Results from a study indicate that Exenatide injection ( Byetta ) improves blood glucose levels as effectively as Insulin Glargine ( Lantus ) for patients with type 2 diabetes failing to achieve acceptable blood gluocse control on both Metformin and a sulfonylurea, two common oral diabetes medications.
Both treatments were effective in lowering blood glucose, and patients taking Exenatide experienced weight reductions while those on Insulin Glargine gained weight.
Byetta is the first in a new class of medicines known as incretin mimetics, and was approved by the Food and Drug Administration ( FDA ) on April 28, 2005 for the treatment of type 2 diabetes.
In this study, patients in each treatment group -- either Byetta or Insulin Glargine -- lowered their average blood glucose levels, as measured by hemoglobin A1C ( A1C ), by approximately 1 percent from baseline after six months of therapy.
A1C measures a person's average glucose level over a three-month period and is often used by healthcare providers to assess blood glucose management. The American Diabetes Association ( ADA ) recommends a target A1C of less than 7 percent. Approximately half of the patients in each treatment group achieved an A1C of 7 percent or less.
The study also showed that patients on Byetta lost an average of five pounds, while patients on Insulin Glargine gained an average of four pounds.
Weight gain is a common side effect of Insulin therapy.
In addition, Byetta reduced peak glucose levels after meals better than Insulin Glargine.
In contrast, Insulin Glargine was associated with lower fasting glucose levels.
Both the Byetta and Insulin Glargine groups had similar rates of symptomatic hypoglycemia.
Patients in both treatment groups continued their oral therapy as well, which included a sulfonylurea, a therapy known to cause hypoglycemia when used alone.
" This is the first comparator study in which a non-insulin treatment for diabetes has demonstrated similar blood glucose control to Insulin for patients who are failing to achieve treatment targets on oral medications," said Robert Heine, Director of the Diabetes Center, VU University Medical Center in the Netherlands, and a lead author of the study. " When considering the weight loss and achieved glucose control, the results of this study demonstrate that Byetta can be an effective tool for the management of type 2 diabetes patients who cannot control their blood sugar using oral medications."
The primary objective of the study was to determine whether comparable glycemic control can be achieved in both groups, as evaluated by a change in A1C levels from baseline.
Additional endpoints of the study included effects on weight, postprandial glucose excursions and incidence of hypoglycemia.
- At the end of the study, both treatment groups had achieved similar A1C reductions. Byetta lowered A1C 1.0 percent while Insulin Glargine lowered A1C 1.1 percent.
- Forty-six percent of patients in the Byetta group achieved the target A1C level less than or equal to 7 percent compared to 48 percent in the Insulin Glargine group.
- When measured against the American Association of Clinical Endocrinologist recommended target A1C of less than or equal to 6.5 percent, 31 percent of patients in the Byetta group achieved this level compared to 24 percent in the Insulin Glargine group.
- Weight loss in the Byetta arm: patients using Byetta showed an average weight reduction of 2.3 kg ( 5.1 pounds ).
- Weight gain in the Insulin Glargine arm: on average, patients using Insulin Glargine gained 1.8 kg ( 4.0 pounds ).
Postprandial excursions ( post-meal blood glucose levels ):
- As measured by seven-point glucose monitoring, Byetta reduced postprandial excursions ( post-meal blood glucose levels ) following breakfast and dinner. In contrast, Insulin Glargine predominantly reduced fasting glucose ( at least eight hours after a meal ).
- Rates of symptomatic hypoglycemia were similar between treatment groups.
The most common adverse event for Byetta was nausea ( 57 percent ), which was generally mild-to-moderate and tended to decrease in frequency and severity over time.
Six percent of Byetta treated subjects discontinued due to nausea.
More than 500 patients were involved in the 26-week, multi-center, open- label, randomized, two-arm, parallel trial. The trial was designed to determine if Byetta can be used safely and effectively in combination with Metformin plus a sulfonylurea as an alternative to Insulin Glargine for type 2 diabetes patients.
Patients were randomized into two arms.
One arm received a fixed dose of Byetta ( 5 micrograms twice-a-day for first four weeks, 10 micrograms twice-a- day for remainder of study, n=283 ) in conjunction with Metformin and a sulfonylurea.
The second arm received Insulin Glargine once daily beginning at 10 insulin units per day ( n=268 ) in conjunction with Metformin and a sulfonylurea.
The Glargine dose was titrated based on finger-stick blood glucose monitoring to achieve a pre-specified target fasting blood glucose level.
Because of the fixed dosing of Byetta, patients in that arm required no dose titration or additional finger-stick testing.
The A1C baselines for the two groups were 8.2 plus or minus 1.0 percent for Byetta and 8.3 plus or minus 1.0 percent for Insulin Glargine.
Exenatide 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 stomach, liver, pancreas and brain that work in concert to regulate blood glucose.
Adverse events associated with Byetta are generally mild to moderate in intensity.
In clinical trials, the most frequently reported adverse event was mild-to-moderate, dose-dependent nausea. With continued therapy, the frequency and severity of nausea decreased over time in most patients.
Patients receiving Byetta in combination with a sulfonylurea may be at a higher risk of hypoglycemia.
To reduce this risk, lowering the sulfonylurea dosage may be considered.
Treatment with Byetta may lead to a reduction in appetite, food intake, and/or body weight, and that there is no need to modify the dosing regimen due to such effects.
Byetta is not a substitute for insulin in insulin-requiring patients.
Byetta should not be used in patients with type 1 diabetes.
Use of Byetta is not recommended in patients with end-stage renal disease or severe renal impairment, or in patients with severe gastrointestinal disease.
Byetta should be used with caution in patients receiving oral medications that require rapid gastrointestinal absorption.
Source: American Diabetes Association's ( ADA ) 65th Scientific Sessions, 2005