Exenatide Can Be Added to Single Oral Therapy in Type 2 Diabetes

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This article originally posted 12 June, 2007 and appeared in Issue 368

Exenatide can be an alternative to insulin glargine as an add-on treatment in patients with type 2 diabetes who are already receiving single-agent oral therapy, as presented as new research.

A randomized, 2-period, open-label, crossover study of 114 patients compared the effects of exenatide (5 ug), given twice a day for 4 weeks, followed by a dose of 10 ug given twice daily for 12 weeks to insulin glargine, given once daily and titrated to fasting blood glucose levels less than or equal to 100mg/dL (5.6 mmol/L). Patients continued single-agent oral therapy at the maximal dose.

Results of the study, indicate that patients with type 2 diabetes have another option outside of insulin to achieve good glycemic control, said Michael Trautmann, MD, PhD, the study's lead investigator and a medical fellow with Eli Lilly Inc.

Dr. Trautmann feels that, "It's an effective alternative to starting insulin in patients with type 2 diabetes. "We can say that these patients are candidates for starting insulin or exenatide."

Because beta-cell function worsens over time in type 2 diabetes, it is important to offer patients several possible therapies, Dr. Trautmann said.

"This is why drugs work for a number of years, and then they are no longer effective because the disease is worsening," he said. "This is why after having tried diet and exercise, one oral agent is added to the regimen. Often a second oral agent is added. Typically, insulin is the last resort when all the other options are exhausted."

Dr. Trautmann added that patients might have contraindications to metformin or sulfonylurea.

Exenatide or insulin glargine was added to ongoing monotherapy with metformin in 56% of patients and sulfonylurea in the remaining patients in two 16-week treatment periods. In terms of baseline characteristics, patients were a mean age of 54 years, mean weight was 86 kg, mean HbA1C level was 8.9%, and the mean fasting blood glucose level was (217mg/dL)12.09 mmol/L.

Investigators witnessed similar decreases in HbA1C from baseline in patients receiving exenatide vs those receiving insulin glargine: –1.43 and –1.41, respectively. Comparable proportions of patients achieved target HbA1C levels, 7% or less, with 40% of patients receiving exenatide achieving that level and 41% of those receiving insulin glargine achieving it. Further reductions in HbA1C level to 6.5% and below were achieved by 24% of patients receiving exenatide and 14% of those treated with insulin glargine, a difference that approached statistical significance (P = .056), stressed Dr. Trautmann. Both therapies maintained decreased HbA1C in the first and second treatment intervals.

Weight loss that occurred with exenatide was offset by weight gain that occurred when insulin was administered in the subsequent treatment period. Conversely, weight gain occurred when insulin was the initial treatment, and that weight was lost when exenatide treatment followed. The change in weight from baseline was significantly different (P < .001) between exenatide (–1.95 kg) and insulin glargine (+0.35 kg).

The combined 2-hour glucose excursions after breakfast, lunch, and dinner were significantly reduced in patients receiving exenatide compared with those treated with insulin (P = .036).

The incidence of nausea was 33.0% during exenatide treatment, and the incidence of headache was 8.7% during insulin therapy.

Dr. Trautmann said that one of the advantages in using exenatide is that patients do not have to adjust the dose of the medication, relative to their HbA1c levels.

"Exenatide is given before the morning and evening meal at a fixed dose," Dr. Trautmann said. "Insulin is given once daily, often at bedtime, but it can be given at anytime of day. However, it needs to be titrated. "Consequently, it is much more cumbersome to arrive at an optimal dose for insulin because one needs to test himself," said Dr. Trautmann. "You increase the insulin dose as long as hypoglycemia doesn't develop and then cut back if it does develop."

Daniel Drucker, MD, an endocrinologist at the Samuel Lunenfeld Research Institute/Mount Sinai Hospital and director of the Banting and Best Diabetes Center at the University of Toronto in Ontario, Canada, said the research demonstrates another treatment option for patients.

"There are now multiple studies that have compared exenatide to insulin," said Dr. Drucker, a professor of medicine in the division of endocrinology at the University of Toronto. "They all seem to show that there is fairly equivalent glucose control and the amount of hypoglycemia is the same. Weight ends up being a bit lower with exenatide and a bit higher with insulin. This isn't saying one drug is better than another. It gives physicians and patients more options, which is a good thing."

Dr. Drucker described insulin as the gold standard therapy, but noted that exenatide is attractive in terms of patients avoiding the need to adjust the dose of medication.

Endo 2007 Annual Meeting: Abstract OR28-5. Presented June 3, 2007.

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FACT:

Acumplia review will be announced this week. Sanofi-Aventis, the French pharmaceutical company seeks Food and Drug Administration approval of Acomplia, a drug approved in Europe for fighting obesity. The FDA is set to release its Acomplia review ahead of a Wednesday meeting at which outside experts will vote on whether it should be approved. The agency does not have to follow the experts' vote, though it often does. The drug is considered a potential blockbuster despite hitting several regulatory bumps."With the initial demand for Acomplia likely to be massive, the known neuropsychiatric side effects may make it difficult for the FDA to see a positive risk-benefit ratio. In recent weeks, the FDA has been widely criticized over a lag in getting new safety data about a GlaxoSmithKline diabetes drug to the public. Analysts say that controversy might give regulators pause at approving a new drug with potentially dangerous side effects. Studies of Acomplia have shown instances of depression, insomnia and anxiety in patients who take it. If approved in the U.S., Sanofi said it would market the drug under the name Zimulti, because FDA reviewers felt the name Acomplia could potentially mislead consumers.