title: Safety and tolerability of exenatide once weekly in patients with type 2 diabetes: an integrated analysis of 4,328 patients.
abstract: BACKGROUND
  Exenatide once weekly (QW) is a glucagon-like peptide-1 receptor agonist (GLP-1RA) for the treatment of type 2 diabetes. Safety and tolerability are key considerations in treatment selection. This analysis examines the safety and tolerability profile of exenatide QW, other approved GLP-1RAs (exenatide twice daily and liraglutide once daily), and a pooled population of commonly used non-GLP-1RA treatments.
  
  
  METHODS
  Intent-to-treat populations from eight randomized Phase III trials with 24-week and 30-week comparator-controlled periods were analyzed. Data were pooled for exenatide QW, exenatide twice daily, and non-GLP-1RA comparator groups; comparisons between exenatide QW and liraglutide were analyzed separately to better match study groups. The incidence of treatment-emergent adverse events with 95% confidence intervals and exposure-adjusted incidence were calculated. Duration and recurrence were analyzed for gastrointestinal adverse events and adverse events of special interest.
  
  
  RESULTS
  Incidences of serious adverse events did not differ between treatments. Discontinuations due to adverse events occurred numerically less frequently with exenatide QW than with other GLP-1RAs but numerically more frequently than with non-GLP-1RA comparators. The most frequent adverse events in the GLP-1RA groups were gastrointestinal and generally mild, with decreasing incidence over time. Gastrointestinal adverse event incidences appeared lower with exenatide QW versus other GLP-1RAs and greater than with non-GLP-1RA comparators. Injection site-related adverse events seemed highest with exenatide QW, but generally did not lead to withdrawal and abated over time. Hypoglycemia was infrequent overall, but occurred numerically more frequently in the non-GLP-1RA comparator group and increased with concomitant sulfonylurea use. Pancreatitis, thyroid cancer, renal failure, and gallbladder disease were rarely reported.
  
  
  CONCLUSIONS
  The overall safety and tolerability profile of exenatide QW was similar to that of other GLP-1RAs, with improved gastrointestinal tolerability. The safety and tolerability profile of exenatide QW compared with non-GLP-1RA comparators was similar overall, with the exception of a lower incidence of hypoglycemia and anticipated differences in gastrointestinal and injection site-related adverse events.
authors.affiliation: Clinical Development, Bristol-Myers Squibb, San Diego, CA, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: MacConell
authors.affiliation: Medical Writing, Bristol-Myers Squibb, San Diego, CA, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: Gurney
authors.affiliation: Clinical Development, Bristol-Myers Squibb, San Diego, CA, USA.
authors.forename: Jaret
authors.initials: J
authors.lastname: Malloy
authors.affiliation: Biostatistics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Safety, Bristol-Myers Squibb, San Diego, CA, USA.
authors.forename: Orville
authors.initials: O
authors.lastname: Kolterman
keywords: adverse events; glucagon-like peptide-1 receptor agonist; hyperglycemia; hypoglycemia