In this randomized study, 69 people with type 2 diabetes who were treated with exenatide (5 mcg BID for 4 weeks and 10 mcg BID to 20 mcg TID (20 mcg TID is a currently unapproved dosage of the marketed formulation of exenatide, BYETTA(R) (exenatide) injection) for the remainder of the year) or insulin glargine (both with metformin) were compared on measures of beta-cell function, blood sugar control and weight change after one year (52-weeks) of treatment.

In this study, people with type 2 diabetes who used exenatide for one year, compared to those treated with insulin glargine, showed significant improvements in beta-cell function as measured by arginine and glucose induced C-peptide (a peptide associated with insulin production) secretion during a glucose clamp procedure (a technique used to assess insulin secretion)(2,3). Specifically, C-peptide secretion in response to arginine administration (which produces maximal beta-cell stimulation) was 146 percent greater after one year of treatment with exenatide when compared to insulin glargine (mean ratio relative to baseline for exenatide and insulin glargine + or -SEM: 3.19 + or - 0.24 vs. 1.31 + or - 0.07, respectively, p<0.0001). First phase glucose induced C-peptide secretion was 52 percent greater after one year of exenatide compared to insulin glargine therapy (mean ratio relative to baseline + or -SEM: 1.75 + or - 0.10 vs. 1.16 + or - 0.06, respectively, p<0.0001). Second phase C-peptide secretion increased 185 percent more with exenatide (mean ratio relative to baseline + or -SEM: 3.05 + or - 0.22) versus insulin glargine (1.08 + or - 0.05, p<0.0001).

The average HbA1c of randomized patients at the start of the trial was 7.5 + or - 0.1 percent. Treatment with exenatide resulted in blood sugar control (as measured by reductions in HbA1c) comparable to treatment with insulin glargine (-0.8 + or - 0.1 percent and -0.7 + or - 0.2 percent, respectively, a difference between groups that was not statistically significant).

On average, exenatide treatment also resulted in a reduction in body weight. At the start of the study, randomized patients had a mean weight of 91.4 + or - 1.6 kg (201.6 + or - 3.5 lb). Patients on exenatide lost an average of 3.6 + or - 0.6 kg (7.8 + or - 1.4 lb), while those receiving insulin glargine gained an average of 1.0 + or - 0.8 kg (2.2 + or - 1.8 lb). The total difference in weight between the exenatide and insulin glargine groups was 4.6 kg (10.0 lb).

"Previous exenatide studies have shown comparable glycemic improvements when compared to insulin glargine, as well as improved beta-cell function that has only been associated with exenatide treatment," said Michaela Diamant, M.D., Ph.D., Associate Professor of Endocrinology, Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands, and an author of the study. "This study lends further support to past findings and showed that adding exenatide significantly improved beta-cell function as measured by both glucose and arginine induced insulin secretion."

The side effects associated with exenatide treatment were consistent with those seen in previous studies. In clinical trials, the most common side effect is nausea, most of which is mild to moderate, affecting approximately half of patients and usually decreasing over time. Exenatide-treated patients had a lower incidence of hypoglycemia compared to insulin glargine-treated patients (8.3 percent vs. 24.2 percent, respectively).