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

• Published in: The journal of clinical endocrinology and metabolism Vol. 96; no. 3; pp. 853 - 860
• Main Authors: Hegedüs, Laszlo, Moses, Alan C., Zdravkovic, Milan, Le Thi, Tu, Daniels, Gilbert H.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.03.2011; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adult; Agonists; Biological and medical sciences; Calcitonin; Calcitonin - blood; Cell proliferation; Diabetes; Diabetes Complications - blood; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Dose-Response Relationship, Drug; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; GLP-1 receptor agonists; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - adverse effects; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - blood; Glucagon-Like Peptide 1 - therapeutic use; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Liraglutide; Male; Medical sciences; Middle Aged; Obesity - blood; Receptor mechanisms; Receptors, Glucagon - agonists; Thyroid cancer; Thyroid carcinoma; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Type 2 diabetes; Human; Obesity; Nutrition; Nutrition disorder; Metabolic diseases; Concentration; Medical screening; Glucagon like peptide 1; Hypoglycemic agent; Gastrointestinal hormone; Treatment; Sequential; Analog; Calcitonin; Thyroid hormone; Endocrinology; Nutritional status; Release; Liraglutide
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2010-2318

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.