The study was designed to assess the safety, tolerability and pharmacokinetics of Exenatide ( Byetta ) LAR (long-acting release ) given once a week.
After 15 weeks, both doses of Exenatide LAR were well tolerated and expected therapeutic blood levels of Exenatide were achieved.
Dose-dependent improvements in hemoglobin A1C ( A1C ) and weight were observed.
A1C, a measure of glucose control, improved approximately 2 percent for subjects receiving the high dose of Exenatide LAR, compared to placebo.
At the beginning of the study, the average A1C of study participants was approximately 8.5 percent. The decrease in A1C was progressive with no evidence of a plateau at week 15.
Twelve of the 14 high-dose subjects who entered the study with an A1C greater than 7 percent achieved an A1C of 7 percent or less at 15 weeks.
None of the 14 subjects receiving placebo achieved that target.
The American Diabetes Association recommends a target A1C of less than 7 percent.
Fasting blood glucose concentrations were reduced by approximately 50 mg/dL for subjects in the high dose group compared to those receiving placebo. Subjects in this group experienced an average weight reduction of approximately 9 pounds compared to those receiving placebo.
The most common adverse event was mild nausea, which occurred in approximately 20 percent of subjects in the high dose group compared to approximately 7 percent in the placebo group.
No severe gastrointestinal side effects were reported. No severe hypoglycemia was reported, and no subjects receiving exenatide LAR withdrew because of adverse events.
This Phase 2, randomized, placebo-controlled, double-blind study includes 45 subjects with type 2 diabetes who were not achieving adequate glucose control using diet and exercise with or without Metformin.
Subjects were randomized to receive 15 once-weekly subcutaneous injections of Exenatide LAR at one of two doses or placebo. At this time, study participants have completed the active dosing period. Subjects will be observed for an additional 12 weeks with follow-up observations and data analyses ongoing.
On April 28, 2005, the Food and Drug Administration ( FDA ) approved twice daily Exenatide under the trade name Byetta injection for use by people with type 2 diabetes who are unsuccessful at controlling their blood sugar levels despite using commonly prescribed oral medications metformin, a sulfonylurea, or both.
Amylin, Lilly, and Alkermes are working together to develop a sustained release, subcutaneous injection of Exenatide for the treatment of type 2 diabetes.
Byetta is the first in a new class of drugs for the treatment of type 2 diabetes called incretin mimetics and exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 ( GLP-1 ).
GLP-1, secreted in response to food intake, has multiple effects on the intestine, liver, pancreas and brain that work in concert to improve blood sugar.
Byetta injection improves blood sugar control in patients with type 2 diabetes who are taking Metformin, a sulfonylurea, or both.
Byetta is not a substitute for insulin in patients whose diabetes requires insulin treatment.
Byetta is not recommended for use in patients with severe problems digesting food or those who have severe disease of the stomach or kidney.
Byetta has not been studied in children or pregnant women.
When Byetta is used with a medicine that contains a sulfonylurea, hypoglycemia is a possible side effect. To reduce this possibility, the dose of sulfonylurea medicine may need to be reduced while using Byetta.
Other common side effects with Byetta include nausea, vomiting, diarrhea, dizziness, headache, feeling jittery, and acid stomach. Nausea is most common when first starting Byetta, but decreases over time in most patients.
Byetta may reduce appetite, the amount of food eaten, and body weight. No changes in dose are needed for these side effects.
Source: Eli Lilly, 2005