GLP-1 and Calcitonin Concentration in Humans: Lack of Evidence of Calcitonin Release from Sequential Screening in over 5000 Subjects with Type 2 Diabetes or Nondiabetic Obese Subjects Treated with the Human GLP-1 Analog, Liraglutide
Open Access
- 1 March 2011
- journal article
- research article
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 96 (3), 853-860
- https://doi.org/10.1210/jc.2010-2318
Abstract
Background: Serum calcitonin (CT) is a well-accepted marker of C-cell proliferation, particularly in medullary thyroid carcinoma. Chronic glucagon-like peptide-1 (GLP-1) receptor agonist administration in rodents has been associated with increased serum CT levels and C-cell tumor formation. There are no longitudinal studies measuring CT in humans without medullary thyroid carcinoma or a family history of medullary thyroid carcinoma and no published studies on the effect of GLP-1 receptor agonists on human serum CT concentrations. Aim: The aim of the study was to determine serum CT response over time to the GLP-1 receptor agonist liraglutide in subjects with type 2 diabetes mellitus or nondiabetic obese subjects. Methods: Unstimulated serum CT concentrations were measured at 3-month intervals for no more than 2 yr in a series of trials in over 5000 subjects receiving liraglutide or control therapy. Results: Basal mean CT concentrations were at the low end of normal range in all treatment groups and remained low throughout the trials. At 2 yr, estimated geometric mean values were no greater than 1.0 ng/liter, well below upper normal ranges for males and females. Proportions of subjects whose CT levels increased above a clinically relevant cutoff of 20 ng/liter were very low in all groups. There was no consistent dose or time-dependent relationship and no consistent difference between treatment groups. Conclusions: These data do not support an effect of GLP-1 receptor activation on serum CT levels in humans and suggest that findings previously reported in rodents may not apply to humans. However, the long-term consequences of GLP-1 receptor agonist treatment are a subject of further studies.Keywords
This publication has 23 references indexed in Scilit:
- Glucagon-Like Peptide-1 Receptor Agonists Activate Rodent Thyroid C-Cells Causing Calcitonin Release and C-Cell ProliferationEndocrinology, 2010
- Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination With Metformin and Thiazolidinedione in Patients With Type 2 Diabetes (LEAD-4 Met+TZD)Diabetes Care, 2009
- Liraglutide, a once‐daily human GLP‐1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD‐1 SU)Diabetic Medicine, 2009
- Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 DiabetesDiabetes Care, 2009
- Determination of calcitonin levels in C-cell disease: clinical interest and potential pitfallsNature Clinical Practice Endocrinology & Metabolism, 2009
- Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trialThe Lancet, 2008
- GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo TargetingJournal of Nuclear Medicine, 2007
- Medullary thyroid carcinomaClinical Endocrinology, 2004
- Correlation between gender and spontaneous C-cell tumors in the thyroid gland of the Wistar ratCell and tissue research, 1999
- The Effects of Xenobiotics on the Structure and Function of Thyroid Follicular and C-CellsToxicologic Pathology, 1989