Francesco Giorgino, Maria Yu, Nan Zhang, Imre Pavo, Samuel Dagogo-Jack, Baptist Gallwitz, Vivian Thieu, Kenneth E. Robertson, Luis-Emilio Garcia-Perez
To evaluate the efficacy and safety of dulaglutide 1.5 mg and 0.75 mg in type 2 diabetes patients by subgroups of gender, duration of diabetes, and baseline HbA1c in the dulaglutide clinical development program (AWARD-1 to -6 and -8 clinical trials).
Materials and methods
Change in HbA1c was analysed by gender, duration of diabetes (<5 years, ≥5 years and <10 years, ≥10 years), and baseline HbA1c (<8.5%, ≥8.5%) in pooled and individual studies. Changes from baseline in weight, hypoglycaemia, and gastrointestinal adverse events were evaluated for individual trials.
In the pooled analysis of patients treated with dulaglutide 1.5 mg at 6 months, the reductions of HbA1c from baseline were similar across gender (least squares mean [95% CI]. male: -1.26% [-1.36%, -1.16%]; female: -1.33% [-1.43%, -1.24%]) and among duration of diabetes subgroups (<5 years: -1.32% [-1.43%, -1.22%]; ≥5 years and <10 years: -1.33% [-1.43%, -1.22%]; ≥10 years: -1.24% [-1.35%, -1.14%]). Patients with baseline HbA1c ≥8.5% had greater HbA1c reductions than patients with baseline HbA1c <8.5%, (≥8.5%: -1.86% [-1.97%, -1.75%]; <8.5%: -1.02% [-1.12%, -0.93%]). Reductions in fasting blood glucose (FBG) were consistent with HbA1c changes. Similar results were observed with dulaglutide 0.75 mg. In general, body weight changes were similar among duration of diabetes and between baseline HbA1c subgroups respectively; female patients had a numerically greater weight loss or less weight gain than male patients with both dulaglutide doses. There was no clinically meaningful difference in trend of hypoglycaemia by gender or duration of diabetes. Hypoglycaemia incidence and rate were generally lower in patients with baseline ≥8.5% than with <8.5%, except for the AWARD-4 study (combination with mealtime insulin).
Across the AWARD studies, dulaglutide demonstrated significant improvement of glycaemic control irrespective of gender, duration of diabetes, or baseline HbA1c, with greater HbA1c and FBG reductions in patients with higher baseline HbA1c. Dulaglutide was well-tolerated with a safety profile similar to other GLP-1 receptor agonists.