Efficacy and Safety of Dulaglutide Versus Sitagliptin After 52 Weeks in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-5)

Abstract

OBJECTIVETo compare the efficacy and safety of two doses of once-weekly dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in uncontrolled, metformin-treated patients with type 2 diabetes. The primary objective was to compare (for noninferiority and then superiority) dulaglutide 1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A1c (HbA1c) at 52 weeks.RESEARCH DESIGN AND METHODSThis multicenter, adaptive, double-blind, parallel-arm study randomized patients (N = 1,098; mean baseline age 54 years; HbA1c 8.1% [65 mmol/mol]; weight 86.4 kg; diabetes duration 7 years) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo (placebo-controlled period up to 26 weeks). The treatment period lasted 104 weeks, with 52-week primary end point data presented.RESULTSThe mean HbA1c changes to 52 weeks were (least squares mean ± SE): −1.10 ± 0.06% (−12.0 ± 0.7 mmol/mol), −0.87 ± 0.06% (9.5 ± 0.7 mmol/mol), and −0.39 ± 0.06% (4.3 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin, respectively. Both dulaglutide doses were superior to sitagliptin (P < 0.001, both comparisons). No events of severe hypoglycemia were reported. Mean weight changes to 52 weeks were greater with dulaglutide 1.5 mg (−3.03 ± 0.22 kg) and dulaglutide 0.75 mg (−2.60 ± 0.23 kg) compared with sitagliptin (−1.53 ± 0.22 kg) (P < 0.001, both comparisons). The most common gastrointestinal treatment-emergent adverse events in dulaglutide 1.5- and 0.75-mg arms were nausea, diarrhea, and vomiting.CONCLUSIONSBoth dulaglutide doses demonstrated superior glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability and safety profile.

Once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide is non‐inferior to once‐daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26‐week randomized phase III study

“…The HbA1c reduction observed at 26 weeks in the present study in Japanese patients with type 2 diabetes is consistent with the upper range of reductions seen in the global AWARD studies for dulaglutide (0.75 or 1.5 mg) 11, 12, 13, 14. It has been previously reported that GLP‐1 receptor agonists exert greater HbA1c‐lowering effects in Asian compared with non‐Asian people, and it has been suggested that differences in BMI between the ethnicities may be a contributing factor in the observed differential effects 19.…”

“…The safety profile of dulaglutide in this study (Table 2) was similar to that seen in previous GLP‐1 receptor agonist studies 11, 12, 13, 14, 17, 18. The most‐frequently reported adverse event was nasopharyngitis, reported by 12–13% of patients in the active treatment groups.…”

Dulaglutide in the treatment of adult type 2 diabetes: a perspective for primary care providers

“…In AWARD-3 study (monotherapy vs. metformin), treatment with dulaglutide also resulted in significant reductions in postprandial glucose (PPG) from baseline after 2 weeks and this reduction lasted through the study [28]. Consistent with the early reduction in FBG and PPG, dulaglutide was shown to reduce HbA1c in patients with T2D as early as 4 weeks [28,30,31,33] after the start of treatment, and the reduction was shown to be sustained through 104 weeks [31].…”

“…The range of HbA1c reduction from baseline to the primary end point with dulaglutide 1.5 mg was −0.78% to −1.64% and −0.71% to −1.59% for dulaglutide 0.75 mg, and −0.39% to −1.41% for active comparators ( Figure 3 and Table 1) in the seven studies included in this report [26][27][28][29][30][31][32][33]. Across studies, dulaglutide 1.5 mg was superior, based on HbA1c change from baseline, to placebo in AWARD-1, AWARD-5, and AWARD-8 (Table 1; placebo data will not be discussed further in the context of this manuscript), and superior to the active comparators evaluated: metformin, sitagliptin, exenatide BID, and insulin glargine (the comparator in two separate studies), and noninferior to liraglutide at the primary end point.…”

“…These Phase 3 studies were designed to assess efficacy, safety, and PROs in patients across different stages of the T2D treatment continuum from monotherapy (AWARD-3), in patients taking concomitant sulfonylurea (SU) (AWARD-8), metformin (AWARD-5 and AWARD-6), metformin and thiazolidinedione (TZD) (AWARD-1), metformin and SU (AWARD-2), or in combination with prandial insulin with or without metformin (AWARD-4) with a study duration of 24-104 weeks ( Figure 2) [26][27][28][29][30][31][32][33]. A diverse patient population representing the continuum of T2D progression was examined across the seven trials, with a mean baseline age of 54.1-59.4 years, a mean duration of diabetes of 2.6-12.7 years, mean HbA1c of 7.6-8.5%, mean weight of 85.5-96.0 kg, FBG of 154-177 mg/dL, and previous treatment ranging from antihyperglycemic medication naive to third-line therapy.…”