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Astrazeneca announces new tolerability data for exenatide once weekly in patients with type 2 diabetes

AstraZeneca has announced new analyses of exenatide once weekly (ExQW) demonstrating a favorable gastrointestinal (GI) tolerability profile, including less frequent upper and lower GI adverse events (AE), compared to shorter-acting glucagon-like peptide-1 receptor agonists (GLP-1RA), exenatide twice daily (ExBID) and liraglutide once daily (LiraQD).1 These results were presented today at the 51st Annual Meeting of the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden.

To evaluate differences in GI tolerability with short- and long-acting GLP-1RAs, intent-to-treat (ITT) analyses were conducted, using pooled data from three studies comparing ExQW (n=617) to ExBID (n=606) and, separately, data from DURATION-6, which compared ExQW (n=461) to LiraQD (n=450). Investigators also explored whether GI AEs were associated with differences in HbA1c or weight reductions.

In the pooled analysis of three Bydureon clinical trials, ExQW was associated with lower rates of upper GI AEs such as nausea and vomiting (24%) compared to ExBID (37%). Separate analysis of DURATION-6 also demonstrated that ExQW was associated with lower rates of upper GI AEs at 17% compared to 33% for LiraQD (P<0.001 vs longer-acting). Similarly, the percentage of patients treated with ExQW who experienced a combination of upper and lower AEs was less (7%) compared to LiraQD (14%), P<0.001 vs longer-acting. While few patients stopped treatment because of a GI AE, discontinuation was more frequent with the shorter-acting ExBID (6%) and LiraQD (4%), respectively compared to ExQW (1%) in both analyses (P<0.05).1

“The availability of GLP-1RA agonists is an important addition to treatment options for patients with type 2 diabetes. However, some patients may be unable to tolerate them because of adverse gastrointestinal effects,” said Michael Horowitz, MD, lead study investigator and Director of the Endocrine and Metabolic Unit at the Royal Adelaide Hospital, Australia. “Our analysis of the adverse event profiles of short- and long-acting GLP-1 agonists demonstrated that exenatide once weekly has a favorable GI tolerability profile and lower rates of discontinuation compared to daily agents, which may support patients in remaining adherent to achieve clinically meaningful treatment benefits.”

Data was also presented from a real-world evidence study assessing German health insurance claims and adherence rates for patients initiating GLP-1RA therapy with ExQW (n=5,449) and LiraQD (n=24,648). Adherence was measured over a six-month period by calculating the ‘proportion of days covered’ (PDC) and demonstrated that the median PDC was 0.88 for ExQW and 0.77 for LiraQD (P<0.001). Overall, 53.4% of patients receiving ExQW, and 47.7% of those receiving LiraQD had an adherence rate of at least 80% (P<0.001) during the six months post-initiation of treatment.2

A separate post-hoc analysis of pooled data (n=329) from extensions (2.5-3 years) of three trials (DURATION-1, -2, -3) showed that after three years, patients receiving ExQW experienced significant reductions in mean HbA1c (-1.06%) and fasting glucose (1.7 mmol/L) from baseline. These patients also achieved reductions in body weight (-2.4 kg).2 The effect on weight is not currently an approved indication for treatment with ExQW.

“Given variations in dosing frequency across GLP-1 agents, it is important that physicians understand the differences between daily and weekly options,” said Elisabeth Bj√∂rk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca. “These data strengthen support behind exenatide once weekly on key factors that can potentially impact patient outcomes and quality of life.”