for liraglutide vs comparators from the ITT analyses ranged from 0.90 (95% CI: 0.67–1.22) for both the “all comparator” and “all comparator except exenatide” cohorts to 1.46 (95% CI: 0.96–2.22) relative to exenatide. Latency analyses excluding the first year of follow-up yielded slightly attenuated point estimates. The TOD analyses of cumulative use of liraglutide suggested no increased risk of BC.

Conclusion

Neither the ITT (overall or latency analysis) nor cumulative TOD analyses suggested an elevated risk of BC among liraglutide initiators. Short length of follow-up and the potential for confounding by unmeasured factors limit the full assessment of long-term risk.

Keywords:

• glucagon-like peptide-1 receptor agonist
• type 2 diabetes
• administrative claims
• intention-to-treat
• time-on-drug

Acknowledgments

The authors would like to acknowledge the contributions of Nicole Brooks for her project oversight and Danielle Cupka for her technical assistance in preparing this manuscript.

This study was funded by a research contract with Novo Nordisk A/S. As part of this contract, Optum Epidemiology retains the right to publish all results. Because this work was undertaken to meet a regulatory requirement, Novo Nordisk reviewed and commented on the protocol and statistical analysis plan underlying this work as well as the final report. The original study design and analytic plan required US FDA approval.

Author contributions

DDD had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Because this work was in response to a regulatory (European Medicines Agency) request, Novo Nor-disk reviewed and commented on the protocol and statistical analysis plan underlying this work. Study concept and design: DDD, DF, and KM; acquisition of data: LL and HN; analysis and interpretation of data: DDD, DF, KM, LL, and HN; drafting of the manuscript: DF; and critical revision of the manuscript for important intellectual content: DDD, KM, AM-P, AHO, and MSK. All authors contributed toward data analysis, drafting and revising the paper, gave final approval of the version to be published and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Supplementary materials

Figure S1 Time to diagnosis: liraglutide and all comparators.

Figure S2 Time to diagnosis: liraglutide and all comparators excluding exenatide.

Figure S3 Time to diagnosis: liraglutide and exenatide.

Figure S4 Time to diagnosis: liraglutide and DPP4i.

Abbreviation: DPP4i, dipeptidyl peptidase-4 inhibitor.

Figure S5 Time to diagnosis: liraglutide and metformin.

Figure S6 Time to diagnosis: liraglutide and sulfonylureas.

Figure S7 Time to diagnosis: liraglutide and pioglitazone.

Table S1 Distribution of breast cancer cases and patients by age group and matched cohorts