• Diabetes & Endocrinology Clinical Trials
• Hyperglycemia/Hypoglycemia
• Diabetes Mellitus

• Endocrinology
• Diabetes & Metabolic Syndrome
• Diabetes & Endocrinology Clinical Trials
• Hyperglycemia/Hypoglycemia
• Diabetes Mellitus

Results from the Assessment of Weekly Administration of LY2189265 in Diabetes-6 [AWARD-6; NCT01624259] trial, presented by Santiago Tofé Provedano, MD, Clinica Juaneda, Endocrinologia, Palma de Mallorca, Spain, show that once-weekly dulaglutide provides glycemic control that is noninferior to once-daily liraglutide with a similar safety and tolerability profile [Dungan KM et al. Lancet. 2014].

AWARD-6 was a phase 3 randomized, open-label, parallel-arm, 26-week study comparing the efficacy and safety of once-weekly dulaglutide 1.5 mg (n = 299), a long-acting glucagon-like peptide–1 receptor agonist, with once-daily liraglutide 1.8 mg (n = 300). Liraglutide was initiated at a dose of 0.6 mg/d and was titrated to 1.2 mg/d in week 2 and 1.8 mg/d in week 3. The study comprised type 2 diabetes (T2D) patients with an HbA_1c ≥ 7% and ≤ 10% who were on a stable dose of metformin (≥ 1500 mg) for ≥ 3 months.

Participants (∼ 50% women and mostly white [86%]) had a mean age of 57 years and a mean HbA_1c of 8.1%. Most were obese (mean body mass index [BMI] 34 kg/m²). The mean duration of diabetes was 7 years; mean daily metformin dose was more than 2000 mg. The primary study endpoint was the noninferiority of the change in HbA_1c from baseline to 26 weeks using a noninferiority margin of 0.4%. Superiority at week 26 (controlled for Type 1 error) was a key secondary endpoint and was to be tested if the noninferiority endpoint was met.

Dulaglutide was noninferior to liraglutide at 26 weeks (mean difference in HbA_1c −0.06%; 95% CI, −0.19 to 0.07; P _{noninferiority} < .001; Figure 1). The reductions in HbA_1c were similar throughout time and did not differ based on HbA_1c at baseline (ie, < 7.0% vs ≤ 6.5%). The effect on postprandial and fasting blood glucose was similar with both drugs. The mean difference in HbA_1c was not superior with dulaglutide as compared with liraglutide.

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Figure 1.

HbA_1c Change From Baseline at Week 26

LSM, least squares mean. ^aTreatment difference (nominal 95%) CI, mixed-model repeated-measures analysis.Reprinted from The Lancet, 384, Dungan KM, Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial, 1349–1357, Copyright 2014, with permission from Elsevier.

Both groups experienced significant weight reduction; however, patients treated with liraglutide had greater reductions in weight compared with dulaglutide-treated patients (0.7 kg, P < .05, Figure 2).

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Figure 2.

Body Weight Change Throughout Time

LSM, least squares mean.* P < .05.Reprinted from The Lancet, 384, Dungan KM, Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial, 1349–1357, Copyright 2014, with permission from Elsevier.

Similar numbers of patients reported adverse events (AEs). As expected, the most common AEs were gastrointestinal. These included nausea (20% and 18% for dulaglutide and liraglutide, respectively), diarrhea (both 12.0%), dyspepsia (8% and 6%), and vomiting (7% and 8%). The rate of study or study drug discontinuation due to any AE was similar (18 [6%] in each group). The rate of hypoglycemia (≤ 3.9 mmol/L ± symptoms) events was low: 0.3/patient/y with dulaglutide and 0.5 with liraglutide. No episodes of severe hypoglycemia were reported. There were no incidences of adjudicated pancreatitis or pancreatic cancer.

The once-weekly dosing regimen of dulaglutide allowed patients to administer substantially fewer injections while achieving similar glycemic benefits. In this study, the compliance rate (defined as patients achieving > 75% of prescribed doses) for dulaglutide was 98.5% compared with 97.8% for liraglutide [Dungan KM et al. Lancet. 2014]. An additional study is needed to determine whether long-term use of once-weekly drugs like dulaglutide might improve treatment compliance compared with more frequently administered regimens.

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