Dulaglutide Bests Sitagliptin: Review of AWARD-5

March 16, 2015

At 52 weeks, dulaglutide resulted in significantly greater reductions in HbA1c, FPG, and weight compared with the DPP-4 inhibitor sitagliptin.

Once-weekly injections of the glucagon-like peptide 1 (GLP-1) receptor agonist dulaglutide provided patients with type 2 diabetes (T2DM) superior glucose control compared with treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin, according to the results of the phase III AWARD-5 trial published recently in Diabetes Care.

At 52 weeks, treatment with dulaglutide at both doses studied resulted in significantly better reductions in HbA1c (A1c), fasting plasma glucose, and weight compared with sitagliptin with no reports of severe hypoglycemia. 

“The AWARD-5 trial confirmed that dulaglutide is an effective treatment option in metformin-treated patients who require further treatment intensification,” wrote Michael Nauck, MD, of Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany, and colleagues. “These results suggest a favorable benefit/risk profile for dulaglutide as an add-on intervention in metformin-treated type 2 diabetic patients.”

The AWARD-5 trial included 1,098 patients with uncontrolled, metformin-treated T2DM who were randomly assigned to once-weekly dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo. The median age of patients was 54 years and the median baseline A1c was 8.8%.

At week 52 of treatment, patients assigned dulaglutide had significantly greater reductions in A1c at both doses compared with patients assigned sitagliptin (1.5 mg, -1.10% and 0.75 mg, -0.87% vs sitagliptin, -0.39%; P<.001 for both comparisons). In addition, significantly more patients assigned to dulaglutide were able to achieve the target A1c of <7.0% compared with patients assigned sitagliptin (1.5 mg, 58% and 0.75 mg, 49% vs. 33%; P<.001 for both). The same was true for the percentage of patients able to achieve a goal A1c of ≤6.5%.

Dulaglutide treatment resulted in an improvement in fasting plasma glucose within 2 weeks of treatment initiation. Dulaglutide-treated patients also had significantly greater reductions in fasting plasma glucose by week 52 compared with patients treated with sitagliptin (P<.001).

              ►►Early reduction in FPG is a good measure of glycemic                response and allows patients and clinicians to gauge
             therapeutic effect soon after initiation of treatment.

“This early effect is important from a clinical perspective, in that it is a readily available measure of glycemic response, allowing patients and health care providers to gauge an indication of therapeutic effect soon after the initiation of therapy,” the researchers wrote.

The researchers also examined mean weight change and found that treatment with dulaglutide resulted in a change of -3.03 kg for dulaglutide 1.5 mg and -2.60 kg for dulaglutide 0.75 mg compared with -1.53 kg for sitagliptin (P<.001 for both).

Patients assigned dulaglutide did have a higher incidence of gastrointestinal adverse events, most commonly nausea, vomiting, and diarrhea. However, the incidence of hypoglycemic events was very low for both dulaglutide doses.

Dulaglutide was approved by the FDA in September 2014 as a once-weekly injection for patients with T2DM.

References:

Nauck M, Weinstock RS, Umpierrez GE, et al. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled diabetes trial (AWARD-5). Diabetes Care. 2014;37:2149-2158.