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 mellitus1. Issue 1 (26th October 2014)

• Record Type: Journal Article
• Authors: Hompesch, M.; Jones‐Leone, A.; Carr, M. C.; Matthews, J.; Zhi, H.; Young, M.; Morrow, L.; Reinhardt, R. R.
• Is Part Of: Diabetes, obesity & metabolism. Volume 17:Issue 1(2015:Jan.)
• Page Start: 82
• Page End: 90
• Publication Date: 2014-10-26
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12398
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12398-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dom12398-sec-0001" sec-type="section"> <title>Aim</title> <p id="dom12398-para-0001">To determine if the glucagon‐like peptide‐1 (GLP‐1) receptor agonist albiglutide, once weekly, impairs counter‐regulatory responses during hypoglycaemia.</p> </sec> <sec id="dom12398-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12398-para-0002">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.</p> </sec> <sec id="dom12398-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12398-para-0003">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 <3.3 mmol/l (<59.4 mg/dl) in response to hypoglycaemia. The area under the curve geometric mean ratios (albiglutide : placebo), calculated from the clamped plateau of 4.0 mmol/l (72 mg/dl) to the glucose recovery point, were not significantly different for any of the counter‐regulatory hormones. When plasma glucose levels were >5.0 mmol/l (>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 <4.0 mmol/l (<72 mg/dl). No significant difference between groups was observed in the recovery time to glucose level ≥3.9 mmol/l (≥70 mg/dl). There were no clinically relevant differences in AEs or other safety variables.</p> </sec> <sec id="dom12398-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12398-para-0004">A single 50‐mg dose of albiglutide was well tolerated and did not impair the counter‐regulatory response to hypoglycaemia. These data provide mechanistic evidence supporting the low intrinsic hypoglycaemic potential of albiglutide.</p> </sec> </abstract>