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Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomized phase III study.

ABSTRACT: To examine the efficacy and safety of once-weekly dulaglutide monotherapy (0.75?mg) compared with placebo and once-daily liraglutide (0.9?mg) in Japanese patients with type 2 diabetes.This was a phase III, 52-week (26-week primary endpoint), randomized, double-blind, placebo-controlled, open-label comparator (liraglutide) trial comparing 492 Japanese patients with type 2 diabetes (dulaglutide, n?=?281; liraglutide, n?=?141; and placebo, n?=?70) who were aged ?20?years. Patients and investigators were blinded to treatment assignment for dulaglutide and placebo but not for liraglutide. The primary objective evaluated the superiority of dulaglutide versus placebo on change from baseline in glycated haemoglobin (HbA1c) at 26?weeks. Analyses were performed on the full analysis set.At 26?weeks, once-weekly dulaglutide was superior to placebo and non-inferior to once-daily liraglutide for HbA1c change from baseline [least squares mean difference: dulaglutide vs placebo -1.57% (95% confidence interval -1.79 to -1.35); dulaglutide vs liraglutide -0.10% (95% confidence interval -0.27 to 0.07)]. The most frequently reported adverse events were nasopharyngitis, constipation, diarrhoea, nausea, abdominal distension and decreased appetite; only decreased appetite was different between the dulaglutide and liraglutide groups [dulaglutide, n?=?2 (0.7%); liraglutide, n?=?8 (5.8%); p?=?0.003]. Nine (1.8%) patients experienced hypoglycaemia [dulaglutide, n?=?6 (2.1%); liraglutide, n?=?2 (1.5%); placebo, n?=?1 (1.4%)], with no event being severe.In Japanese patients with type 2 diabetes, once-weekly dulaglutide (0.75?mg) was superior to placebo and non-inferior to once-daily liraglutide (0.9?mg) for reduction in HbA1c at 26?weeks. Dulaglutide was safe and well tolerated.

SUBMITTER: Miyagawa J

PROVIDER: S-EPMC5042083 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomized phase III study.

Miyagawa J J Odawara M M Takamura T T Iwamoto N N Takita Y Y Imaoka T T

Diabetes, obesity & metabolism 20150820 10

<h4>Aims</h4>To examine the efficacy and safety of once-weekly dulaglutide monotherapy (0.75 mg) compared with placebo and once-daily liraglutide (0.9 mg) in Japanese patients with type 2 diabetes.<h4>Methods</h4>This was a phase III, 52-week (26-week primary endpoint), randomized, double-blind, placebo-controlled, open-label comparator (liraglutide) trial comparing 492 Japanese patients with type 2 diabetes (dulaglutide, n = 281; liraglutide, n = 141; and placebo, n = 70) who were aged ≥20 year ...[more]

PMID: 26179187

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Project description:Objective:To evaluate the effects of once-weekly dulaglutide injection and once-daily glimepiride on glucose fluctuation in patients with type 2 diabetes mellitus (T2DM) using the Continuous Glucose Monitoring System (CGMS). Methods:A total of 23 patients with T2DM were randomly assigned into two groups for 26 weeks: the dulaglutide group (n = 13) and the glimepiride group (n = 10). 72-hour CGMS was applied to all patients: before and after the treatment. General clinical data were collected and measured, such as fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), tumor necrosis factor-? (TNF-?), 8-iso-prostaglandin F2? (8-iso-PGF2?), and interleukin-6 (IL-6). Results:HbA1c of the dulaglutide group was reduced from 8.38 ± 0.93% to 6.68 ± 0.73% after the treatment (P < 0.05); similarly, it was reduced from 7.91 ± 0.98% to 6.67 ± 0.74% (P < 0.05) in the glimepiride group. The levels of serum 8-iso-PGF2?, TNF-?, and IL-6 all decreased significantly in both groups after treatment, and there was no significant difference found between the two groups (P > 0.05). The Mean Blood Glucose (MBG) of the two groups declined significantly after therapy (P < 0.05). However, the Standard Deviation of Blood Glucose (SDBG) decreased significantly only in the dulaglutide group (from 2.57 ± 0.74 mmol/L to 1.98 ± 0.74 mmol/L, P < 0.05). There were no significant changes of Mean Amplitude of Glycemic Excursion (MAGE) and Absolute Means of Daily Difference (MODD) after treatment in both groups. Furthermore, no statistically significant difference was found between the two groups in MBG, SDBG, MAGE, and MODD (P > 0.05). The percentage time (PT) (>10?mmol/L and 3.9-10?mmol/L) of the two groups was significantly changed after the treatment (P < 0.05). However, this was not seen in the PT < 3.9 mmol/L after the treatment (P > 0.05). Conclusion:Once-weekly dulaglutide injection has the same effectiveness as daily glimepiride on lowering blood glucose and decreasing oxidation stress and inflammation and is more effective in controlling glucose fluctuation as compared with glimepiride. This trial is registered with ClinicalTrials.gov NCT01644500.

Project description:IntroductionOnce-weekly semaglutide 1 mg is a novel glucagon-like peptide 1 receptor agonist (GLP-1 RA) that, in the SUSTAIN clinical trials, has demonstrated greater reductions in glycated haemoglobin (HbA1c) and body weight than the other GLP-1 RAs exenatide extended-release (ER) 2 mg, dulaglutide 1.5 mg and liraglutide 1.2 mg. The aim of this analysis was to evaluate the relative cost of control of achieving treatment goals in people with type 2 diabetes (T2D) treated with once-weekly semaglutide versus exenatide ER, dulaglutide and liraglutide from a UK perspective.MethodsProportions of patients reaching HbA1c targets (< 7.0% and < 7.5%), weight loss targets (≥ 5% reduction in body weight) and composite endpoints (HbA1c < 7.0% without weight gain or hypoglycaemia; reduction in HbA1c of ≥ 1% and weight loss of ≥ 5%) were obtained from the SUSTAIN clinical trials. Annual per patient treatment costs were based on wholesale acquisition costs from July 2019 in the UK. Cost of control was calculated by plotting relative treatment costs against relative efficacy.ResultsThe annual per patient cost was similar for all GLP-1 RAs. Once-weekly semaglutide was superior to exenatide ER, dulaglutide and liraglutide in bringing patients to HbA1c and weight loss targets, and to composite endpoints. When looking at the composite endpoint of HbA1c < 7.0% without weight gain or hypoglycaemia, exenatide ER, dulaglutide and liraglutide were 50.0%, 21.6% and 51.3% less efficacious in achieving this, respectively, than once-weekly semaglutide. Consequently, the efficacy-to-cost ratios for once-weekly semaglutide were superior to all comparators in bringing patients to all endpoints.ConclusionsThe present study showed that once-weekly semaglutide offers superior cost of control versus exenatide ER, dulaglutide and liraglutide in terms of achieving clinically relevant, single and composite endpoints. Once-weekly semaglutide 1 mg would therefore represent good value for money in the UK setting.

Project description:BACKGROUND:Dulaglutide is a new, long-acting glucagon-like peptide analogue in the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg, given by injection once weekly. This systematic review reports the effectiveness and safety of dulaglutide in type 2 diabetes in dual and triple therapy. METHODS:MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and conference abstracts were searched from 2005 to August 2014, and updated in January 2015. Company websites and references of included studies were checked for potentially relevant studies. European Medicines Agency and US Food and Drug Administration websites were searched. RESULTS:Four trials were included. All were manufacturer-funded randomized controlled trials from the Assessment of Weekly Administration of Dulaglutide in Diabetes (AWARD) program. AWARD-1 compared dulaglutide 1.5 mg against exenatide 10 µg twice daily and placebo, AWARD-2 compared dulaglutide 0.75 and 1.5 mg against insulin glargine, AWARD-5 compared dulaglutide 0.75 and 1.5 mg against sitagliptin 100 mg and placebo, and AWARD-6 compared dulaglutide 1.5 mg against liraglutide 1.8 mg. The duration of follow-up in the trials ranged from 26 to 104 weeks. The primary outcome of all the included trials was change in HbA1c. At 26 weeks, greater HbA1c reductions were seen with dulaglutide than with twice daily exenatide (dulaglutide 1.5/0.75 mg: -1.5%/-1.3%; exe: 0.99%) and sitagliptin (1.5/0.75 mg -1.22%/-1.01%; sitagliptin: -0.6%). HbA1c change was greater with dulaglutide 1.5 mg (-1.08%) than with glargine (-0.63%), but not with dulaglutide 0.75 mg (-0.76%). Dulaglutide 1.5 mg was found to be noninferior to liraglutide 1.8 mg. More patients treated with dulaglutide achieved HbA1c targets of <7% and ≤6.5%. Reduction in weight was greater with dulaglutide than with sitagliptin and exenatide. Hypoglycemia was infrequent. The main adverse events were nausea, diarrhea, and vomiting. CONCLUSION:Dulaglutide is effective in the treatment of patients with type 2 diabetes but we need long follow-up data for safety concerns.

Project description:BackgroundType 2 Diabetes Mellitus (T2DM) is a highly prevalent disease worldwide and in Colombia, representing one of the main causes of death and placing a considerable burden on healthcare systems. 13 classes of drugs are approved for the treatment of T2DM, with Glucagon-like Peptide-1 (GLP-1) receptor agonists being a first-line treatment option for patients with or at high risk of certain cardiovascular diseases and chronic kidney disease. The objective of this study is to conduct a short-term cost-effectiveness analysis of once-weekly semaglutide versus once-weekly dulaglutide in Colombian adults with T2DM, from a third-party payer perspective.MethodsNumbers needed to treat were calculated for different single and composite endpoints of the SUSTAIN 7 trial, annual costs for once weekly semaglutide 1.0 mg and dulaglutide 1.5 mg were extracted from the public SISMED database. With these inputs a cost of control model was developed, to obtain the annual cost of bringing one T2DM patient to relevant clinical outcomes by using semaglutide or dulaglutide.ResultsSemaglutide was considered cost-effective compared to dulaglutide across all pre-specified endpoints, even in the different scenarios evaluated in the sensitivity analyses, and in a particularly pronounced manner for weight loss outcomes. Semaglutide at a dose of 1.0 mg once-weekly was cost-effective compared to dulaglutide 1.5 mg across all outcomes in the short-term, making it an appropriate first-line choice in the treatment of T2DM when deciding between these two GLP-1 receptor agonists.ConclusionsThis is the first short-term cost-effectiveness study of semaglutide and dulaglutide in T2DM Colombian patients. Our modeled results suggest that once-weekly semaglutide represents a cost-effective option for treating individuals with T2DM in Colombia who are not achieving glycaemia control with metformin, and it would be expected to improve HbA1C, promote greater weight loss and reduce costs from a third-payer perspective compared with treatment with dulaglutide.

Project description:IntroductionOnce-weekly semaglutide is a novel glucagon-like peptide-1 (GLP-1) analog for the treatment of type 2 diabetes (T2D) that has been associated with greater reductions in glycated hemoglobin (HbA1c) and body weight versus GLP-1 receptor agonists dulaglutide, exenatide extended-release (ER), liraglutide and lixisenatide in the SUSTAIN trial program and a network meta-analysis (NMA). The aim of the present study was to assess the long-term cost-effectiveness of semaglutide versus all available GLP-1 receptor agonists in Denmark, using a clinically orientated treatment approach.MethodsOutcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline characteristics and treatment effects were sourced from the corresponding SUSTAIN trials and the NMA. Patients were assumed to initiate GLP-1 receptor agonist therapy and subsequently treatment-intensify according to clinical treatment guidelines, with addition of basal insulin and switching to basal-bolus insulin occurring when HbA1c exceeded recommended targets. Patients were assumed to receive a GLP-1 receptor agonist plus basal insulin therapy once HbA1c levels reached 7.5% and a basal-bolus insulin regimen once HbA1c exceeded 8.0%. Costs were captured in 2017 Danish kroner (DKK), with future costs and outcomes discounted at 3% per annum.ResultsPrimary analyses indicated that semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.11 and 0.34 quality-adjusted life years, respectively, versus dulaglutide, achieved at cost savings of DKK 289 and DKK 13,416, respectively. Supporting analyses indicated that both doses of semaglutide were either cost-effective or dominant versus exenatide ER, liraglutide 1.2 mg and 1.8 mg and lixisenatide.ConclusionSemaglutide represents a cost-effective alternative to other GLP-1 receptor agonist therapies available in Denmark, demonstrating clinical benefits versus dulaglutide, exenatide ER, liraglutide and lixisenatide for the treatment of patients with T2D.FundingNovo Nordisk A/S. Plain language summary available for this article.

Dataset Information

Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomized phase III study.

Publications

Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomized phase III study.

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