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Dulaglutide: an evidence-based review of its potential in the treatment of type 2 diabetes.

ABSTRACT: INTRODUCTION:As the prevalence of type 2 diabetes mellitus (T2DM) is anticipated to continue to rise worldwide, so too are the treatment options also continuing to expand. Current guidelines recommend individualized treatment plans which allow for provider choice and diversity of pharmacotherapeutic regimens. The glucagon-like peptide-1 receptor agonist (GLP-1 RA) class is rapidly expanding, with dulaglutide (Trulicity™) as a once-weekly agent recently approved. AIMS:This article examines the evidence currently available on the efficacy and safety of dulaglutide for use in T2DM. EVIDENCE REVIEW:Dulaglutide has been shown to have similar efficacy and safety to other newer GLP-1 RAs, and better glycemic control than placebo. It lowers glycated hemoglobin (A1c), fasting and postprandial glucose levels, and promotes weight loss when used as first-, second-, or third-line therapy. It has also been shown to improve ?-cell function and provide cardiovascular benefits, such as lower blood pressure and improved lipid levels. Dulaglutide also has a low risk for hypoglycemia and a similar adverse effect profile to other GLP-1 RAs in the class, with transient gastrointestinal problems and potential risk for pancreatitis. PLACE IN THERAPY:While long-term data on safety and efficacy are forthcoming, dulaglutide is positioned to be placed at the same level as other GLP-1 RAs in the class: as second-line therapy in addition to diet and exercise in those patients who cannot achieve glycemic control on monotherapy metformin. It may also be useful as first-line therapy instead of metformin. CONCLUSION:Dulaglutide is a once-weekly GLP-1 RA approved for the treatment of T2DM that has shown similar efficacy to other agents in this class.

SUBMITTER: Edwards KL

PROVIDER: S-EPMC4295897 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Dulaglutide: an evidence-based review of its potential in the treatment of type 2 diabetes.

Edwards Krystal L KL Minze Molly G MG

Core evidence 20150109

<h4>Introduction</h4>As the prevalence of type 2 diabetes mellitus (T2DM) is anticipated to continue to rise worldwide, so too are the treatment options also continuing to expand. Current guidelines recommend individualized treatment plans which allow for provider choice and diversity of pharmacotherapeutic regimens. The glucagon-like peptide-1 receptor agonist (GLP-1 RA) class is rapidly expanding, with dulaglutide (Trulicity™) as a once-weekly agent recently approved.<h4>Aims</h4>This article ...[more]

PMID: 25657615

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Project description:IntroductionRandomized controlled trials (RCTs) have demonstrated the efficacy of dulaglutide in adults with type 2 diabetes mellitus (T2DM), but results may not be generalizable in routine practice. This pragmatic literature review aimed to summarize real-world evidence (RWE) for dulaglutide.MethodsThe MEDLINE, EMBASE, NHS Economic Evaluation Database, and Health Technology Assessment databases were searched from January 2014 to July 2019 for studies providing RWE for dulaglutide in adults with T2DM regarding at least one outcome of interest (change in glycated hemoglobin [HbA1c]; weight; adherence; persistence; discontinuation; costs; healthcare resource utilization; health-related quality of life; patient satisfaction; and preference). Relevant congress abstracts were identified from EMBASE.ResultsA total of 29 studies (11 articles; 18 abstracts) were included. RWE for dulaglutide was not identified for all outcomes of interest. Dulaglutide reduced HbA1c from baseline to 3-24 months by 0.5-2.2% across studies (n = 20), and 23.4-55.7% of patients achieved HbA1c < 7.0%. Weight was reduced by 2.1-6.4 kg across studies of 3-12 months (n = 15). Based on outcomes from ten studies, 27.2-61.0% of dulaglutide patients were adherent. Mean persistence was 146-152 days and > 250 days in 6- and 12-month studies, respectively. Most studies reported discontinuation rates of 26.2-37.0%. Adherence and persistence were consistently reported to be greater in dulaglutide-treated patients in RW settings compared with other glucagon-like peptide-1 receptor agonists. Dulaglutide was associated with lower costs per 1% reduction in HbA1c compared with exenatide, liraglutide, or basal insulin (n = 3 studies).ConclusionEvidence from RWE studies suggests that dulaglutide may be associated with clinically relevant reductions in HbA1c, with a favorable adherence, persistence, and discontinuation profile in patients with T2DM in routine clinical practice. These findings provide additional insights regarding the potential value of dulaglutide in real-world settings that may assist healthcare decision makers in the delivery of patient-centered care.

Project description:BackgroundThe REWIND trial demonstrated cardiovascular (CV) benefits to patients with type 2 diabetes and multiple CV risk factors or established CV disease. This exploratory analysis evaluated the degree to which the effect of dulaglutide on CV risk factors could statistically account for its effects on major adverse cardiovascular events (MACE) in the REWIND trial.MethodsPotential mediators of established CV risk factors that were significantly reduced by dulaglutide were assessed in a post hoc analysis using repeated measures mixed models and included glycated hemoglobin (HbA1c), body weight, waist-to-hip ratio, systolic blood pressure, low-density lipoprotein (LDL), and urine albumin/creatinine ratio (UACR). These factors, for which the change in level during follow-up was significantly associated with incident MACE, were identified using Cox regression modeling. Each identified variable was then included as a covariate in the Cox model assessing the effect of dulaglutide on MACE to estimate the degree to which the hazard ratio of dulaglutide vs placebo was attenuated. The combined effect of the variables associated with attenuation was assessed by including all variables in an additional Cox model.ResultsAlthough all evaluated variables were significantly improved by treatment, only changes in HbA1c and UACR were associated with MACE and a reduction in the effect of dulaglutide on this outcome was observed. The observed hazard ratio for MACE for dulaglutide vs placebo reduced by 36.1% by the updated mean HbA1c, and by 28.5% by the updated mean UACR. A similar pattern was observed for change from baseline in HbA1c and UACR and a reduction of 16.7% and 25.4%, respectively in the hazard ratio for MACE with dulaglutide vs placebo was observed. When HbA1c and UACR were both included, the observed hazard ratio reduced by 65.4% for the updated mean and 41.7% for the change from baseline with no HbA1c-UACR interaction (P interaction = 0.75 and 0.15, respectively).ConclusionsTreatment-induced improvement in HbA1c and UACR, but not changes in weight, systolic blood pressure, or LDL cholesterol, appear to partly mediate the beneficial effects of dulaglutide on MACE outcomes. These observations suggest that the proven effects of dulaglutide on cardiovascular disease benefit are partially related to changes in glycemic control and albuminuria, with residual unexplained benefit. Clinicaltrials.gov; Trial registration number: NCT01394952. URL: https://clinicaltrials.gov/ct2/show/NCT01394952.

Project description:IntroductionDulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), became available in Italy in April 2016. The aim of ANDREW (Active Notes on Dulaglutide in the REal World), a multicenter, prospective, observational study, was to evaluate glycemic control and weight (co-primary outcomes) for up to 24 months in the real-life setting in consecutive outpatients with type 2 diabetes (T2D) who initiated dulaglutide. Co-secondary outcomes were durability of treatment effects on both glycated hemoglobin (HbA1c) and body weight.MethodsOverall, 1584 subjects (696 women, 888 men) with T2D (mean age [± standard deviation] 61.7 ± 10.2 years; mean T2D duration 9.9 ± 6.9 years) were treated with dulaglutide (0.75 or 1.5 mg once weekly) between April 2016 and December 2019.ResultsA total of 1130 patients completed 12 months of follow-up, while 170 patients interrupted treatment before the 12-month endpoint. At 12 months, average HbA1c and average fasting plasma glucose (FPG) were significantly lower compared to baseline levels (- 10 mmol/mol and - 24.9 mg/dL, respectively), as were body weight (- 3.4 kg) and waist circumference (- 3.3 cm) values (all p < 0.0001). Among subjects that completed 24 months of follow-up (n = 270), the rapid decline in HbA1c and FPG values in the first 12 months was followed by stabilization in the following 12 months (p value for 12-24 months trend: 0.4 and 0.6, respectively).ConclusionsDulaglutide is an effective drug for the treatment of T2D that is administered once weekly using a simple auto-injector device. Real-life data confirm the observations in randomized controlled trials that persistent treatment with dulaglutide may help patients with T2D achieve an improvement in some metabolic features and in body weight. It is important that the benefits of therapy with dulaglutide, i.e., the effects of the "glycemic" and the so-called "extra-glycemic" actions of GLP-1RAs, are supported by diabetes care teams emphasizing the need for patients to maintain a healthy lifestyle.

Project description:IntroductionIn the randomized, open-label, parallel-arm, active-controlled phase III AWARD-CHN2 trial, once-weekly dulaglutide plus concomitant oral antihyperglycemic medications (OAMs) improved HbA1c over 26 weeks compared with once-daily insulin glargine in patients with type 2 diabetes mellitus (T2DM). This post-hoc subgroup analysis of AWARD-CHN2 investigated the pancreatic safety of dulaglutide in Chinese patients with T2DM, stratified by potential influencing factors.MethodsChanges in pancreatic enzyme (pancreatic amylase, total amylase, and lipase) levels over 26 weeks were assessed and stratified by patient age (< 60, ≥ 60 years), sex (female, male), duration of diabetes (< 10, ≥ 10 years), baseline weight (< 70, ≥ 70 kg), BMI (< 25, ≥ 25 kg/m2), HbA1c (< 8.5, ≥ 8.5%), triglycerides (< 2.3, ≥ 2.3 mmol/L), and concomitant OAMs (metformin, sulfonylurea, metformin plus sulfonylurea).ResultsA total of 203 Chinese patients with T2DM were included in this post-hoc analysis. Pancreatic enzyme levels increased within the normal range from baseline to Week 26, and no pancreatitis events were confirmed by independent adjudication. Least-squares mean increase in pancreatic amylase (U/L) from baseline to Week 26 was comparable across all subgroups with no statistically (all P-values > 0.05) or clinically significant between-group differences for age (< 60 years: 5.34; ≥ 60 years: 6.71), sex (female: 5.85; male: 5.66), duration of diabetes (< 10 years: 6.15; ≥ 10 years: 4.85), weight (< 70 kg: 6.19; ≥ 70 kg: 5.39), BMI (< 25 kg/m2: 5.92; ≥ 25 kg/m2: 5.61), HbA1c (< 8.5%: 6.82; ≥ 8.5%: 4.08), triglycerides (< 2.3 mmol/L: 4.94; ≥ 2.3 mmol/L: 8.04), and concomitant OAMs (metformin: 5.68; sulfonylurea: 5.44; metformin plus sulfonylurea: 5.87). Similar results were observed for total amylase and lipase.ConclusionIn Chinese patients with T2DM receiving dulaglutide 1.5 mg in AWARD-CHN2, elevations of pancreatic enzymes over 26 weeks were within the normal range and were neither associated with pancreatitis nor baseline factors, which suggests the clinical use of dulaglutide in Chinese patients with T2DM is not associated with pancreatic safety issues.Clinical trial registrationNCT01648582.

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Dulaglutide: an evidence-based review of its potential in the treatment of type 2 diabetes.

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Dulaglutide: an evidence-based review of its potential in the treatment of type 2 diabetes.

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