A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes (AWARD-8)

Abstract

Aims: To evaluate the safety and efficacy of once-weekly dulaglutide 1.5 mg, a long-acting glucagon-like peptide-1 receptor agonist, compared with placebo in patients with type 2 diabetes (T2D) on glimepiride monotherapy.

Methods: This phase III, randomized (4 : 1; dulaglutide:placebo), double-blind, placebo-controlled, 24-week study compared the safety and efficacy of once-weekly dulaglutide 1.5 mg with placebo in sulphonylurea-treated (≥half-maximal dose, stable ≥3 months) patients (N = 300) with T2D and inadequate glycaemic control [glycated haemoglobin (HbA1c) ≥7.5 and ≤9.5% (≥58 mmol/mol and ≤80 mmol/mol)]. Analysis was carried out according to intention-to-treat.

Results: At baseline, the mean participant age was 58 years; mean HbA1c was 8.4% (68 mmol/mol) and mean weight was 85.5 kg. Dulaglutide 1.5 mg was superior to placebo at 24 weeks for HbA1c reduction from baseline with a between-group HbA1c difference of -1.3% [95% confidence interval (CI) -1.6, -1.0] or -14 mmol/mol (95% CI -17, -11); p < 0.001. A greater proportion of participants in the dulaglutide group reached an HbA1c level of <7.0% (53 mmol/mol) compared with placebo (55.3% vs 18.9%; p < 0.001). Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo (between-group difference -1.86 mmol/l (95% CI -2.58, -1.14) or -33.54 mg/dl (95% CI -46.55, -20.53); p < 0.001. Weight was decreased significantly from baseline in the dulaglutide group (p < 0.001); the between-group difference was not significant. The most common treatment-emergent adverse events for dulaglutide 1.5 mg were gastrointestinal: nausea (10.5%), diarrhoea (8.4%) and eructation (5.9%). Total hypoglycaemia was higher with dulaglutide 1.5 mg vs placebo (2.37 and 0.07 events/participant/year, respectively; p = 0.025). No severe hypoglycaemia was reported.

Conclusions: Once-weekly dulaglutide 1.5 mg had a favourable benefit/risk profile when added to glimepiride monotherapy.

Keywords: dulaglutide; glucagon-like peptide-1; type 2 diabetes.

Figure 1

Participant disposition. ^aRequired glycaemic rescue: dulaglutide 1.5 mg, n = 5 (2.1%); placebo, n = 7 (11.7%). ^bOne patient was randomized to dulaglutide but not treated (investigator decision, entry criteria not met).

Figure 2

Trial outcome measures: (A) Change in glycated haemoglobin (HbA1c) from baseline at week 24, intention‐to‐treat (ITT) without post‐rescue values [mixed model for repeated measures (MMRM)], *p < 0.001, change from baseline; #p < 0.001, dulaglutide versus placebo. (B) HbA1c values change from baseline over time to week 24 (MMRM), *p < 0.001, change from baseline; #p < 0.001, dulaglutide versus placebo. (C) Percentage of patients achieving HbA1c targets, ITT, without post‐rescue values, Logistic regression, #p < 0.001, dulaglutide versus placebo. (D) Change in fasting serum glucose concentrations from baseline to week 24 (central laboratory) ITT without post‐rescue values analysis of covariance (LOCF) *p < 0.001, change from baseline; #p < 0.001, dulaglutide vs placebo. (E) Seven‐point self‐monitored plasma glucose (SMPG) by time of day, ITT without post‐rescue values (MMRM), *p < 0.001, †p < 0.050, change from baseline; # p < 0.001, dulaglutide vs placebo. Solid lines indicate baseline, dashed lines indicate endpoint data. (F) Body weight change over time from baseline to 24 weeks, ITT without post‐rescue values (MMRM), dulaglutide change from baseline **p < 0.050, *p < 0.001. LS, least‐squares; s.e., standard error.