ADA 2009: Once-Weekly Exenatide Achieves Better Glycemic Control Than Daily Sitagliptin or Pioglitazone

Martha Kerr

June 09, 2009

June 9, 2009 (New Orleans, Louisiana) — Once-weekly treatment with the investigational agent exenatide (Byetta, Amylin Pharmaceuticals) resulted in better glycemic control than either daily sitagliptin (Januvia, Merck) or daily pioglitazone (Actos, Takeda Pharmaceuticals) for patients with type 2 diabetes who were also receiving metformin.

Results of DURATION-2, a randomized 26-week study of 491 patients with type 2 diabetes, were announced here at the American Diabetes Association (ADA) 69th Scientific Sessions by principal investigator Richard Bergenstal, MD, president-elect of the ADA and director of the International Diabetes Center in Minneapolis, Minnesota.

In DURATION-1, the researchers showed that a once-weekly formulation of exenatide exerted better glycemic control than a twice-daily formulation without increased risk for hypoglycemia.

DURATION-2 compared the efficacy, safety, and tolerability of the glucagon-like peptide inhibitor-1 (GLP-1) receptor agonist exenatide, 2 mg weekly, with 45 mg daily of the thiazolidinedione pioglitazone, and the 100 mg daily of the dipeptidyl peptidase-4 inhibitor sitagliptin. Patients were randomized to 1 of the 3 treatment groups.

Average baseline A1c was 8.5% (±1.1%), fasting plasma glucose was 164 mg/dL (±47 mg/dL), and baseline weight was 88.0 kg (±20.1 kg).

Weekly exenatide "produced a clinically and statistically superior reduction in A1c compared with either sitagliptin or pioglitazone," Dr. Bergenstal told Medscape Diabetes & Endocrinology. "Exenatide's effects could be seen as early as week 6."

"Significantly more patients on weekly exenatide therapy achieved A1c targets of 7.0% and below and 6.5% and below than with either sitagliptin or pioglitazone," he added.

A1c values of 7% or below were achieved in 66% of patients taking exenatide, 42% taking sitagliptin, and 56% taking pioglitazone (P < .05).

A1c levels of 6.5% or below were achieved in 43% of patients taking exenatide, 18% taking sitagliptin, and 33% taking pioglitazone (P < .05).

At 26 weeks, there was a drop in fasting plasma glucose of 32 mg/dL (±4 mg/dL) with exenatide, 16 mg/dL (±4 mg/dL) with sitagliptin, and 27 mg/dL (±4 mg/dL) with pioglitazone (P < .05).

There was a weight loss of 2.7 kg (±0.4 kg) with exenatide and of 0.9 kg (±0.4 kg) with sitagliptin. There was a weight gain of 3.2 kg (±0.4 kg) with pioglitazone, for a difference in weight between exenatide and pioglitazone of 5.1 kg (P < .05).

"We also saw significant improvements from baseline in systolic blood pressure, albumin-creatinine ratio, and [brain natriuretic peptide] with exenatide," Dr. Bergenstal added.

Improvements were seen with all 3 drugs in C-reactive protein and adiponectin levels.

All treatments were generally well tolerated. Nausea was the most frequently reported adverse event, occurring in 24% of patients taking exenatide, 10% taking sitagliptin, and 5% taking pioglitazone. Nausea was generally mild and transient.

There were no episodes of major hypoglycemia in the trial.

"Exenatide is an effective new drug," John Gerich, MD, professor of medicine at the University of Rochester School of Medicine and director of the Clinical Research Center's Diabetes Research Laboratory in New York, told Medscape Diabetes & Endocrinology.

"Its best feature is the weight loss that occurs with it. A drawback is that it does cause nausea, but that tends to go away over time," Dr. Gerich observed.

"Exenatide is not going to be first-line therapy, I don't think. Other drugs are clearly better, like metformin with add-on therapy with sulfonylurea and basal insulin, if needed. But I would use it as a second or third drug," Dr. Gerich said.

Dr. Bergenstal said a new drug application for exenatide has already been submitted to the US Food and Drug Administration for the once-weekly formulation, and it received a "positive indication for approval" in Europe last month.

DURATION-2 was supported by Amylin Pharmaceuticals and Eli Lilly. Dr. Bergenstal reported conflicts of interest with Amylin Pharmaceuticals, Eli Lilly, Intuity, Abbott Diabetes Care, Lifescan (a Johnson & Johnson Company), MannKind Corporation, Medtronic MiniMed, Novartis Pharmaceuticals, and Novo Nordisk. Dr. Gerich reported a financial relationship with MannKind Corporation.

American Diabetes Association (ADA) 69th Scientific Sessions: 6-LB. Presented June 7, 2009.

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