In order to increase compliance and improve efficacy, there is an experimental long acting exenatide once monthly injectable suspension in the pipeline. This long acting formulation is currently in phase-2 trial and has showed promising results in controlling A1C in type 2 diabetes patients….
Michaela Diamant, MD, PhD, associate professor of endocrinology and scientific director of the Diabetes Center, VU University Medical Center, in Amsterdam, the Netherlands, presented the findings. The study was done on 121 subjects to assess the efficacy, safety and tolerability of long acting once-monthly exenatide for 20 weeks. Subjects were randomized to be given 2 mg weekly subcutaneous injection of exenatide or once monthly 5 mg, 8 mg or 11 mg of exenatide. Based on phase-2 study results, subjects receiving long acting exenatide had an average improvement in A1C from baseline on 1.3 percentage points for the 5 mg and 8 mg dose and 1.5 percentage points for 11 mg dose.
About 50 to 70% of subjects achieved the ADA recommended A1C goal of less than 7. Fasting plasma glucose was reduced by 25 mg/dl with the 5 mg dose, 20 mg/dl with the 8 mg dose, and 49 mg/dl with 11 mg dose. There was also a modest amount of weight loss using once-monthly exenatide. There were a high number of subjects who completed the phase-2 trial of once-monthly exenatide. The most common adverse events associated with long acting exenatide were headache (17-27%) and nausea (17-23%). The pharmacokinetic profile of all doses of long acting exenatide has resulted in known steady state exenatide plasma level.
The phase-2 trial on long acting once monthly exenatide has shown promising results in achieving A1C goal in type-2 diabetes patients and can be a viable option in patients with a poor history of compliance.
The Duration-1 study was done on 295 patients to compare the efficacy of Bydureon (once-weekly exenatide) to Byetta and was followed by an open-ended extension period in which all subjects either continued treatment with Bydureon or switched from Byetta to Bydureon.
About 64% (n=194) subjects finished three years of treatment, 57% of whom achieved an A1C goal of less than 7.
Data from Duration-1 trial showed that after three years of study, subjects receiving once-weekly exenatide experienced a large reduction in A1C (1.6% points) and weight (5.1 lb) compared to baseline. Subjects also experienced improvements in systolic blood pressure (-2.1 mmHg), total cholesterol (-9.9 mg/dl), LDL(-7.0 mg/dl) and triglycerides (-12%).
Three hundred ninety subjects were enrolled in the Duration-3 study and received either Bydureon or Lantus for 26 weeks: 173 subjects in each treatment group followed 84 weeks extension. Similar data was achieved from the Duration-3 trial, in which once weekly exenatide was compared with Lantus. There was a significant reduction of A1C (1.2% points from baseline), weight loss (4.5 lb) and a lower risk of hypoglycemia. A similar proportion of patients achieved an A1C goal of less than 7 in both treatment groups.
The results from the Duration-1 trial, showed no significant risk of increase in QT interval with once-weekly extended release exenatide. The change in QT interval prolongation was small and clinically insignificant at 14 weeks (1.7 msec) and 30 weeks (3.0 msec). Based on results, there was no co-relation between increase in QT interval and blood plasma concentration of blood plasma and renal status. Hopefully the FDA will look at this data and give a thumbs-up to approval.
Summarized by Pinang Balsara, PharmD Candidate, LECOM College of Pharmacy