No calcitonin change in a person taking dulaglutide diagnosed with pre-existing medullary thyroid cancer

S I Sherman, R T Kloos, R M Tuttle, A Pontecorvi, H Völzke, K Harper, C Vance, J T Alston, A L Usborne, K W Sloop, M Lakshmanan, S I Sherman, R T Kloos, R M Tuttle, A Pontecorvi, H Völzke, K Harper, C Vance, J T Alston, A L Usborne, K W Sloop, M Lakshmanan

Abstract

Background: Glucagon-like peptide-1 receptor agonists, such as dulaglutide, exenatide and liraglutide, are approved to treat Type 2 diabetes mellitus. Although these drugs provide substantial glycaemic control, studies in rodents have prompted concerns about the development of medullary thyroid carcinoma. These data are reflected in the US package insert, with boxed warnings and product labelling noting the occurrence of these tumours after clinically relevant exposures in rodents, and contraindicating glucagon-like peptide-1 receptor agonist use in people with a personal or family history of medullary thyroid carcinoma, or in people with multiple endocrine neoplasia type 2. However, there are substantial differences between rodent and human responses to glucagon-like peptide-1 receptor agonists. This report presents the case of a woman with pre-existing medullary thyroid carcinoma who exhibited no significant changes in serum calcitonin levels despite treatment with dulaglutide 2.0 mg for 6 months in the Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in Diabetes-5 clinical study (NCT00734474).

Case report: Elevated serum calcitonin was noted in a 56-year-old woman with Type 2 diabetes mellitus at the 6-month discontinuation visit in a study of long-term dulaglutide therapy. Retroactive assessment of serum collected before study treatment yielded an elevated calcitonin level. At 3 months post-study, calcitonin level remained elevated; ultrasonography revealed multiple bilateral thyroid nodules. Eventually, medullary thyroid carcinoma was diagnosed; the woman was heterozygous positive for a germline RET proto-oncogene mutation.

Conclusion: The tumour was not considered stimulated by dulaglutide therapy because calcitonin remained stable throughout.

© 2017 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Figures

Figure 1
Figure 1
Immunohistochemistry of human glucagon‐like peptide‐1 receptor (GLP‐1R) knock‐in mouse pancreas (a) at control (40×) magnification, demonstrating membranous GLP‐1R detection in the central cells of the islet (consistent with β‐cell labelling). Haematoxylin and eosin‐stained sections of the patient medullary thyroid cancer (MTC) (b) at low (2.5×) magnification, demonstrating entire tumour nodule with compression of surrounding normal thyroid follicles and (c) and (d) at 20× illustrating both haematoxylin and eosin and immunohistochemistry.

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