Among patients with type 2 diabetes who had poor glycemic control with metformin therapy, weekly dulaglutide resulted in clinically relevant weight loss and glycated hemoglobin (HbA1c) reduction. These findings, from a randomized, double-blind, parallel-arm study, were published in Diabetes Care.
Patients (N=1842) with type 2 diabetes mellitus were recruited from 203 sites in 15 countries for the Assessment of Weekly Administration of LY2189265 in Diabetes-11 (AWARD-11) trial. Patients were randomly assigned in a 1:1:1 ratio to receive 1.5 (n=612), 3.0 (n=616), or 4.5 (n=614) mg weekly dulaglutide subcutaneous injection for a 2-week lead-in period and then treatment for 52 weeks followed by a 4-week safety assessment. Randomization occurred after stratifying patients by low (<8.5%) or high (³8.5%) HbA1c. All patients were initiated on once-weekly 0.75 mg dulaglutide for 4 weeks, and then the dose was escalated to the randomized dose. Efficacy and safety were assessed.
Patients had a mean age of 57.1 (±10.0) years, and 48.8% were women. Patients had been diagnosed an average of 7.6 (±5.7) years ago, their baseline HbA1c was 8.6% (±1.0%), and their body mass index was 34.2 (±6.3) kg/m2.
At 36 weeks, the least-square mean change of HbA1c was -1.54%, -1.64%, and -1.77% for the low-, intermediate-, and high-dose groups, respectively. Patients in the 4.5-mg group showed the greatest improvement of HbA1c, which was significant compared with the 1.5-mg group (estimated treatment difference [ETD], -0.24%; 95% CI, -0.36% to -0.11%; P <.001).
Compared with the low-dose group, patients receiving 4.5 mg were more likely to have less than 7% (odds ratio [OR], 2.2; 95% CI, 1.7-3.0; P <.001) or 6.5% or less (OR, 2.0; 95% CI, 1.5-2.6; P <.001) change of HbA1c at 36 weeks.
Body weight was significantly decreased among the 3.0-mg (ETD, -0.9; 95% CI, -1.4 to -0.4 kg; P =.001) and 4.5-mg (ETD, -1.6; 95% CI, -2.1 to -1.1 kg; P <.001) groups compared with the 1.5-mg cohort at 36 weeks.
Among the low-, intermediate-, and high-dose recipients, the most common adverse events were nausea (14.2% vs 16.1% vs 17.3%), diarrhea (7.7% vs 12.0% vs 11.6%), and vomiting (6.4% vs 9.1% vs 10.1%), which caused the majority of drug discontinuations. Serious events (8.3% vs 6.8% vs 6.2%) and death (0.5% vs 0.6% vs 0.7%) were rare.
The results of this study may not be generalizable among a population of patients with type 2 diabetes who are not overweight or have superior glycemic control on metformin.
The study authors concluded 3.0 or 4.5 mg weekly subcutaneous injections of dulaglutide favorably lowered HbA1c concentrations and weight among patients with type 2 diabetes and poor glycemic control without increased instances of serious adverse events compared with the well-established dose of 1.5 mg dulaglutide.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Frias J P, Bonora E, Ruiz L N, et al. Efficacy and safety of dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5 mg in metformin-treated patients with type 2 diabetes in a randomized controlled trial (AWARD-11). Published online January 4, 2021. Diabetes Care. doi:10.2337/dc20-1473