Dulaglutide 1.5 mg as an add-on option for patients uncontrolled on insulin: Subgroup analysis by age, duration of diabetes and baseline glycated haemoglobin concentration

Kevin M Pantalone, Hiren Patel, Maria Yu, Laura Fernández Landó, Kevin M Pantalone, Hiren Patel, Maria Yu, Laura Fernández Landó

Abstract

Aims: To assess efficacy and safety of dulaglutide 1.5 mg combined with insulin, categorized by subgroups of baseline glycated haemoglobin (HbA1c; ≤9% and >9% [≤74.9 and >74.9 mmol/mol]), age (<65 and ≥65 years), and duration of diabetes (<10 and ≥10 years) at 6 months in patients with type 2 diabetes (T2D).

Materials and methods: This pooled analysis was conducted in a population of patients with T2D with similar baseline characteristics who were included in the AWARD-4 and AWARD-9 clinical trials and randomized to dulaglutide 1.5 mg (pooled mean baseline age 59 years, duration of diabetes 13 years, HbA1c 8.4% [68.3 mmol/mol]). Weight and hypoglycaemia were analysed by individual trial. In AWARD-4, dulaglutide plus lispro three times daily was assessed against glargine plus lispro three times daily. In AWARD-9, dulaglutide added to glargine was assessed against placebo added to glargine. Insulins were titrated to target in both trials.

Results: A total of 445 patients were included in this analysis (73% with HbA1c ≤9%, 27% [≤74.9 mmol/mol] with HbA1c >9% [>74.9 mmol/mol]; 70% aged <65 years, 30% aged ≥65 years; 36% with duration of diabetes <10 years, 64% with duration of diabetes ≥10 years). At 6 months, dulaglutide 1.5 mg significantly reduced HbA1c in all subgroups (P < .001), with the highest reduction observed in patients with baseline HbA1c >9% (>74.9 mmol/mol) (range - 1.3% to -2.5% [-14.2 to -27.3 mmol/mol]). The incidence rates of documented symptomatic and severe hypoglycaemia were similar in all subgroups in both trials. The most common adverse events observed in each trial were gastrointestinal in nature.

Conclusion: Dulaglutide 1.5 mg combined with basal or prandial insulin is efficacious for patients with T2D irrespective of age, duration of diabetes or baseline HbA1c.

Trial registration: ClinicalTrials.gov NCT01191268 NCT02152371.

Keywords: GLP-1 receptor agonist; dulaglutide; type 2 diabetes.

Conflict of interest statement

K.P. has received research funding from Merck and Novo Nordisk, compensation for serving as a consultant from Eli Lilly, Novo Nordisk, Sanofi, and Merck, and honoraria (lecture bureau) from AstraZeneca, Novo Nordisk, Merck, and Sanofi. L.F.L., H.P. and M.Y. are employees and shareholders of Eli Lilly and Company.

© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Change from baseline in glycated haemoglobin (HbA1c) by subgroups at 6 months. Data are presented as least squares mean (95% CI); **P < .001 vs baseline
Figure 2
Figure 2
Change from baseline in glycated haemoglobin (HbA1c) at 6 months by individual study. Data are presented as LSM (95% CI); **P < 0.001 versus baseline; #P < 0.05 and ##P < 0.001 versus comparator. Insulin lispro was administered TID
Figure 3
Figure 3
Change from baseline in body weight at 6 months by individual study. Data are presented as LSM (95% CI); *P < 0.05 and **P < 0.001 versus baseline, #P < 0.05 and ##P < 0.001 versus comparator. Insulin lispro was administered TID

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