Higher Doses of Dulaglutide Safe, Efficacious in Patients with Type 2 Diabetes

Juan Pablo Frias, MD

A post-hoc analysis of the AWARD-11 trial showed that higher doses of dulaglutide were highly efficacious and safe in reducing A1C levels in patients with type 2 diabetes regardless of baseline levels.

The study was led by Juan Pablo Frias, MD, National Research Institute, CA, and presented at the Endocrine Society’s Annual Meeting (ENDO 2021).

“This exploratory post hoc analysis of AWARD-11 assessed the effect of dulaglutide on A1C reduction by clinically-relevant baseline A1C subgroups (<8%; 8%-<9%; 9%-<10%; ≥10%) and the proportion of patients achieving A1C <7% in these subgroups through 36 and 52 weeks,” the investigators wrote.

Patients (n = 1842) were randomized 1:1:1 to 1.5 mg of dulaglutide, 3 mg. or 4.5 mg— all of which were administered once weekly. However, all patients were administered duraglutide 0.75 mg in their first 4 weeks of treatment before stepwise administration to their assigned dose.

Frias and colleagues used a mixed effects model for repeated measures within the A1C subgroups in order to assess the change in A1C from baseline to 36 and 52 weeks.

The team also used a longitudinal logistic regression model within subgroups to analyze those patients who achieved A1C <7% at weeks 36 and 52.

As such, the team reported that duraglutide 1.5 mg reduced A1C levels across all baseline categories at week 36 (range, -1.0% to -2.2%). This effect was maintained through week 52 (range, -1.0% to -2.1%).

However, greater A1C reductions were noted among patients in each baseline category randomized to 3 mg or 4.5 mg. Reductions were more significant for those with higher baseline A1C.

“More patients randomized to 3 mg or 4.5 mg achieved A1C <7% versus those on 1.5 mg at 36 weeks regardless of baseline A1C, but the difference across dose groups was greater at higher baseline A1Cs,” the investigators emphasized.

Specifically, they noted that more than half of the patients in each A1C category who were randomized to dulaglutide 4.5 achieved levels <7% (A1C < 8%, 83%; 8-<9%, 73%; 9-<10%, 64%; ≥10, 55%; P = .096)

These dose-related effects and proportions were notably consistent through week 52, the team indicated.

In terms of safety profile, gastrointestinal adverse events were similar across A1C categories.

“Glycemic control as measured by A1C and proportion of patients achieving A1C <7% was improved with duraglutide dose escalation from 1.5 mg to 3 mg or 4.5 mg across a spectrum of clinically relevant baseline A1C categories without increasing incidence of GI adverse events,” the team noted.

Those with baseline A1C levels of 9-<10% and ≥10% achieved greater dose-related improvements in glycemic controls—as compared with lower baselines.

A majority of those randomized to the highest duraglutide dose (4.5 mg)—regardless of baseline category—reached their glycemic target.

The study, “Efficacy of Dulaglutide Expanded Doses by Baseline A1C Categories: Post Hoc Analysis of AWARD-11,” was presented at ENDO 2021