Chronic liraglutide therapy induces an enhanced endogenous glucagon-like peptide-1 secretory response in early type 2 diabetes.
Sustained exogenous stimulation of a hormone-specific receptor can affect endogenous hormonal regulation. In this context, little is known about the impact of chronic treatment with glucagon-like peptide-1 (GLP-1) agonists on the endogenous GLP-1 response. We therefore evaluated the impact of chronic liraglutide therapy on endogenous GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) response to an oral glucose challenge. A total of 51 people with type 2 diabetes of 2.6 ± 1.9 years' duration were randomized to daily subcutaneous liraglutide or placebo injection and followed for 48 weeks, with an oral glucose tolerance test (OGTT) every 12 weeks. GLP-1 and GIP responses were assessed according to their respective area under the curve (AUC) from measurements taken at 0, 30, 60, 90 and 120 minutes during each OGTT. There were no differences in AUCGIPbetween the groups. By contrast, although fasting GLP-1 was unaffected, the liraglutide arm had ~2-fold higher AUCGLP-1at 12 weeks ( P  < .001), 24 weeks ( P  < .001), 36 weeks ( P  = .03) and 48 weeks ( P  = .03), as compared with placebo. Thus, chronic liraglutide therapy induces a previously unrecognized, robust and durable enhancement of the endogenous GLP-1 response, highlighting the need for further study of the long-term effects of incretin mimetics on L-cell physiology.
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada.|Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada.
Caroline K
CK
Kramer
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada.|Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada.|Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.
Bernard
B
Zinman
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada.
Haysook
H
Choi
Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Philip W
PW
Connelly
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada.|Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada.|Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.
Ravi
0000-0003-1989-027X
R
Retnakaran
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005749:Gastric Inhibitory Polypeptide / Q000097:blood / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000097:blood / Q000378:metabolism; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054795:Incretins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D000069450:Liraglutide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D000069450:Liraglutide; C517652:hemoglobin A1c protein, human

GIP
; 
GLP-1; 
LIBRA
; liraglutide; type 2 diabetes