Patients with type 2 diabetes treated for 84 weeks with injected extended-release once-weekly exenatide (Bydureon; Amylin Pharmaceuticals, Lilly, and Alkermes) demonstrated superior ongoing glycemic control, sustained overall weight loss, and a lower risk for hypoglycemia than patients treated with insulin glargine, according to new data from the DURATION-3 trial.
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 here at the American Diabetes Association 71st Scientific Sessions.
"This 84-week planned interim analysis confirmed the observations of the core study, and demonstrated that once-weekly exenatide improved glycemic control in patients who no longer had good control on oral agents, with a low risk of hypoglycemia and a mean decrease in weight," Dr. Diamant reported.
Exenatide for extended-release injectable suspension is approved in the European Union and is under regulatory review in the United States.
The DURATION-3 study showed that at 84 weeks, patients treated with exenatide experienced a significantly greater glycosylated hemoglobin (HbA1c) reduction from baseline, sustained weight loss, and a lower risk for hypoglycemia than patients treated with insulin glargine. HbA1c was reduced by 1.2% with exenatide and by 1.0% with insulin glargine, Dr. Diamant explained.
Significantly more patients achieved an HbA1C of 6.5% or less with exenatide. In addition, patients on exenatide lost an average of 4.5 pounds, whereas those on insulin glargine gained an average of 5.3 pounds, for a difference of 9.8 pounds between treatment groups.
"This study shows that once-weekly exenatide is safe and efficacious for a prolonged period of time (84 weeks) in the treatment of patients with type 2 diabetes mellitus who failed on oral therapy," Dr. Diamant told Medscape Medical News. "The study will continue up to 2.5 years," she added.
Dr. Diamant noted that the drug has recently been approved in Europe and the agent can now be prescribed there. "As for other regions, including the United States, these data can be added to the portfolio of data on once-weekly exenatide to support US Food and Drug Administration approval; the agent appears to be safe and effective," she said.
"More time is needed to evaluate the true added value of exenatide and other agents in the incretin class, in terms of effectiveness in maintaining glycemic control in type 2 diabetes mellitus, potentially for a longer period of time than the conventional agents, due to beta cell preservation," she said.
"In addition, long-term effects such as malignancy, pancreatitis, and hitherto unknown side effects should be addressed in large outcome trials. This will be done in the Exenatide Study of Cardiovascular Event-Lowering (EXSCEL) trial."
Results from the 3-year DURATION-1 confirmed the findings of DURATION-3 in terms of HbA1c lowering and weight loss. Patients treated with once-weekly exenatide also experienced improvements from baseline in several cardiometabolic risk markers, including systolic blood pressure (–2.1 mm Hg), total cholesterol (–9.9 mg/dL), low-density-lipoprotein cholesterol (–7.0 mg/dL), and triglycerides (–12%).
Once-Monthly Exenatide Shows Promise
Results from a phase 2 study of an investigational once-monthly injectable suspension formulation of exenatide also improved glycemic control, including reductions in HbA1c and fasting plasma glucose and modest weight loss. These findings were presented here in a late-breaking poster session.
The study involved 121 patients who received 1 of 3 different doses (5 mg, 8 mg, and 11 mg) of once-monthly exenatide. After 20 weeks of treatment (5 injections), patients receiving once-monthly exenatide experienced average improvements in HbA1c from baseline of 1.3% for the 5 mg and 8 mg doses, and 1.5% for the 11 mg dose. Likewise, reductions in fasting plasma glucose ranged from 25 mg/dL to 49 mg/dL in a dose-dependent manner.
In addition, 50% of those treated with the 5 mg dose, 57% treated with the 8 mg dose, and 70% treated with the 11 mg dose achieved an HbA1c below 7%. Weight loss with the 3 doses ranged from 0.9 to 2.4 pounds.
Compared with once-weekly exenatide used in a reference group, results for HbA1c, fasting glucose, and weight in the once-monthly exenatide groups were generally comparable.
"New treatment regimens and therapies add choices for providers struggling with the complexities of this disease," said Donna Rice, MBA, RN, CDE, from the Baylor Health Care System in Houston, Texas, when asked to comment on these studies. "Individualizing therapy will only enhance compliance and outcomes," she toldMedscape Medical News.
"As an educator, my goal is to simplify diabetes for my patients and make their treatment plan work for them," she said. "A once-weekly treatment can be a great alternative to maximize control for many patients without risking hypoglycemia, and individualized care is the best way to enhance outcomes," she said.
Dr. Diamant reports being a consultant for Eli Lilly and Company, Merck, Novo Nordisk, and Sanofi-Aventis; receiving research support from Amylin Pharmaceuticals, Eli Lilly and Company, Merck, Novartis, Novo Nordisk, and Takeda Pharmaceuticals International; and being on the speaker's bureau for Eli Lilly and Company, Merck, and Novo Nordisk. Ms. Rice has disclosed no relevant financial relationships.
American Diabetes Association (ADA) 71st Scientific Sessions: Abstracts 0277-OR (DURATION-3) and 969-P (DURATION-1), presented June 25, 2011; abstract 0046-LB, presented June 27, 2011.
此外，也應以更大型的試驗評估惡性腫瘤、胰臟炎、以及迄今未知的副作用等長期影響，這正是「Exenatide Study of Cardiovascular Event-Lowering (EXSCEL)」試驗在進行的。
DURATION-1試驗的3年結果確認了DURATION-3試驗在HbA1c與減輕體重方面的結果；每週使用1次exenatide治療的病患在諸多心臟代謝風險方面也比開始時有所改善，包括收縮壓(–2.1 mm Hg)、總膽固醇 (–9.9 mg/dL)、低密度脂蛋白膽固醇(–7.0 mg/dL)與三酸甘油脂(–12%)。
該研究包括了121名病患，每月使用1次、接受3種不同exenatide劑量(5 mg、8 mg和11 mg)之一，治療20週(注射5次)之後，每月使用1次exenatide的病患，其HbA1c 比開始時改善了1.3%(5 mg和8 mg組)，以及11 mg組的1.5%；另外，空腹血漿血糖值也與劑量有關，降低範圍介於25 mg/dL- 49 mg/dL。
此外，5 mg、8 mg和11 mg 組分別有50%、57%和70%達到HbA1c小於7%，這3組的體重降低範圍介於0.9- 2.4磅(約0.4-1.1公斤)。