1. Placebo-controlled, randomized trial of the addition of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (AWARD-9).
- Author
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Pozzilli P, Norwood P, Jódar E, Davies MJ, Ivanyi T, Jiang H, Woodward DB, and Milicevic Z
- Subjects
- Aged, Diabetes Mellitus, Type 2 blood, Double-Blind Method, Drug Administration Schedule, Drug Monitoring, Drug Resistance, Drug Therapy, Combination, Female, Glucagon-Like Peptides administration & dosage, Glucagon-Like Peptides adverse effects, Glucagon-Like Peptides therapeutic use, Glycated Hemoglobin analysis, Humans, Hypoglycemia chemically induced, Hypoglycemia prevention & control, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents adverse effects, Immunoglobulin Fc Fragments administration & dosage, Immunoglobulin Fc Fragments adverse effects, Incretins administration & dosage, Incretins adverse effects, Injections, Subcutaneous, Insulin Glargine administration & dosage, Insulin Glargine adverse effects, Intention to Treat Analysis, Male, Middle Aged, Patient Dropouts, Recombinant Fusion Proteins administration & dosage, Recombinant Fusion Proteins adverse effects, Diabetes Mellitus, Type 2 drug therapy, Glucagon-Like Peptide-1 Receptor antagonists & inhibitors, Glucagon-Like Peptides analogs & derivatives, Hyperglycemia prevention & control, Hypoglycemic Agents therapeutic use, Immunoglobulin Fc Fragments therapeutic use, Incretins therapeutic use, Insulin Glargine therapeutic use, Recombinant Fusion Proteins therapeutic use
- Abstract
Aim: To compare the addition of weekly dulaglutide vs the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub-optimum glycated haemoglobin (HbA1c) concentration., Materials and Methods: Patients (N = 300) from this phase III, double-blind, parallel-arm, placebo-controlled study were randomized to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± standard deviation baseline dose: 39 ± 22 U), with or without metformin (≥1500 mg/d). The primary endpoint was superiority of dulaglutide/glargine to placebo/glargine with regard to change from baseline in HbA1c level at 28 weeks., Results: Least squares (LS) mean ± standard error (s.e.) HbA1c changes from baseline were -1.44 ± 0.09% (-15.74 ± 0.98 mmol/mol) with dulaglutide/glargine and -0.67 ± 0.09% (-7.32 ± 0.98 mmol/mol) with placebo/glargine at 28 weeks (LS mean difference [95% confidence interval] -0.77% [-0.97, -0.56]; P < .001). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: -2.41 ± 0.39 kg; P < .001). Increases from baseline in mean glargine dose were significantly smaller with dulaglutide/glargine vs placebo/glargine (13 ± 2 U [0.1 ± 0.02 U/kg] vs 26 ± 2 U [0.3 ± 0.02 U/kg], respectively; P < .001; LS mean ± s.e. final dose: dulaglutide/glargine, 51 ± 2 U; placebo/glargine, 65 ± 2 U). The hypoglycaemia rate (≤3.9 mmol/L threshold) was 7.69 ± 15.15 and 8.56 ± 16.13 events/patient/year, respectively (P = .488). One episode of severe hypoglycaemia occurred in the dulaglutide/glargine group. Common gastrointestinal adverse events with dulaglutide were nausea (12.0%), diarrhoea (11.3%) and vomiting (6.0%)., Conclusions: Weekly dulaglutide 1.5 mg added to basal insulin is an efficacious and well tolerated treatment option for patients with T2D., (© 2017 John Wiley & Sons Ltd.) more...
- Published
- 2017
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