42
The
nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)
BP-1
EFFICACY OF INVESTIGATIONAL DULAGLUTIDE DOSES OVERALL AND BY BASELINE HBA1C AND BMI: EXPLORATORY SUBGROUP ANALYSIS OF THE AWARD-11 TRIAL 1
ENZO BONORA, 2JUAN FRIAS, 3LUIS NEVAREZ RUIZ, 4ZHUOXIN YU, 4 ZVONKO MILICEVIC, 4RALEIGH MALIK, 4ANGELYN BETHEL, 4DAVID COX, 5 THOMAS LEW (NON-AUTHOR PRESENTER) 1
University of Verona, Verona, Italy; 2National Research Institute, California, USA; 3Hospital Angeles Chihuahua, Chihuahua, Mexico; 4Eli Lilly and Company, Indianapolis, Indiana, USA; 5Eli Lilly and Company, Taipei, Taiwan, R.O.C
Background and aims: Dulaglutide (DU) is approved at doses of 0.75 and 1.5 mg for type 2 diabetes (T2D). The AWARD-11 trial assessed whether higher DU doses (3 mg and 4.5 mg) provide further improvements over the 1.5 mg dose in glucose and body weight (BW) in patients with T2D inadequately controlled with metformin monotherapy. Exploratory prespecified subgroup analyses assessed the effect of DU on HbA1c and BW reduction by baseline HbA1c (< 8.5% or ≥ 8.5%) and BMI (< or ≥ median [34.2 kg/m2]). Materials and methods: Patients were randomized (1:1:1) to once-weekly DU 1.5 mg (n = 612), DU 3 mg (n = 616), and DU 4.5 mg (n = 614). All patients initiated once-weekly DU 0.75 mg for 4 weeks, followed by step-wise dose escalation every 4 wks to the randomized dose. The primary objective was change in HbA1c from baseline at 36 wks. Secondary objectives included change in BW and % of pts achieving HbA1c < 7% at 36 wks. Results: At baseline patients had a mean age of 57.1 yrs, HbA1c of 8.6%, and BW of 95.7 kg. At the 36-wk primary endpoint, both the DU 3 mg and 4.5 mg doses were superior to the DU 1.5 mg dose for HbA1c change (1.5 mg, -1.5%; 3 mg, -1.7% [p = 0.003]; 4.5 mg, -1.9% [p < 0.001]), % of patients achieving HbA1c < 7% (1.5 mg, 57%; 3.0 mg, 65% [p = 0.006]; 4.5 mg, 71% [p < 0.001]) and BW (1.5 mg, -3.1 kg; 3 mg, -4.0 kg [p = 0.001]; 4.5 mg, -4.7 kg [p < 0.001]). Treatment group differences in HbA1c change favored the higher doses vs the 1.5-mg dose in each HbA1c subgroup, with dose-related HbA1c improvements being larger in the higher baseline HbA1c subgroup. BW reduction was dose related in each baseline HbA1c subgroup but was larger among patients with lower baseline HbA1c. Treatment effects on HbA1c were similar between baseline BMI subgroups. Absolute BW reduction was larger across dose groups in the higher baseline BMI subgroup, but treatment group differences were similar between subgroups. Common adverse events were similar between HbA1c and BMI subgroups. Conclusions: In patients with T2D and inadequate glycemic control on metformin, escalation from DU 1.5 mg to DU 3 mg or DU 4.5 mg once-weekly provided clinically relevant, dose-related 210
