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Diabetes Obes Metab. 2015 Jan;17(1):82-90. doi: 10.1111/dom.12398. Epub 2014 Oct 26.

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.

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1
Profil Institute for Clinical Research, Inc., Chula Vista, CA, USA.

Abstract

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 <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.

CONCLUSIONS:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01475734.

KEYWORDS:

GLP-1 analogue; glucose metabolism; type 2 diabetes mellitus

PMID:
25263215
DOI:
10.1111/dom.12398
[Indexed for MEDLINE]

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