medwireNews: A phase 3 cardiovascular safety trial finds exenatide delivered from an osmotic mini-pump to be noninferior to placebo.
Writing in Nature Medicine, Christian Ruff (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-researchers list several potential advantages of the medication–device combination, termed ITCA 650, over exenatide injections.
These “include maintenance of consistent blood concentration of drug and reliable daily control of blood glucose levels,” they say, along with the likelihood of more consistent use of the medication, compared with weekly injections. They note that participants in EXSCEL, the cardiovascular outcomes trial for weekly exenatide, took medication covering only about three-quarters of the treatment period.
The current trial – FREEDOM CVO – involved 4156 people with type 2 diabetes, 76% of whom had established atherosclerotic cardiovascular disease. Their median glycated hemoglobin level was 8.0% (64 mmol/mol) and median diabetes duration was approximately 10 years.
During follow-up averaging 16 months, 4.6% of the participants randomly assigned to use ITCA 650 had a primary endpoint event of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina.
This also occurred in 3.8% of the participants randomly assigned to receive placebo (also delivered from the osmotic mini-pump), meaning that ITCA 650 met the required criterion for noninferiority.
For the individual endpoints, cardiovascular death occurred in 1.3% versus 1.1% of the ITCA 650 and placebo group, respectively, myocardial infarction in a corresponding 1.8% and 1.3%, stroke in 1.1% and 1.1%, and unstable angina in 0.6% and 0.7%.
Exenatide treatment resulted in glycated hemoglobin levels that were an average 0.8 percentage points lower than those in the placebo group, and bodyweight that was an average of 4.24 kg lower. Adverse events were as expected for the glucagon-like peptide-1 receptor agonist class, with gastrointestinal events being more common with exenatide than placebo.
The researchers say that the duration and size of the trial means that no conclusions can be drawn about the potential for ITCA 650 being cardioprotective.
They observe that there was a trend toward cardioprotection in the EXSCEL trial of injectable exenatide and a significant benefit in the AMPLITUDE-O trial of efpeglenatide, which is exenatide-based.
“A larger cardiovascular outcomes trial is needed to more precisely define the cardiovascular effects of ITCA 650,” they conclude.
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