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 (<scp>AWARD</scp>‐9)

Pozzilli, Paolo; Norwood, Paul; Jódar, Esteban; Davies, Melanie J.; Iványi, T.; Jiang, Honghua; Woodward, D. Bradley; Miličević, Zvonko

doi:10.1111/dom.12937

Cited by 110 publications

(157 citation statements)

References 26 publications

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“…In the subset of patients with available HbA1c results, those initiating dulaglutide had a greater reduction in HbA1c from baseline. The HbA1c results observed for dulaglutide initiators in the present study are consistent with those in the AWARD programme, ie, 0.7% to 1.6% for the 0.75‐mg dose and 0.8% to 1.6% for the 1.5‐mg dose . In the AWARD‐6 trial, dulaglutide 1.5 mg was non‐inferior to liraglutide 1.8 mg, and both treatments lowered HbA1c by 1.4% from baseline at 26 weeks .…”

Section: Discussionsupporting

confidence: 85%

Adherence, persistence, glycaemic control and costs among patients with type 2 diabetes initiating dulaglutide compared with liraglutide or exenatide once weekly at 12‐month follow‐up in a real‐world setting in the United States

Mody

Huang

et al. 2019

Diabetes Obesity Metabolism

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Aims To evaluate adherence, persistence, glycaemic control and costs at 12‐month follow‐up for patients initiating dulaglutide versus liraglutide or exenatide once weekly. Materials and methods The present retrospective observational claims study included patients with type 2 diabetes (T2D) and ≥ 1 pharmacy claim for dulaglutide, liraglutide or exenatide once weekly from the HealthCore Integrated Research Database. Adherence was defined as proportion of days covered ≥80%, and persistence was measured by time to discontinuation of index therapy. Change from baseline in glycated haemoglobin (HbA1c) concentration was assessed in a subset with pre‐ and post‐index HbA1c results. Propensity scores were used to match the cohorts. Results The baseline characteristics were balanced for the matched cohorts, dulaglutide versus liraglutide (n = 2471) and dulaglutide versus exenatide once weekly (n = 1891). Among those initiating dulaglutide there was a significantly higher proportion of adherent patients compared with the groups initiating liraglutide (51.2% vs. 38.2%; P < 0.001) and exenatide once weekly (50.7% vs. 31.9%; P < 0.001). At 12 months, 55% of patients in the dulaglutide group versus 43.8% in the liraglutide group (P < 0.001), and 54.9% in the dulaglutide versus 34.4% in the exenatide once‐weekly group (P < 0.001) were persistent. The dulaglutide group had a significantly greater reduction in HbA1c than the liraglutide group (−34.24 vs. −31.94 mmol/mol; P = 0.032), and a greater, but nonsignificant, reduction in HbA1c than the exenatide once‐weekly group (−34.46 vs. −31.94 mmol/mol; P = 0.056). The diabetes‐related total costs were not significantly different between the dulaglutide and the liraglutide group ($16,174 vs. $16,694; P = 0.184), and were significantly higher for dulaglutide than for exenatide once weekly ($15,768 vs. $14,615; P = 0.005). Conclusions Adherence and persistence are important considerations in patient‐centric treatment selection for patients with T2D. Higher adherence and persistence for dulaglutide compared with liraglutide or exenatide once weekly are relevant criteria when choosing glucagon‐like peptide‐1 receptor agonist treatment for patients with T2D.

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Section: Discussionsupporting

confidence: 85%

Adherence, persistence, glycaemic control and costs among patients with type 2 diabetes initiating dulaglutide compared with liraglutide or exenatide once weekly at 12‐month follow‐up in a real‐world setting in the United States

Mody

Huang

et al. 2019

Diabetes Obesity Metabolism

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“…It is possible that more adverse events occurred than were reported. These preliminary data support the idea that the addition of a GLP‐1 receptor agonist to basal insulin is an effective and safe therapeutic strategy to glycaemic control, as demonstrated in previous clinical trials . This study complements results reported in DURATION‐7, which was a large‐scale randomized trial; however, the utility of the results reported here indicates that in a real‐world clinical setting, once‐weekly exenatide is safe and efficacious.…”

Section: Discussionsupporting

confidence: 86%

“…There was 47% less documented symptomatic hypoglycaemia in the GLP‐1 group compared with the prandial insulin group in the HARMONY 6 study and a reported 87% decrease in hypoglycaemia with GLP‐1 therapy vs prandial insulin in the BEGIN: Victoza Add‐On study . In AWARD‐9, total hypoglycaemia was similar between the two treatment arms (dulaglutide/basal insulin: 54.7%; placebo/basal insulin: 50.7%) . Minor and confirmed non‐nocturnal hypoglycaemia occurred less frequency with twice‐daily exenatide in the 4B study compared with prandial insulin (30% vs 41%; 15% vs 34%, respectively) …”

Section: Discussionmentioning

confidence: 96%

“…At 26 weeks, HbA 1c was reduced by 0.74% in the liraglutide group compared with −0.39% in the insulin aspart group ( P = .0024). AWARD‐9 was a multicentre, double‐blind, parallel‐arm, placebo‐controlled study which compared once‐weekly dulaglutide in addition to insulin glargine to placebo plus insulin glargine . After 28 weeks, patients’ HbA 1c in the dulaglutide arm decreased by 1.44% and those in the placebo arm decreased by 0.67% ( P < .001).…”

Section: Discussionmentioning

confidence: 99%

“…Use of liraglutide in the BEGIN: Victoza Add‐On study was associated with a 6.1 pound (2.8 kg) decrease in weight compared with a 2 pound weight gain in the insulin aspart group . Pozzilli et al reported a 4.2 pound (1.9 kg) weight loss and a 1.1 pound (0.5 kg) weight gain in the dulaglutide and placebo arms, respectively, in AWARD‐9 . Diamant et al reported a 5.5 pound (2.5 kg) weight loss with twice‐daily exenatide and a 4.6 pound (2.1 kg) weight gain with thrice‐daily insulin lispro in the 4B study ( P < .001) …”

Section: Discussionmentioning

confidence: 99%

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A real‐world, observational study of weekly exenatide added to basal insulin in patients with type 2 diabetes mellitus (NCT02895672)

Stryker

Kane

Busch

2017

Endocrino Diabet & Metabol

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SummaryAim: This is a pre-post observational study from an endocrinology ambulatory care practice which assessed the effectiveness and safety following the addition of a glucagon-like peptide-1 (GLP-1) agonist, weekly exenatide (Bydureon), to basal insulin therapy in patients with type 2 diabetes mellitus (T2DM). Liraglutide plus basal insulin served as a comparison group. Materials and methods:A data collection form was utilized to collect study-related information. The primary study outcome was change in HbA 1c from baseline to 12 months after GLP-1 receptor agonist therapy was added to basal insulin therapy. Secondary outcomes were change in weight, percentage of patients achieving anHbA 1c of <7% (53 mmol/mol) or ≤6.5% (48 mmol/mol) and changes in blood pressure and lipid parameters. Safety was assessed by a collection of reported adverse events.Results: One-hundred and fifty patients met inclusion criteria (seventy-five per treatment arm). After 1 year of therapy, HbA 1c decreased by 0.7% in the entire cohort (onceweekly exenatide: −0.7%; once-daily liraglutide: −0.8%; no significant between-group difference). More subjects in the weekly exenatide arm achieved an HbA 1c < 7% (53 mmol/mol) (P = .03), but a comparable number achieved an HbA 1c ≤ 6.5% (48 mmol/ mol). Although significantly more patients achieved an HbA 1c < 7% (53 mmol/mol) in the once-weekly exenatide arm, the baseline HbA 1c was lower (7.9%) than the liraglutide arm (8.4%). No significant differences were observed between groups for other secondary outcomes. A similar number of subjects discontinued therapy, mainly due to gastrointestinal-ill effects, and hypoglycaemia incidence did not increase compared with the previous year. Conclusion:The addition of once-weekly exenatide to basal insulin was associated with appreciable reductions in HbA 1c and weight without an increase in hypoglycaemia. K E Y W O R D Sbasal insulin, exenatide, glucagon-like peptide-1 agonist, liraglutide

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Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes

Dahl

Onishi

Norwood³

et al. 2022

JAMA

Self Cite

320

437

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The effects of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as an addition to insulin glargine for treatment of type 2 diabetes have not been described. OBJECTIVE To assess the efficacy and safety of tirzepatide added to insulin glargine in patients with type 2 diabetes with inadequate glycemic control.DESIGN, SETTING, AND PARTICIPANTS Randomized phase 3 clinical trial conducted at 45 medical research centers and hospitals in 8 countries (enrollment from August 30, 2019, to March 20, 2020 follow-up completed January 13, 2021) in 475 adults with type 2 diabetes and inadequate glycemic control while treated with once-daily insulin glargine with or without metformin.INTERVENTIONS Patients were randomized in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of 5-mg (n = 116), 10-mg (n = 119), or 15-mg (n = 120) tirzepatide or volume-matched placebo (n = 120) over 40 weeks. Tirzepatide was initiated at 2.5 mg/week and escalated by 2.5 mg every 4 weeks until the assigned dose was achieved. MAIN OUTCOMES AND MEASURESThe primary end point was mean change from baseline in glycated hemoglobin A 1c (HbA 1c ) at week 40. The 5 key secondary end points included mean change in body weight and percentage of patients achieving prespecified HbA 1c levels. RESULTS Among 475 randomized participants (211 [44%] women; mean [SD] age, 60.6 [9.9] years; mean [SD] HbA 1c , 8.31% [0.85%]), 451 (94.9%) completed the trial. Treatment was prematurely discontinued by 10% of participants in the 5-mg tirzepatide group, 12% in the 10-mg tirzepatide group, 18% in the 15-mg tirzepatide group, and 3% in the placebo group. At week 40, mean HbA 1c change from baseline was −2.40% with 10-mg tirzepatide and −2.34% with 15-mg tirzepatide vs −0.86% with placebo (10 mg: difference vs placebo, −1.53% [97.5% CI, −1.80% to −1.27%]; 15 mg: difference vs placebo, −1.47% [97.5% CI, −1.75% to −1.20%]; P < .001 for both). Mean HbA 1c change from baseline was −2.11% with 5-mg tirzepatide (difference vs placebo, −1.24% [95% CI, −1.48% to −1.01%]; P < .001]). Mean body weight change from baseline was −5.4 kg with 5-mg tirzepatide, −7.5 kg with 10-mg tirzepatide, −8.8 kg with 15-mg tirzepatide and 1.6 kg with placebo (5 mg: difference, −7.1 kg [95% CI, −8.7 to −5.4]; 10 mg: difference, −9.1 kg [95% CI, −10.7 to −7.5]; 15 mg: difference, −10.5 kg [95% CI, −12.1 to −8.8]; P < .001 for all). Higher percentages of patients treated with tirzepatide vs those treated with placebo had HbA 1c less than 7% (85%-90% vs 34%; P < .001 for all). The most common treatment-emergent adverse events in the tirzepatide groups vs placebo group were diarrhea (12%-21% vs 10%) and nausea (13%-18% vs 3%).CONCLUSIONS AND RELEVANCE Among patients with type 2 diabetes and inadequate glycemic control despite treatment with insulin glargine, the addition of subcutaneous tirzepatide, compared with placebo, to titrated insulin glargine resulted in statistically significant improvements in glycemic control after 40 weeks.

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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)

Cited by 110 publications

References 26 publications

Adherence, persistence, glycaemic control and costs among patients with type 2 diabetes initiating dulaglutide compared with liraglutide or exenatide once weekly at 12‐month follow‐up in a real‐world setting in the United States

Adherence, persistence, glycaemic control and costs among patients with type 2 diabetes initiating dulaglutide compared with liraglutide or exenatide once weekly at 12‐month follow‐up in a real‐world setting in the United States

A real‐world, observational study of weekly exenatide added to basal insulin in patients with type 2 diabetes mellitus (NCT02895672)

Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes

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