Once-weekly exenatide improved glucose control, weight loss in DURATION studies
ADA 70th Scientific Sessions
ORLANDO — A once-weekly injection of exenatide may be an important therapeutic option for patients with type 2 diabetes for whom weight loss and hypoglycemia are particular concerns, Michaela Diamant, MD, said at the Joint ADA/The Lancet Symposium here.
Diamant, of VU University Medical Center, Amsterdam, presented the 26-week results of DURATION-3. The study compared investigational, once-weekly, extended-release exenatide injection (2 mg; Bydureon, Eli Lilly, Amylin and Alkermes) with insulin glargine titrated to target in 456 adults with poorly controlled type 2 diabetes despite use of maximum tolerated doses of glucose-lowering drugs for at least 3 months.
Change in HbA1c at 26 weeks, the study’s primary endpoint, was greater among patents assigned to once-weekly exenatide, with a decrease of –1.5% vs. –1.3% with insulin glargine (P=17). Exenatide was further associated with a mean weight loss of –2.6 kg per patient whereas insulin glargine produced a mean weight gain of 1.4 kg per patient (P<.0001).
Fourteen of the 456 adults enrolled in the study discontinued participation because of adverse events (12 assigned exenatide). Gastrointestinal events were more frequently reported with exenatide; however, rates of hypoglycemia were lower with exenatide vs. insulin glargine. There was a small but significant increase in mean heart rate with exenatide treatment; however, the researchers said the clinical significance is unclear.
Results of the study “would be strengthened by replication in other populations,” the researchers said. Most patients included in DURATION-3 were white.
A planned extension of DURATION-3 out to 2.5 years is in progress to monitor long-term outcomes of these treatment strategies.
Results of the DURATION-2 study also demonstrated improved glucose control and weight loss with once-weekly exenatide, but in comparison with daily sitagliptin 100 mg (Januvia, Merck) and pioglitazone (Actos, Takeda), according to Richard M. Bergenstal, MD, of the International Diabetes Center at Park Nicollet, Minneapolis, Minn.
Treatment with exenatide reduced HbA1c by –1.5% vs. –0.9% in the sitagliptin group and –1.2% in the pioglitazone group. Patients in the exenatide group lost a mean 2.3 kg vs. 0.8 kg in the sitagliptin group and a mean weight gain of 2.8 kg in the pioglitazone group.
No major episodes of hypoglycemia occurred in any group. Nausea was reported in 24% of the exenatide group and 10% of the sitagliptin group, and diarrhea in 18% of the exenatide group and 10% of the sitagliptin group. Upper respiratory infection (10%) and peripheral edema (8%) were the most frequently reported events with pioglitazone.
“Currently, there is more promise, few disadvantages and some unknowns about treatment with long-acting exenatide for diabetes,” Anoop Misra, MD, of Fortis Hospital, New Delhi, India, and Shashank Joshi Lilavati, MD, of Bhatia Hospital, Mumbai, India, wrote in an editorial accompanying the DURATION-3 study published in The Lancet.
“Despite advances in antihyperglycemic therapy, a drug which would lead to substantial prevention of macrovascular and microvascular complications, decreases mortality and is convenient and affordable, remains the undiscovered Holy Grail of diabetes management,” the editorialists wrote. – by Katie Kalvaitis
The studies being reported at the ADA comparing glucagon-like peptide 1 agonists with dipeptidyl peptidase-4 inhibitors are neither a surprise nor do they change the 'landscape' with respect to choice of therapeutic agents. Firstly, the GLP-1 agonists are all proteins, which must be given by injection either twice a day (exenatide), once per day (liraglutide) or once a week (exenatide, taspoglutide). The GLP-1 agonists are very potent agents and they have an excellent safety profile with respect to hypoglycemia.; however, they have a very high rate of gastrointestinal side effects, including nausea and vomiting. This has led to many patients having to discontinue the agents. The GLP-1 agonists also have excellent properties with regard to weight loss. They are an important part of the therapeutic armamentarium. There is the assumption that use of once-daily or once-weekly injection of a GLP-1 agonist would result in improved patient acceptance and compliance. However, it remains to be seen whether the presumed advantage of less frequent injections would overcome the 'injection barrier' and cause patients to prefer this mode of therapy relative to an oral agent or in combination of oral agents.
– Helena W. Rodbard, MD
Medical Director, Endocrine and Metabolic Consultants, Rockville, Md.
For more information:
- Bergenstal RM. Joint ADA/The Lancet Symposium.
- Diamant M. Joint ADA/The Lancet Symposium. Presented at: American Diabetes Association 70th Scientific Sessions; June 25-29, 2010; Orlando.
- Diamant M. Lancet. 2010;375:2234-2253.