Individuals with type 2 diabetes who were taking prandial lispro (Humalog—Eli Lilly) in combination with once-weekly dulaglutide (Trulicity—Eli Lilly) achieved better glycemic control than those on prandial lispro plus bedtime glargine (Lantus—Sanofi–Aventis), according to results of a recent trial.
The AWARD–4 study was an open-label, noninferiority trial that compared once-weekly dulaglutide with insulin glargine, both given in combination with prandial lispro (with or without metformin), in 884 patients with uncontrolled type 2 diabetes. Investigators randomized patients to receive dulaglutide 1.5 mg (n = 295), dulaglutide 0.75 mg (n = 293), or insulin glargine (n = 296) for 52 weeks. Approximately three-fourths of patients also received metformin therapy. The primary endpoint was the change in glycosylated hemoglobin A1C (HbA1C) from baseline to week 26. At week 26, there were greater reductions in HbA1C in both dulaglutide groups compared with the glargine group. The adjusted mean difference versus glargine was −0.22% in the dulaglutide 1.5-mg group (P = 0.005) and −0.17% in the dulaglutide 0.75-mg group (P = 0.015). Similar results were observed after 52 weeks of therapy. In addition, a greater proportion of patients in both dulaglutide groups achieved HbA1C targets of less than 7.0% at 26 weeks compared with glargine patients, and a greater proportion in the dulaglutide 1.5-mg group achieved HbA1C targets of less than 7.0% at 52 weeks and less than 6.5% at 26 weeks compared with the glargine group. Dulaglutide was also associated with weight loss or neutrality as compared with a weight increase in individuals receiving glargine. At week 26, adjusted mean changes in body weight were −0.87 kg in the 1.5-mg group, +0.18 kg in the 0.75-mg group, and +2.33 kg in the glargine group, with similar changes at week 52.
Trial results support the use of a long-acting GLP-1 agonist in combination with prandial insulin in patients with type 2 diabetes not controlled by one or two daily basal insulin doses. In an accompanying commentary, Ostoft and Christensen wrote, “Blonde and colleagues’ trial could raise the question of whether mealtime insulin should be initiated instead of basal insulin in a patient receiving a GLP-1 receptor agonist.” They concluded that the current trial results “are of great clinical and academic interest by providing a novel perspective on treatment intensification in patients with type 2 diabetes.”
Educate patients that results of a new study suggest a long-acting GLP-1 agonist combined with mealtime insulin may be an option for some individuals with type 2 diabetes instead of intensifying a basal–bolus insulin regimen.
Blonde L et al. Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD–4): a randomised, open-label, phase 3, non-inferiority study.Lancet. 2015;385:2057–66.
Ostoft SH et al. An alternative combination therapy for type 2 diabetes [Editorial]. Lancet. 2015;385;2020–2.
Focus on Diabetes Care
Charles D. Ponte, Section Advisor