Results from AWARD-11 back up efficacy, safety of higher doses

WASHINGTON — The FDA approved 3.0 mg and 4.5 mg doses of the previously approved glucagon-like peptide 1 (GLP-1) receptor agonist dulaglutide (Trulicity) to further improve glycemic control in adult patients with type 2 diabetes (T2D).

Dulaglutide, which was originally approved in 2014, was previously indicated in conjunction with diet and exercise to treat patients with type 2 diabetes, with subcutaneous, once-weekly doses of either 0.75 mg or 1.5 mg. This new indication is based on data from the phase III AWARD-11 study, which found that “additional doses of [dulaglutide] can lead to further A1C and weight reductions for people with type 2 diabetes whose current treatment may no longer be meeting their needs,” wrote Juan Pablo Frias, MD, Medical Director at the National Research Institute in Los Angeles and principal investigator in the AWARD-11 study, in a company press release from the drug’s manufacturer, Eli Lilly and Company.

AWARD-11 was a phase III, randomized, double-blind, parallel arm study that recruited 1,842 patients with T2D to evaluate the safety and efficacy of the 3.0 and 4.5 mg doses of dulaglutide versus the 1.5 mg dose. For this study, all participants were assigned to receive a 0.75 mg of dulaglutide once a week at baseline, after which the dosage was increased in a step-wise approach at four week intervals to their final randomized maintenance dose — 1.5 mg, 3.0 mg (via a 1.5 mg step), or 4.5 mg (via steps at 1.5 mg and 3.0 mg).

Frias and colleagues used two estimands for the efficacy analyses, they explained in the Journal of the Endocrine Society: an efficacy estimand (data on-treatment without rescue medication) and a treatment-regimen estimand (all data regardless of adherence or initiation of rescue).

“Using the efficacy estimand, the dulaglutide 3 mg and 4.5 mg doses were superior to the dulaglutide 1.5 mg dose for A1C change from baseline (1.5 mg, 1.53%; 3 mg, 1.71% [P=0.003]; 4.5 mg, 1.87% [P<0.001]), % of patients achieving HbA1c <7% (1.5 mg, 57%; 3.0 mg, 65% [P=0.006]; 4.5 mg, 71% [P<0.001]) and body weight change from baseline (1.5 mg, 3.1 kg; 3 mg, 4.0 kg [P=0.001]; 4.5 mg, 4.7 kg [P<0.001]),” Frias and colleagues wrote. “Using the treatment-regimen estimand, dulaglutide 4.5 mg was superior to dulaglutide 1.5 mg for A1C change, while the dulaglutide 3 mg dose did not achieve statistical significance (1.5 mg, 1.54%; 3.0 mg, 1.64% [P=0.096]; 4.5 mg, 1.77% [P<0.001]). Using the treatment-regimen estimand, more patients achieved A1C <7% with higher dulaglutide doses (1.5 mg, 50%; 3 mg, 56%; 4.5 mg, 62%) and results for body weight change were similar to the efficacy estimand (1.5 mg, 3.0 kg; 3 mg, 3.8 kg; 4.5 mg, 4.6 kg), but the approach for type I error control did not permit formal statistical comparisons of these secondary objectives using this estimand.”

Frias and colleagues noted that the most commonly reported adverse events in the AWARD-11 trial were nausea, vomiting, and diarrhea, which was consistent with the drug’s known safety profile—dulaglutide’s label also lists abdominal pain and decreased appetite as potential side effects.

In its press release, Eli Lilly and Company warned that dulaglutide can potentially cause tumors in the thyroid, including thyroid cancer, and advised patients and health care professionals to watch for possible symptoms, including lumps or swelling in the neck, trouble swallowing, hoarseness, or shortness of breath. Patients should not take dulaglutide if they or their family have a history of medullary thyroid carcinoma, multiple endocrine neoplasia syndrome type 2, or a known dulaglutide allergy.

John McKenna, Associate Editor, BreakingMED™

Cat ID: 12

Topic ID: 76,12,730,12,13,192,669,918