Comparing Efficacy and Safety of Different Doses of Dulaglutide in Metformin-Treated Patients with Type 2 Diabetes

Comparing Efficacy and Safety of Different Doses of Dulaglutide in Metformin-Treated Patients with Type 2 Diabetes
Larissa Yehle, PharmD, Coborns CSC

Background: Type 2 diabetes is a chronic disease that often requires more than one medication to reach control. Current American Diabetes Association guidelines recommend the addition of a glucagon-like peptide-1 receptor agonist (GLP-1RA) to metformin therapy because of their efficacious glucose-lowering properties, low hypoglycemia risk, weight loss benefit, and proven cardiovascular benefit. 

Objective: The purpose of this study was to evaluate the safety and efficacy of dulaglutide at doses of 3 mg and 4.5 mg versus 1.5 mg in patients with type 2 diabetes who were uncontrolled with metformin monotherapy. The study looked at whether or not doses above 1.5 mg of dulaglutide showed superiority in reducing A1C levels after 36 weeks. 

Study Design: This study was a double-blind, randomized, parallel armed trial conducted in 203 sites across 15 countries. To be eligible for this study, the participant must have been over the age of 18, had type 2 diabetes for more than six months, an A1C between 7.5-11% at screening, naive to both GLP-1RA and insulin, and a metformin dose of 1500 mg or greater for at least three months. A minimum body max index threshold was also used in an attempt to avoid limitations of gastrointestinal tolerability during dose titrations. Individuals were excluded if they were taking antidiabetic medications besides metformin within three months of randomization, had calcitonin levels at or above 20 ng/L, had pancreatitis/ketoacidosis/hyperosmolar state or a recent cardiovascular event, or had active cancer. The primary outcome assessed was the change in A1C from baseline over 36 weeks. The secondary outcomes assessed were the proportion of patients achieving an A1C less than 7%, change in fasting baseline serum glucose levels, and change from baseline in body weight. The 1842 patients enrolled in the study were split into three treatment groups as follows: dulaglutide 1.5mg, dulaglutide 3mg, and dulaglutide 4.5mg.

Results:  Compared with the 1.5 mg dose, the 3 mg and the 4.5 mg doses of dulaglutide resulted in significantly greater A1C reductions after 36 weeks (P < 0.001). Significantly more patients achieved an A1C of less than 7% in the treatment groups with the 3 mg and 4.5 mg dulaglutide. In addition, those who were taking the 4.5 mg dose of dulaglutide were two times more likely to reach their A1C target compared to those on the 1.5 mg dose (P < 0.001). Only the 4.5 mg dose was superior in terms of lowering the fasting blood sugar levels. Dulaglutide 4.5 mg was superior to 1.5 mg in lowering body weight (P < 0.001). The proportion of patients reporting at least one treatment-emergent adverse event was similar across all groups. The most common adverse effect reported was stomach upset, which tended to appear early in the trial and abate thereafter. Gastrointestinal upset increased as the dose increased overall. 

Conclusions/Key Point: Patients with type 2 diabetes previously taking metformin with inadequate glycemic control could benefit from initiating and titrating dulaglutide from 1.5 mg to 3 mg or 4.5 mg over time to improve glycemic control and reduce body weight. Stomach upset might occur with dose increases, but would likely abate with time and be mild in severity.



  1. Frais J, Bonora E, Ruis L, et al. Efficacy and safety of dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5mg in metformin - treated patients with type 2 diabetes in a randomized controlled trial (AWARD-11). Diabetes Care. 2021;44(3):765-773. doi: 10.2337/dc20-1473