Effect of once-weekly Dulaglutide by baseline β-cell function in the AWARD program

Research Question:

Dulaglutide (DU), a once-weekly GLP-1 receptor agonist, was studied in the AWARD trial program in adult patients with T2D and demonstrated significant HbA1c reduction and weight loss potential. A pooled post-hoc subgroup analysis was conducted on studies AWARD-1, 3, 5 and 6 to evaluate the effects of DU by baseline β-cell function (as estimated by HOMA2-%B).

Methodology:

Patients were categorized into three subgroups defined by tertiles (low, medium, high) of baseline HOMA2-%B. Fasting C-peptide was available for AWARD-1, 3, and 6 (low, n = 440; medium, n = 459; high, n = 447), and fasting insulin for AWARD-1, 3, and 5 (low, n = 495; medium, n = 510; high, n = 496), to calculate HOMA2-%B.

Findings:

Across DU arms of these trials, patients had a mean baseline age of 54 – 57 years, duration of diabetes of 3 – 9 years, HbA1c of 7.6 – 8.2%, and BMI of 31 – 34 kg/m². In subgroups of patients with low HOMA2-%B, the baseline fasting C-peptide and insulin were lower while baseline fasting glucose, HbA1c, and duration of diabetes were higher than the subgroups of patients with high HOMA2-%B. Reductions of HbA1c from baseline to Week 26 in response to DU treatment tended to be higher in the high HOMA2-%B vs. the low HOMA2-%B (C-peptide HOMA2-%B DU 1.5 mg: -1.18% vs. -1.00% and DU 0.75 mg: -0.91% vs. -0.72%). But the differences between these reductions in the low and high HOMA-2-%B tertiles were small and may have limited clinical relevance.

Conclusion:

In conclusion, patients treated with DU demonstrated clinically relevant HbA1c reductions regardless of estimated baseline β-cell function.