Higher dulaglutide doses improve response in T2D patients uncontrolled on metformin

Treatment with dulaglutide in type 2 diabetes (T2D) patients with inadequate response to metformin yields meaningful dose-related reductions in blood glucose and body weight without compromising safety, as shown in a study.

The study included 1,842 patients with T2D inadequately controlled on metformin. They were randomized to receive dulaglutide at 1.5 mg, 3.0 mg, or 4.5 mg once weekly for 52 weeks. Two estimands were applied in the efficacy analyses, namely treatment regimen (regardless of treatment discontinuation or rescue medication) and efficacy (on treatment without rescue medication).

The mean HbA_1c and body mass index (BMI) at baseline were 8.6 percent (70 mmol/mol) and 34.2 kg/m², respectively.

At 36 weeks, the highest dose proved superior to the lowest dulaglutide dose in terms of the primary endpoint of blood glucose control. The corresponding HbA_1c reductions associated with the 4.5-mg vs 1.5-mg dose were −1.77 percent vs −1.54 percent (estimated treatment difference [ETD], −0.24 percent [−2.6 mmol/mol]; p<0.001) under the treatment-regimen estimand, and −1.87 percent vs −1.53 percent (ETD, −0.34 percent [−3.7 mmol/mol]; p<0.001) under the efficacy estimand.

Dulaglutide 3.0 mg also produced significantly greater HbA_1c reductions compared with the lowest dose under the efficacy estimand (ETD, −0.17 percent [−1.9 mmol/mol]; p=0.003) but not the treatment-regimen estimand (ETD, −0.10 percent [−1.1 mmol/mol]; p=0.096).

In terms of weight loss, 36-week results favoured the 4.5-mg than the 1.5-mg dose for both estimands (treatment regimen: −4.6 vs −3.0 kg; ETD, −1.6 kg; p<0.001; efficacy: −4.7 vs −3.1 kg; ETD, −1.6 kg; p<0.001).

Safety profile was similar across the three dulaglutide doses. Common adverse events were nausea (13.4 percent, 15.6 percent, and 16.4 percent, respectively) and vomiting (5.6 percent, 8.3 percent, and 9.3 percent, respectively).