| 1. |
- Blonde, Lawrence, et al.
(författare)
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Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4) : a randomised, open-label, phase 3, non-inferiority study
- 2015
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Ingår i: The Lancet. - New York, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 385:9982, s. 2057-2066
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Tidskriftsartikel (refereegranskat)abstract
- Background: For patients with type 2 diabetes who do not achieve target glycaemic control with conventional insulin treatment, advancing to a basal-bolus insulin regimen is often recommended. We aimed to compare the efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide with that of insulin glargine, both combined with prandial insulin lispro, in patients with type 2 diabetes.Methods: We did this 52 week, randomised, open-label, phase 3, non-inferiority trial at 105 study sites in 15 countries. Patients (aged ≥18 years) with type 2 diabetes inadequately controlled with conventional insulin treatment were randomly assigned (1:1:1), via a computer-generated randomisation sequence with an interactive voice-response system, to receive once-weekly dulaglutide 1·5 mg, dulaglutide 0·75 mg, or daily bedtime glargine. Randomisation was stratified by country and metformin use. Participants and study investigators were not masked to treatment allocation, but were unaware of dulaglutide dose assignment. The primary outcome was a change in glycated haemoglobin A1c (HbA1c) from baseline to week 26, with a 0·4% non-inferiority margin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01191268.Findings: Between Dec 9, 2010, and Sept 21, 2012, we randomly assigned 884 patients to receive dulaglutide 1·5 mg (n=295), dulaglutide 0·75 mg (n=293), or glargine (n=296). At 26 weeks, the adjusted mean change in HbA1c was greater in patients receiving dulaglutide 1·5 mg (-1·64% [95% CI -1·78 to -1·50], -17·93 mmol/mol [-19·44 to -16·42]) and dulaglutide 0·75 mg (-1·59% [-1·73 to -1·45], -17·38 mmol/mol [-18·89 to -15·87]) than in those receiving glargine (-1·41% [-1·55 to -1·27], -15·41 mmol/mol [-16·92 to -13·90]). The adjusted mean difference versus glargine was -0·22% (95% CI -0·38 to -0·07, -2·40 mmol/mol [-4·15 to -0·77]; p=0·005) for dulaglutide 1·5 mg and -0·17% (-0·33 to -0·02, -1·86 mmol/mol [-3·61 to -0·22]; p=0·015) for dulaglutide 0·75 mg. Five (<1%) patients died after randomisation because of septicaemia (n=1 in the dulaglutide 1·5 mg group); pneumonia (n=1 in the dulaglutide 0·75 mg group); cardiogenic shock; ventricular fibrillation; and an unknown cause (n=3 in the glargine group). We recorded serious adverse events in 27 (9%) patients in the dulaglutide 1·5 mg group, 44 (15%) patients in the dulaglutide 0·75 mg group, and 54 (18%) patients in the glargine group. The most frequent adverse events, arising more often with dulaglutide than glargine, were nausea, diarrhoea, and vomiting.Iinterpretation: Dulaglutide in combination with lispro resulted in a significantly greater improvement in glycaemic control than did glargine and represents a new treatment option for patients unable to achieve glycaemic targets with conventional insulin treatment.FUNDING: Eli Lilly and Company.
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| 2. |
- Jendle, Johan, 1963-, et al.
(författare)
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Continuous glucose monitoring in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonist dulaglutide in combination with prandial insulin lispro : an AWARD-4 substudy
- 2016
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Ingår i: Diabetes, obesity and metabolism. - : Wiley-Blackwell Publishing Inc.. - 1462-8902 .- 1463-1326. ; 18:10, s. 999-1005
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insulin use with GLP-1 receptor agonists is of interest because of the potential for glucose lowering with reduced insulin dosing versus an insulin-only regimen. The AWARD-4 trial, designed to compare these regimens, included a sub-study using 24-hour continuous glucose monitoring (CGM).Methods: The AWARD-4 trial randomised 884 conventional insulin regimens-treated patients to dulaglutide 1.5 mg, 0.75 mg and glargine, all in combination with prandial insulin lispro. The CGM sub-study included 144 patients inserted with Medtronic CGMS® iPro™ CGM device to enable 3-day glucose monitoring. CGM sessions were completed at weeks 0, 13, 26, and 52. CGM measures included mean 24-hour glucose, percentage time in target glucose ranges, hyper- and hypoglycaemia, and glucose variability. The primary objective was treatment comparison for percentage time CGM glucose in the 3.9-7.8 mmol/L range after 26 weeks.Results: At week 26, mean CGM glucose decreased in all treatment groups (change from baseline -2.8 ± 0.3, -2.4 ± 0.3, and -2.5 ± 0.3 mmol/L for dulaglutide 1.5 mg, 0.75 mg, and glargine, respectively); between-group differences were not statistically significant. Treatment groups were similar for percentage time in 3.9-7.8 mmol/L range. Percentage time in 3.9-10.0 mmol/L range was greater for dulaglutide 1.5 mg than glargine (p < 0.05). Dulaglutide and glargine were associated with decreased glucose variability for all CGM variability indices. Overall within-patient SD was significantly reduced with dulaglutide 1.5 mg versus glargine (p < 0.05). At week 52, there were no significant differences between groups for measures of normoglycaemia or near-normoglycaemia and for the overall within-patient SD. Treatment with glargine was associated with greater increases in percentage time glucose was ≤3.9 mmol/L with statistically significant differences between the groups at 52 weeks (p < 0.05).Conclusions: In combination with prandial lispro, treatment with dulaglutide and glargine resulted in similar proportions of glucose values in the normoglycaemic range, but dulaglutide provided an improved balance between the proportion of values within the near-normoglycaemia range and values within the hypoglycaemic range.
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