Weekly exenatide improves a variety of cardiometabolic measures in patients with type 2 diabetes

June 8, 2009

A once-weekly dose of exenatide significantly improves a variety of cardiometabolic risk factors common among patients with type 2 diabetes, according to results of an extension of the DURATION-1 trial.

A once-weekly dose of exenatide significantly improves a variety ofcardiometabolic risk factors common among patients with type 2 diabetes, accordingto results of an extension of the DURATION-1 trial. "Type 2 diabetes is not just aglucocentric condition. Hypertension, obesity, dyslipidemia is so common and soimportant in this syndrome, it should be considered in the overall picture becausethey increase risk of cardiovascular disease and nonalcoholic fatty liver disease,"says Richard Bergenstal, MD, executive director, International Diabetes Center atPark Nicollet, Minneapolis, MN.

Dr. Bergenstal evaluated the cardiometabolic profile of 148 patients whocontinued once-weekly exenatide injections for an additional 22 weeks after a30-week, controlled, open-label trial of once-weekly injections. During the initial30 weeks, patients lost weight, exhibited improved glycemic control, and hadimproved markers of cardiovascular risk.

Patients completing the trial extension for a total of one year of weekly exenatidetherapy had type 2 diabetes with an average duration of 7 years, a mean age of 56,mean baseline body mass index of 35.2 kg/m², and a mean baseline hemoglobinA1c (HbA1c) of 8.3%. Average blood pressure was 130/80 mmHg onstudy entry.

"At 52 weeks, 77% of patients actually lost weight and improved theirHbA1c. There was a dramatic reduction in HbA1c of 2.0%, with adecrease in fasting blood glucose of 47 mg/dL and a mean weight loss of 4.1 kg," Dr.Bergenstal says.

In addition, there was an overall 6.2 mmHg reduction in systolic blood pressureand a greater than 11.4% decrease among patients who had abnormal systolic pressureat baseline. Patients with abnormal systolic and diastolic blood pressure atbaseline had a 10.7 mmHg decrease during the trial. Similarly, mean reduction indiastolic blood pressure was 2.8 mmHg, with patients having abnormal baselinediastolic pressure exhibiting a 3.6 mmHg reduction.

Patients also experienced a mean reduction in total cholesterol of 9.6 mg/dL anda 3.4 mg/dL mean reduction in low-density lipoprotein (LDL). Triglycerides were reduced by15% to 27%.

"There was not a significant correlation between weight change and systolic bloodpressure or change in triglycerides," Dr. Bergenstal says. However, weight loss wasmoderately correlated with reductions in diastolic blood pressure, totalcholesterol, and LDL.

Researchers also found that alanine aminotransferase (ALT) levels were reduced bya mean of 7.5 IU/L in patients with normal baseline ALT levels and by 12.0 IU.L inthose with abnormal baseline levels.

"These improvements are encouraging, and longer cardiovascular risk studies areneeded. The degree of these improvements may have a clinically important impact onpatients with type 2 diabetes and cardiovascular disease risk factors," Dr.Bergenstal says.