Risk of Thyroid Cancer Associated with Use of Liraglutide and Other Antidiabetic Drugs in a US Commercially Insured Population.

BACKGROUND

Quantify association between the glucagon-like peptide-1 receptor agonist liraglutide and risk of thyroid cancer (TC) compared to other antidiabetics.

PATIENTS AND METHODS

Initiators of liraglutide, exenatide, metformin, pioglitazone or groups of dipeptidyl peptidase-4 inhibitors or sulfonylureas were identified in a US health plan (2010-2014) and followed for a median of 17 months. Thyroid cancer cases during follow-up were identified via a validated algorithm. Incidence rates of TC among liraglutide and comparators were assessed using relative risks estimated within propensity score-matched cohorts using intention to treat (ITT) and time on drug analyses. Latency effects and potential surveillance bias were evaluated.

RESULTS

Relative risks from ITT analyses ranged from 1.00 (95% confidence interval (CI) 0.56-1.79) versus metformin to 1.70 (95% CI 1.03-2.81) versus all comparators excluding exenatide. Effect estimates from latency analyses were slightly attenuated. Time on drug analyses suggested no increased risk for either longer duration or higher cumulative dose of liraglutide. Medical record review found 85% were papillary or a follicular variant of papillary or both; 46% were microcarcinomas (≤10 millimeters), which were more prevalent in the liraglutide cohort (67% versus 43% in all comparators).

CONCLUSION

Relative risks were elevated for several comparisons, which should be interpreted cautiously because of potential residual confounding and surveillance bias. Liraglutide cases had smaller thyroid nodules and shorter time-to-diagnosis, suggesting increased surveillance for TC among liraglutide initiators, especially shortly after the drug´s approval. After adjusting the primary analyses (ITT) for latency, no significant elevated risk of TC was observed among liraglutide initiators.

Informations de copyright

© 2021 Funch et al.

Déclaration de conflit d'intérêts

All Optum-affiliated researchers (Funch, Mortimer, Ziyadeh, Seeger, Zhou, Ng, Dore) received support from this contract. As part of this contract, Optum Epidemiology retains the right to publish all results. Funch, Ziyadeh, and Seeger were employed by Optum and hold stock/stock options in the parent company of Optum (UnitedHealth Group, Inc.). Seeger was also involved in a research contract with Boehringer-Ingelheim, during the conduct of the study. Dore was an employee and shareholder of UnitedHealth Group. Ross received payment from Novo Nordisk for case adjudication and for consulting services provided to Optum Epidemiology. He also reports that UBC Corp, which manages the safety monitoring for the Medullary Thyroid Cancer Consortium, pays him personal consultation fees for his time. Major-Pedersen, Bosch-Traberg, and Gydesen are employees of Novo Nordisk A/S. The authors report no other conflicts of interest in this work.