Glargine plus exenatide does not increase hypoglycemia in type 2 diabetes

June 29, 2011

The combination of insulin glargine and the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide was associated with significant reductions in glycosylated hemoglobin (HbA1c) without increasing hypoglycemia in patients with poorly controlled type 2 diabetes.

The combination of insulin glargine and the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide was associated with significant reductions in glycosylated hemoglobin (HbA1c) without increasing hypoglycemia in patients with poorly controlled type 2 diabetes.
     Among 281 patients who had exenatide added to an existing glargine regimen, the mean reduction in HbA1c from baseline to 1 year was -0.4% (P<.0001). Similarly, among 141 patients who had glargine added to their existing exenatide treatment, the mean HbA1c reduction was -0.9% (P<.0001).
     The mean number of hypoglycemic events per patient increased slightly over baseline, but not significantly, reported Philip Levin, MD, from Model Clinical Research in Baltimore, Maryland, and colleagues.
     “These are some of the toughest patients [to treat] because they’re very heavy-maybe 110 kg, and what we found is that if you combine exenatide with glargine, either on glargine first and then exenatide or the reverse, either way it’s very effective in this very tough population,” said Levin in an interview.
     He and his colleagues conducted a retrospective study of real-world outcomes among patients treated with a combination of the drugs in a U.S. managed care setting from January 2006 through June 2009, using data from a U.S. national insurance claims database.
     They looked at HbA1c values and lipid levels at baseline and at 1-year follow-up in a total of 422 patients who were eligible for analysis (67% received glargine with exenatide as an add-on).
     In addition to the improvements in mean HbA1c noted above, the investigators saw improvements in lipid levels during follow-up, with significant reductions in low-density lipoprotein cholesterol in the exenatide added to glargine group (-15.2 mg/dL, P=.0003)  and reductions in triglycerides in the glargine added to exenatide group (-59.3 mg/dL, P=.0209).
     At baseline, 5% of patients on glargine added to exenatide and 5.7% of those on exenatide added to glargine had had a hypoglycemic episode (difference not significant). Through 1 year of follow-up, the respective percentages were 5.3% and 5.0% (difference between cohorts and difference from baseline not significant).
     There were, however, a significant number of dropouts, with only 11% of patients in the glargine-added cohort and 9.9% of those in the exenatide-added cohort still taking both drugs at 1 year. Approximately 44% of patients in each cohort remained on glargine at last follow-up, but only 21% in the glargine-added and 23.6% in the exenatide-added cohorts continued to take exenatide.
     “These data do not allow us to study why medication persistence was low. It could be that exenatide was not tolerated because of gastrointestinal side effects or the off-label nature of the combination use,” the authors wrote.