Results from the phase 3 AWARD-11 trial evaluating higher doses of dulaglutide showed superior HbA1c and body weight reductions with an investigational 4.5mg dose in patients with type 2 diabetes (T2D) compared with dulaglutide 1.5mg.

The randomized, double-blind, parallel-arm trial evaluated the efficacy and safety of 3mg and 4.5mg doses of dulaglutide compared with dulaglutide 1.5mg in 1842 adult patients with T2D who were inadequately controlled on metformin. Patients were randomized 1:1:1 to dulaglutide 1.5 mg (n=612), 3 mg (n=616), or 4.5 mg (n=614) once-weekly. The primary end point was the change in HbA1c from baseline to week 36. Key secondary end points included the change in body weight and the proportion of patients achieving HbA1c <7% at week 36.

Findings from the trial showed that the 4.5mg dose met the primary end point achieving superior HbA1c reductions compared with dulaglutide 1.5mg using 2 statistical approaches – efficacy estimand (used to evaluate results in patients who stayed on treatment and did not start another diabetes drug throughout the trial) and treatment-regimen estimand (includes data from all patients through the end of the trial, which may include confounding effects of rescue medication or discontinuation from the study drug or trial). 

Based on the efficacy estimand, dulaglutide 4.5mg and 3mg demonstrated significantly superior HbA1c and weight reductions vs 1.5mg:

  • HbA1c reduction: 4.5mg (-1.9%; P <.001),  3mg (-1.7%; P =.003), 1.5mg (-1.5%).
  • Weight reduction: 4.5mg (-4.7kg; P <.001), 3mg (-4.0kg; P =.001), 1.5mg (-3.1kg).
  • % of patients with HbA1c <7%: 4.5mg (71%; P <.001), 3mg (65%; P =.006), 1.5mg (57%).

Based on the treatment-regimen estimand, both doses showed significant HbA1c and weight reductions, but only the dulaglutide 4.5mg dose achieved significantly superior reductions vs 1.5mg:

  • HbA1c reduction: 4.5mg (-1.8%; P <.001),  3mg (-1.6%; P=.096), 1.5mg (-1.5%).
  • Weight reduction: 4.5mg (-4.6kg), 3mg (-3.8kg), 1.5mg (-3.0kg).
  • % of patients with HbA1c <7%: 4.5mg (62%), 3mg (56%), 1.5mg (50%).

With regard to safety, the investigational doses of dulaglutide were consistent with the known profile of dulaglutide 1.5mg. The most common adverse reactions were nausea, vomiting and diarrhea.

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Dulaglutide is currently marketed under the brand name Trulicity and is approved as an adjunct to diet and exercise, to improve glycemic control in adults with T2D. It is also indicated to reduce the risk of major cardiovascular (CV) events (eg, CV death, non-fatal MI or non-fatal stroke) in adults with T2DM and established CV disease or multiple CV risk factors.

“AWARD-11 confirmed our expectations that a higher investigational dose of Trulicity would lead to superior blood glucose and weight reductions in people with type 2 diabetes compared to Trulicity 1.5 mg,” said Juan Pablo Frias, MD, Medical Director and Principal Investigator, National Research Institute. “These promising data show higher doses of dulaglutide could be an option for clinicians treating people with type 2 diabetes who may need additional glycemic control due to the progressive nature of the condition.”

Trulicity is available as 0.75mg and 1.5mg single-dose pens for subcutaneous injection.

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