Gastrointestinal safety across the albiglutide development programme.
Gastrointestinal (GI) adverse events (AEs) are the most frequently reported treatment-related AEs associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of type 2 diabetes mellitus. The GI safety of albiglutide, a once-weekly GLP-1RA, was assessed using data from five phase III studies. In a pooled analysis of four placebo-controlled trials, the most common GI AEs were diarrhoea (albiglutide, 14.5% vs. placebo, 11.5%) and nausea (albiglutide, 11.9% vs. placebo, 10.3%), with most patients experiencing 1-2 events. The majority were mild or moderate in intensity and their median duration was 3-4 days. Vomiting occurred in 4.9% of patients in the albiglutide vs. 2.6% in the placebo group. For both albiglutide and placebo, serious GI AEs (2.0% vs. 1.5%) and withdrawals attributable to GI AEs (1.7% vs. 1.5%) were low. In a 32-week trial of albiglutide 50 mg weekly versus liraglutide 1.8 mg daily, nausea occurred in 9.9% of patients in the albiglutide group vs. 29.2% in the liraglutide group. Vomiting occurred in 5.0% in the albiglutide vs. 9.3% in the liraglutide group. In conclusion, albiglutide has an acceptable GI tolerability profile, with nausea and vomiting rates slightly higher than those for placebo but lower than those for liraglutide.
Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
L A
LA
Leiter
Annapurna Therapeutics, Philadelphia, PA, USA.
J M
JM
Mallory
PAREXEL International, Research Triangle Park, NC, USA.
T H
TH
Wilson
GlaxoSmithKline, King of Prussia, PA, USA.
R R
RR
Reinhardt
D015746:Abdominal Pain / Q000139:chemically induced; D017326:Clinical Trials, Phase III as Topic; D003248:Constipation / Q000139:chemically induced*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced*; D005764:Gastroesophageal Reflux / Q000139:chemically induced; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D054795:Incretins / Q000009:adverse effects*; D009325:Nausea / Q000139:chemically induced*; D012720:Severity of Illness Index; D014839:Vomiting / Q000139:chemically induced*
D054795:Incretins; C534611:rGLP-1 protein; D052216:Glucagon-Like Peptide 1
GLP-1 receptor agonists; albiglutide; gastrointestinal safety; incretins