by Paolo Fiorina, MD, PhD and Ida Pastore, MD

Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP1-RA) approved for the treatment of type 2 diabetes that requires weekly injection. Currently, regulators have approved two therapeutic doses of dulaglutide, 0.75 mg and 1.5 mg, respectively.

In the last year, results from the REWIND study have shown that the addition of dulaglutide to the medical therapy was able to reduce glucose concentrations, minimize hypoglycemic events, reduce weight and blood pressure but also reduce cardiovascular events in people with type 2 diabetes and additional cardiovascular risk factors.

The results of a new study, the AWARD-11, have been revealed during the last ADA 80^th scientific session. The AWARD-11 was a phase 3, randomized, double-blind, parallel arm study. The aim of the study was to assess the efficacy and safety of dulaglutide 3 mg and 4.5 mg as compared to dulaglutide 1.5 mg in patients with type 2 diabetes poorly controlled with metformin monotherapy.

The study enrolled 1,842 participants with type 2 diabetes, randomized (1:1:1) to once weekly 1.5 mg dulaglutide, 3 mg dulaglutide and 4.5 mg dulaglutide and a follow up of 52 weeks, after a first evaluation of primary endpoint at 36 weeks.

Results show that:

• Dulaglutide 3 mg and 4.5 mg met the primary efficacy endpoint of superiority compared to dulaglutide 1.5 mg, as revealed by A1c reduction from baseline.
• Dulaglutide 3 mg and 4.5 mg compared to dulaglutide 1.5 mg improved fasting serum glucose and body weight.
• Moreover, percentage of patients reaching levels of A1c below of 7% is better with Dulaglutide 3 mg and 4.5 mg respect to dulaglutide 1.5 mg
• All parameters evaluated improved as dose increases

When compared to dulaglutide 1.5 mg, dulaglutide 3 mg and dulaglutide 4.5 mg were able to meet the multiple endpoints after 36 weeks and to maintain them greater after 52 weeks, highlighting durability of dulaglutide over time.

In conclusion, this study confirmed the efficacy and safety of dulaglutide at 3 mg and 4.5 mg. Moreover, incremental doses of dulaglutide have shown to exert greater effects on weight loss and on glucose control, either in term of A1c than fasting serum glucose.