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Dulaglutide vs. Exenatide as Add-On Therapy to Pioglitazone and Metformin in T2DM

Study seems to indicate superiority of dulaglutide, a long-acting GLP-1 receptor agonist that is administered once-weekly…. 

A parallel-arm, multicenter, randomized controlled trial was conducted in patients with type 2 diabetes and a mean baseline HbA1c of 8.1% taking 1,500-3,000 mg of metformin and 30-45 mg of pioglitazone to compare the safety profile and reduction in HbA1c achieved by adding on dulaglutide 1.5 mg, dulaglutide 0.75 mg, exenatide 10 μg, or placebo. Patients were randomized to receive these add-on agents at a 2:2:2:1 ratio, respectively. The placebo-controlled treatment period only lasted 26 weeks, and the primary end point was measured at 26 weeks because this study’s primary objective was to determine whether dulaglutide 1.5 mg was superior to placebo in reducing HbA1c at 26 weeks. However, the active-controlled treatment was continued for 52 weeks.

The change established in least squares mean ± SE HbA1c from baseline to the primary end point was −1.51 ± 0.06% for dulaglutide 1.5 mg, −1.30 ± 0.06% for dulaglutide 0.75 mg, −0.99 ± 0.06% for exenatide, and −0.46 ± 0.08% for placebo. Dulaglutide was superior to placebo at both doses after 26 weeks of treatment (both adjusted one-sided p <0.001), it was superior to exenatide at both doses after 26 and 52 weeks of treatment (both adjusted one-sided p <0.001), and it reduced HbA1c to the targeted goal in a larger percentage of patients than placebo and exenatide at both doses (all p <0.001). Patients taking dulaglutide 1.5 mg had a lower number of hypoglycemia incidents, none of which were reported to be severe, than those taking exenatide. Nausea, vomiting, and diarrhea were the most common gastrointestinal side effects, and in most instances, these adverse events were mild to moderate and only temporary.

Based on the results of the data, dulaglutide proved to be superior against placebo and exenatide at achieving glycemic control at both once-weekly doses. In addition to being more efficacious, it also had a more desirable safety profile and was tolerable in patients.

Practice Pearls:

  • Dulaglutide is a GLP-1 receptor agonist dosed once-weekly to treat type 2 diabetes.
  • This study indicated that dulaglutide was superior at reducing HbA1c, while maintaining an acceptable tolerability and lower incidents of hypoglycemia, when compared to placebo and exenatide.
  • Mild to moderate nausea, vomiting, and diarrhea were the most common adverse effects caused by dulaglutide, and these side effects were usually temporary. 

Wysham C, Blevins T, Arakaki R, Colon G, Garcia P, Atisso C, Kuhstoss D, Lakshmanan M. Efficacy and Safety of Dulaglutide Added Onto Pioglitazone and Metformin Versus Exenatide in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-1). Diabetes Care; 2014 Aug; 37(8):2159-67.