Diabetes – albiglutide
Effective treatments that reliably control blood glucose levels are still much needed
The incidence of Type II diabetes is reaching epidemic levels, and effective treatments that reliably control blood glucose levels are still much needed. In the long term, drugs that modify the disease rather than simply control the symptoms would be extremely advantageous, and one potential therapeutic approach that is receiving much attention is the use of glucogen-like peptide, or GLP-1, agonists. The secretion of this peptide is thought to be impaired in patients with Type II diabetes after they have eaten, but the half-life of the peptide itself is too short.
A couple of analogues are already on the market, but need to be given by daily injections. Another, albiglutide, which should require once-weekly dosing, is being developed by Human Genome Sciences and GlaxoSmithKline.1 Its half-life is increased by fusion with albumin.
Numerous clinical trials have been carried out. In one single blind, randomised dose escalation study, 54 subjects with Type II diabetes were given 9, 16 or 32mg of the drug or placebo on days 1 and 8.2
In a complementary study, a further 46 patients were given a single dose of 16 or 64mg. Significant dose-dependent reductions in 24-hour mean weighted glucose were seen in the 32mg group, and placebo-adjusted fasting glucose fell by 27 and 51mg/dl on days 2 and 9 respectively. No hypoglycaemic events were seen in the patients given albiglutide. Postprandial glucose levels also fell, and the half-life was between six and seven days.
In another randomised, single blind placebo-controlled study, 40 patients were given 15mg or 30mg once a week, 50mg every other week, or 100mg a month, over a four-week treatment period.3 The best results on day 29 were seen with the higher weekly dose, with a 20mmol/dl reduction in fasting plasma glucose, and a 36mmol/dl fall in weighted mean glucose. With the exception of the 100mg dose, the adverse event profile was similar to placebo. Phase III trials are now underway.
references
1. M.A. Bush et al. Diabetes Obesity Metab. 2009, 11, 498
2. J.E. Matthews et al. J. Clin. Endocrinol. Metab. 2008, 93, 4810
3. Y. Seino et al. Curr. Med. Res. Opin. 2009, 25, 3049