May 23, 2012 (New York, New York) — Early data from a small study testing a new glucagonlike peptide-1 (GLP-1) agonist showed the drug significantly reduced blood pressure in a group of patients with type 2 diabetes mellitus. Both doses tested in the phase 2 study met the end point of noninferiority for 24-hour mean systolic blood pressure, but only the 1.5-mg dose was superior to placebo for reducing blood pressure, report investigators.
The results of the study with the once-weekly treatment of dulaglutide (Eli Lilly, Indianapolis, IN) were presented yesterday here at the American Society of Hypertension 2012 Scientific Sessions by Dr Keith Ferdinand (Tulane University School of Medicine, New Orleans, LA). Like other GLP-1 analogs before it, including exenatide (Byetta, Amylin Pharmaceuticals) and liraglutide (Victoza, Nova Nordisk), dulaglutide is currently being tested as a potential treatment for type 2 diabetes. Previous studies, said Ferdinand, have suggested that this class of drug might be associated with small reductions in blood pressure and increases in heart rate.
In the present study, 755 patients treated with other oral antihyperglycemic medications were randomized to placebo, dulaglutide 0.75 mg, or dulaglutide 1.5 mg for 16 and 26 weeks. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM). For inclusion in the study, the mean seated clinic blood pressure for patients was >90/60 mm Hg and <140/90 mm Hg.
As expected, both doses of dulaglutide reduced HbA1c levels from baseline, and these reductions were statistically significant compared with placebo.
At 16 weeks, treatment with the 0.75-mg and 1.5-mg doses of dulaglutide reduced 24-hour mean systolic blood pressure 1.07 mm Hg and 2.79 mm Hg, respectively, and both reductions met the primary end point of noninferiority compared with placebo. At 26 weeks, the reduction in systolic blood pressure with the 0.75-mg and 1.5-mg doses was 1.71 mm Hg and 2.66 mm Hg. The reduction in systolic blood pressure with the 1.5-mg dose was statistically superior to the change observed with placebo, but the changes in diastolic pressure were not statistically significant.
Dulaglutide 1.5 mg increased the mean 24-hour heart rate 2.84 and 3.5 beats per minute when measured at 16 and 24 weeks, respectively, and these changes were statistically significant when compared with placebo. Treatment-related adverse events were similar to what has been observed with other GLP-1 agonists, including diarrhea, headache, nausea, and vomiting. Ferdinand said that the GLP-1 agonists are associated with weight loss, but the reductions in blood pressure were unrelated to weight changes in the present study.
Session moderator Dr George Bakris (University of Chicago, IL) noted that previous analyses of the VALUE data have shown that increases in heart rate were associated with increases in mortality, even when blood pressure is controlled. Ferdinand said the group is aware of the VALUE analysis, but at the present time they are unaware of the clinical significance--and do not fully understand the mechanisms--of the changes in heart rate with dulaglutide. Larger, longer phase 3 clinical trials are currently under way, he noted. These studies will also determine the clinical relevance of the blood-pressure reductions, as they will be able confirm if the blood-pressure effects correlate with long-term clinical outcomes.
Heartwire from Medscape © 2012 Medscape, LLC
Cite this: Dulaglutide Passes BP Hurdle, But Heart-Rate Increase Observed - Medscape - May 23, 2012.