Albiglutide does not impair the counter-regulatory hormone response to hypoglycaemia: a randomized, double-blind, placebo-controlled, stepped glucose clamp study in subjects with type 2 diabetes mellitus

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2015-01, Vol.17 (1), p.82-90
• Main Authors: Hompesch, M., Jones-Leone, A., Carr, M. C., Matthews, J., Zhi, H., Young, M., Morrow, L., Reinhardt, R. R.
• Format: Article
• Language: English
• Subjects: Adult; Beta cells; Blood Glucose - analysis; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Double-Blind Method; Down-Regulation - drug effects; Female; GLP-1 analogue; GLP-1 receptor agonists; Glucagon; Glucagon - blood; Glucagon - metabolism; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - adverse effects; Glucagon-Like Peptide 1 - agonists; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - genetics; Glucagon-Like Peptide 1 - therapeutic use; Glucose; Glucose Clamp Technique; glucose metabolism; Growth hormones; Hormones; Humans; Hyperglycemia - prevention & control; Hypoglycemia; Hypoglycemia - chemically induced; Hypoglycemia - prevention & control; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin - blood; Insulin - metabolism; Insulin Secretion; Male; Middle Aged; Norepinephrine; Pancreas - drug effects; Pancreas - metabolism; Peptides; Placebos; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; type 2 diabetes mellitus; Up-Regulation - drug effects
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12398

Aim To determine if the glucagon‐like peptide‐1 (GLP‐1) receptor agonist albiglutide, once weekly, impairs counter‐regulatory responses during hypoglycaemia. Methods We conducted a randomized, double‐blind, parallel, placebo‐controlled study in subjects with type 2 diabetes mellitus. A single dose of albiglutide 50 mg (n = 22) or placebo (n = 22) was administered on day 1. Glucose was clamped on day 4 (to coincide with the approximate albiglutide maximum plasma concentration) at 9.0, 5.0, 4.0, 3.3 and 2.8 mmol/l (162, 90, 72, 59.4 and 50.4 mg/dl), with a post‐clamp recovery period to 3.9 mmol/l (70 mg/dl). Hormone measurements were made at each plateau and adverse events (AEs) were recorded. Results The counter‐regulatory hormones glucagon, epinephrine, norepinephrine, growth hormone and cortisol were appropriately suppressed when plasma glucose levels were >4.0 mmol/l (>72 mg/dl), but increased in the albiglutide and placebo groups with glucose levels 90 mg/dl), albiglutide increased pancreatic β‐cell secretion of C‐peptide in a glucose‐dependent manner to a greater extent than did placebo, and it was suppressed in each group when levels were