Ghanshyam Mali1, Vivek Ahuja2, Kiran Dubey1. 1. Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India. 2. MACR and Global Pharmacovigilance, Sun Pharmaceutical Industries Limited, Gurugram, India.
Abstract
WHAT IS KNOWN AND OBJECTIVE: The use of glucagon-like peptide-1 (GLP-1) analogues has been linked to the risk of thyroid cancer. Spontaneous reports can provide information about rare adverse events occurring after the time of marketing. Our objective was to detect, from the European pharmacovigilance database (EudraVigilance), a signal of thyroid cancer during GLP-1 analogues treatment in patients with diabetes. METHODS: Herein, we analysed all reports of thyroid cancer reported with GLP-1 analogues in EudraVigilance database from their first marketing authorization till 30 January 2020. A case/non-case method was used to assess the association between thyroid cancer and GLP-1 analogues, calculating proportional reporting ratios (PRRs) and their 95% confidence interval (CI) as a measure of disproportionality. The cases were identified with Medical Dictionary for Regulatory Activities (MedDRA) version 22.1. RESULTS AND DISCUSSION: There were 11 243 cases of thyroid cancer and related preferred terms (PTs) in the 6 665 794 reports recorded in EudraVigilance during the study period. GLP-1 analogues were involved in 236 cases. Exenatide, liraglutide and dulaglutide met the criteria to generate a safety signal, suggesting that thyroid cancer is reported relatively more frequently in association with these drugs than with other medicinal products. The association was strongest for liraglutide followed by exenatide with PRR of 27.5 (95% CI, 22.7-33.3) and 22.5 (95% CI, 17.9-28.3), respectively. Disproportionality was also observed for GLP-1 analogues and individual identified preferred term, that is thyroid cancer (N = 111), medullary thyroid cancer (N = 64) and thyroid neoplasm (N = 46) with PRR of 14.4 (95% CI, 11.8-17.4), 221.5 (95% CI, 155.7-315.1) and 35.5 (95% CI, 25.9-48.5), respectively. WHAT IS NEW AND CONCLUSIONS: Our findings showed disproportionality for thyroid cancer, medullary thyroid cancer and thyroid neoplasm in patients treated with GLP-1 analogues. We have found evidence from spontaneous reports that GLP-1 analogues are associated with thyroid cancer in patients with diabetes.
WHAT IS KNOWN AND OBJECTIVE: The use of glucagon-like peptide-1 (GLP-1) analogues has been linked to the risk of thyroid cancer. Spontaneous reports can provide information about rare adverse events occurring after the time of marketing. Our objective was to detect, from the European pharmacovigilance database (EudraVigilance), a signal of thyroid cancer during GLP-1 analogues treatment in patients with diabetes. METHODS: Herein, we analysed all reports of thyroid cancer reported with GLP-1 analogues in EudraVigilance database from their first marketing authorization till 30 January 2020. A case/non-case method was used to assess the association between thyroid cancer and GLP-1 analogues, calculating proportional reporting ratios (PRRs) and their 95% confidence interval (CI) as a measure of disproportionality. The cases were identified with Medical Dictionary for Regulatory Activities (MedDRA) version 22.1. RESULTS AND DISCUSSION: There were 11 243 cases of thyroid cancer and related preferred terms (PTs) in the 6 665 794 reports recorded in EudraVigilance during the study period. GLP-1 analogues were involved in 236 cases. Exenatide, liraglutide and dulaglutide met the criteria to generate a safety signal, suggesting that thyroid cancer is reported relatively more frequently in association with these drugs than with other medicinal products. The association was strongest for liraglutide followed by exenatide with PRR of 27.5 (95% CI, 22.7-33.3) and 22.5 (95% CI, 17.9-28.3), respectively. Disproportionality was also observed for GLP-1 analogues and individual identified preferred term, that is thyroid cancer (N = 111), medullary thyroid cancer (N = 64) and thyroid neoplasm (N = 46) with PRR of 14.4 (95% CI, 11.8-17.4), 221.5 (95% CI, 155.7-315.1) and 35.5 (95% CI, 25.9-48.5), respectively. WHAT IS NEW AND CONCLUSIONS: Our findings showed disproportionality for thyroid cancer, medullary thyroid cancer and thyroid neoplasm in patients treated with GLP-1 analogues. We have found evidence from spontaneous reports that GLP-1 analogues are associated with thyroid cancer in patients with diabetes.