Dulaglutide

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Zvonko Milicevic - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and safety of an expanded Dulaglutide dose range a phase 2 placebo controlled trial in patients with type 2 diabetes using metformin
    Diabetes Obesity and Metabolism, 2019
    Co-Authors: Juan P. Frias, Alan G. Wynne, Dagmar Bartaskova, David A. Cox, Brad Woodward, Lai S. Tham, Beata Matyjaszekmatuszek, Zvonko Milicevic
    Abstract:

    AIMS Dulaglutide, a once weekly GLP-1 receptor agonist, is approved at two doses (1.5 and 0.75 mg) for treatment of type 2 diabetes (T2D). Two higher doses of Dulaglutide (3.0 and 4.5 mg) were evaluated for safety and efficacy to determine whether these doses warrant further study for improved control of glucose and body weight. MATERIALS AND METHODS This 18-week, double-blind, phase 2 trial randomized 318 patients with T2D using ≥1500 mg metformin, to receive subcutaneous injection of placebo (n = 82), Dulaglutide 1.5 mg (n = 81), Dulaglutide 3.0 mg (n = 79) or Dulaglutide 4.5 mg (n = 76). The primary objective was superiority of Dulaglutide doses over placebo in reduction of HbA1c at 18 weeks. Secondary objectives included superiority of Dulaglutide over placebo in change from baseline in body weight and fasting serum glucose (FSG) at 18 weeks. Investigational doses of Dulaglutide were compared to the 1.5 mg dose as an exploratory objective. RESULTS HbA1c reduction at 18 weeks was significantly greater with Dulaglutide vs placebo (placebo, -0.44% ± 0.10% [-4.8 ± 1.1 mmol/mol]; Dulaglutide 1.5 mg, -1.23% ± 0.10% [-13.5 ± 1.1 mmol/mol]; Dulaglutide 3.0 mg, -1.31% ± 0.10% [-14.3 ± 1.1 mmol/mol]; Dulaglutide 4.5 mg, -1.40% ± 0.10% [-15.3 ± 1.1 mmol/mol]; P < 0.001, each dose), as were changes in body weight (placebo, -1.6 ± 0.39 kg; Dulaglutide 1.5 mg, -2.8 ± 0.39 kg; Dulaglutide 3.0 mg, -3.9 ± 0.39 kg; Dulaglutide 4.5 mg, -4.1 ± 0.41 kg; P < 0.001, each dose). All three Dulaglutide doses significantly reduced FSG from baseline (1.5 mg, -36.2 ± 4.7 mg/dL [-2.0 ± 0.3 mmol/L]; 3.0 mg, -34.5 ± 4.5 mg/dL [-1.9 ± 0.3 mmol/L]; 4.5 mg, -38.0 ± 4.7 mg/dL [-2.1 ± 0.3 mmol/L]) vs placebo (-12.4 ± 4.5 mg/dL [-0.7 ± 0.3 mmol/L]) (P < 0.001, all). Safety profiles of the higher doses were consistent with the established safety profile for Dulaglutide. Gastrointestinal events were mostly mild to moderate, and was dose-related for nausea. CONCLUSION All three Dulaglutide doses were superior to placebo in improving glycaemic control and reducing body weight in participants with T2D using metformin. The potential for doses of Dulaglutide of 3.0 and 4.5 mg to provide additional glycaemic benefit and weight reduction with an acceptable safety profile, compared with the 1.5 mg dose, warrants further study in a phase 3 trial.

  • Efficacy and safety of an expanded Dulaglutide dose range: A phase 2, placebo-controlled trial in patients with type 2 diabetes using metformin.
    Diabetes obesity & metabolism, 2019
    Co-Authors: Juan P. Frias, Alan G. Wynne, Beata Matyjaszek-matuszek, Dagmar Bartaskova, David A. Cox, Brad Woodward, Lai S. Tham, Zvonko Milicevic
    Abstract:

    AIMS Dulaglutide, a once weekly GLP-1 receptor agonist, is approved at two doses (1.5 and 0.75 mg) for treatment of type 2 diabetes (T2D). Two higher doses of Dulaglutide (3.0 and 4.5 mg) were evaluated for safety and efficacy to determine whether these doses warrant further study for improved control of glucose and body weight. MATERIALS AND METHODS This 18-week, double-blind, phase 2 trial randomized 318 patients with T2D using ≥1500 mg metformin, to receive subcutaneous injection of placebo (n = 82), Dulaglutide 1.5 mg (n = 81), Dulaglutide 3.0 mg (n = 79) or Dulaglutide 4.5 mg (n = 76). The primary objective was superiority of Dulaglutide doses over placebo in reduction of HbA1c at 18 weeks. Secondary objectives included superiority of Dulaglutide over placebo in change from baseline in body weight and fasting serum glucose (FSG) at 18 weeks. Investigational doses of Dulaglutide were compared to the 1.5 mg dose as an exploratory objective. RESULTS HbA1c reduction at 18 weeks was significantly greater with Dulaglutide vs placebo (placebo, -0.44% ± 0.10% [-4.8 ± 1.1 mmol/mol]; Dulaglutide 1.5 mg, -1.23% ± 0.10% [-13.5 ± 1.1 mmol/mol]; Dulaglutide 3.0 mg, -1.31% ± 0.10% [-14.3 ± 1.1 mmol/mol]; Dulaglutide 4.5 mg, -1.40% ± 0.10% [-15.3 ± 1.1 mmol/mol]; P 

  • Dulaglutide treatment results in effective glycaemic control in latent autoimmune diabetes in adults lada a post hoc analysis of the award 2 4 and 5 trials
    Diabetes Obesity and Metabolism, 2018
    Co-Authors: Paolo Pozzilli, Zvonko Milicevic, Sherry Martin, Imre Pavo, R D G Leslie, Anne L Peters, Raffaella Buzzetti, Sudha S Shankar, Jeremie Lebrec, Nanette C Schloot
    Abstract:

    Aims Patients with a type-2-diabetes (T2D) phenotype positive for glutamic acid decarboxylase antibodies (GADA) represent the majority of cases of latent autoimmune diabetes of the adult (LADA). The GLP-1 receptor agonist Dulaglutide, recently introduced for treatment of T2D, has yet to be evaluated in LADA patients. Our primary objective was to evaluate the effect of Dulaglutide on glycaemic control (HbA1c) in GADA-positive LADA vs GADA-negative T2D patients. Methods A post-hoc analysis was performed using data from 3 randomized phase 3 trials (AWARD-2,-4,-5; patients with GADA assessment) which were part of the Dulaglutide clinical development programme in T2D. LADA patients were identified by GADA ≥5 IU/mL (ELISA). Changes in HbA1c during 12 months of treatment with Dulaglutide or comparator were analysed using mixed-effect model repeated measures. Results Of 2466 adults tested for GADA (Dulaglutide, 1710; glargine, 298; sitagliptin, 294; placebo, 164), 2278 (92.4%) were GADA-negative and 188 (7.6%) were GADA-positive, including 58 GADA-high patients (> 200 IU/mL) and 130 GADA-low patients (≤200 and ≥5 IU/mL). Overall, baseline parameters were comparable between the groups. Dulaglutide resulted in comparable HbA1c reductions in GADA-negative (LS mean change [95%CI], -1.09% [-1.15, -1.03]) and GADA-positive patients (-0.94% [-1.15, -0.72]) at 12 months. HbA1c reductions were numerically, but not statistically, significantly larger in GADA-low patients (-1.02% [-1.26, -0.78]) vs GADA-high patients (-0.72% [-1.21,-0.24]) at 12 months. Similar outcomes were observed at 3 and 6 months. Conclusions These data are the first to indicate that Dulaglutide was effective in reducing HbA1c in LADA patients.

  • Dulaglutide as add on therapy to sglt2 inhibitors in patients with inadequately controlled type 2 diabetes award 10 a 24 week randomised double blind placebo controlled trial
    The Lancet Diabetes & Endocrinology, 2018
    Co-Authors: Bernhard Ludvik, Juan P. Frias, Francisco J Tinahones, Julio Wainstein, Honghua Jiang, Kenneth E Robertson, Luisemilio Garciaperez, Bradley D Woodward, Zvonko Milicevic
    Abstract:

    Summary Background Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms. We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist Dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors, with or without metformin. Methods AWARD-10 was a phase 3b, double-blind, parallel-arm, placebo-controlled, 24-week study done at 40 clinical sites in Austria, Czech Republic, Germany, Hungary, Israel, Mexico, Spain, and the USA. Eligible adult patients (≥18 years) with inadequately controlled type 2 diabetes (HbA 1c concentration ≥7·0% [53 mmol/mol] and ≤9·5% [80 mmol/mol]), a BMI of 45 kg/m 2 or less, and taking stable doses (>3 months) of an SGLT2 inhibitor (with or without metformin) were randomly assigned (1:1:1) via an interactive web-response system to subcutaneous injections of either Dulaglutide 1·5 mg, Dulaglutide 0·75 mg, or placebo once per week for 24 weeks. Patients and investigators were masked to Dulaglutide and placebo assignment, and those assessing outcomes were masked to study drug assignment. The primary objective was to test for the superiority of Dulaglutide (1·5 mg or 0·75 mg) versus placebo for change in HbA 1c concentration from baseline at 24 weeks. All analyses were done in the intention-to-treat population, defined as all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02597049. Findings Between Dec 7, 2015, and Feb 3, 2017, 424 patients were randomly assigned to Dulaglutide 1·5 mg (n=142), Dulaglutide 0·75 mg (n=142), and placebo (n=140). One patient in the Dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug. The reduction in HbA 1c concentration at 24 weeks was larger in patients receiving Dulaglutide (least squares mean [LSM] for Dulaglutide 1·5 mg −1·34% [SE 0·06] or −14·7 mmol/mol [0·6]; Dulaglutide 0·75 mg −1·21% [0·06] or −13·2 mmol/mol [0·6]) than in patients receiving placebo (−0·54% [0·06] or −5·9 mmol/mol [0·6]; p vs placebo). The LSM differences were −0·79% (95% CI −0·97 to −0·61) or −8·6 mmol/mol (−10·6 to −6·7) for Dulaglutide 1·5 mg and −0·66% (−0·84 to −0·49) or −7·2 mmol/mol (−9·2 to −5·4) for Dulaglutide 0·75 mg (p vs seven [5%] in the Dulaglutide 0·75 mg group vs five [4%] in the placebo group), diarrhoea (eight [6%] vs 14 [10%] vs four [3%]), and vomiting (five [4%] vs four [3%] vs one [1%]) were more common with Dulaglutide than with placebo. One episode of severe hypoglycaemia was reported in the Dulaglutide 0·75 mg group. Two (1%) patients receiving Dulaglutide 1·5 mg died, but these deaths were not considered to be related to study drug; no deaths occurred in the other groups. Interpretation Dulaglutide as add-on treatment to SGLT2 inhibitors (with or without metformin) resulted in significant and clinically relevant improvements in glycaemic control, with acceptable tolerability that is consistent with the established safety profile of Dulaglutide. Funding Eli Lilly and Company.

  • Efficacy and Safety of an Expanded Dulaglutide Dose Range—A Phase 2, Placebo-Controlled Trial in T2D Patients on Metformin
    Diabetes, 2018
    Co-Authors: Juan P. Frias, Alan G. Wynne, Beata Matyjaszek-matuszek, Dagmar Bartaskova, David A. Cox, Brad Woodward, Zvonko Milicevic
    Abstract:

    Dulaglutide is approved at two doses (0.75 and 1.5 mg) for treatment of T2D. There has been limited assessment of higher doses. We hypothesized that higher doses of Dulaglutide may provide further improvement in glucose and body weight control. In this study, 3 and 4.5 mg doses were evaluated for safety/efficacy after 18 weeks (weeks) of treatment, including a 6 week dose escalation. Patients (N=318) on ≥1500 mg metformin, were randomized (1:1:1:1) to placebo (n=82), Dulaglutide 1.5 mg (n=81), Dulaglutide 3 mg (n=79), Dulaglutide 4.5 mg (n=76). The primary objective was superiority of Dulaglutide doses over placebo in HbA1c reduction at 18 weeks. Table 1 presents the primary and selected secondary efficacy data. Reductions in HbA1c and body weight were significant for each dose vs. placebo. Incidence of gastrointestinal events (mostly mild to moderate) were dose-dependent for nausea (placebo, 4.9%; Dulaglutide 1.5 mg, 22.2%; Dulaglutide 3 mg, 24.1%; Dulaglutide 4.5 mg, 30.3%) but not for vomiting (placebo 4.9%; Dulaglutide 1.5 mg, 11.1%; Dulaglutide 3 mg, 10.1%; Dulaglutide 4.5 mg, 13.2%). No patients experienced severe hypoglycemia. The results of this trial show that 3 mg and 4.5 mg doses, compared to the 1.5 mg dose, may provide additional glycemic benefit and weight reduction with an acceptable safety profile in treatment of T2D patients, providing support for further phase 3 development. Disclosure J.P. Frias: Research Support; Self; AbbVie Inc., Allergan, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company. Consultant; Self; CeQur Corporation. Research Support; Self; Cirius Therapeutics, AstraZeneca, Calibra Medical, Elcelyx Therapeutics, Inc.. Consultant; Self; Elcelyx Therapeutics, Inc.. Research Support; Self; Eli Lilly and Company, Genentech, Inc., Ionis Pharmaceuticals, Inc., ICON plc., Janssen Pharmaceuticals, Inc.. Consultant; Self; Johnson & Johnson Diabetes Institute, LLC.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc.. Consultant; Self; Ligand Pharmaceuticals, Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc., Sanofi. Consultant; Self; Sanofi. Speaker9s Bureau; Self; Sanofi. Research Support; Self; Theracos, Inc.. A.G. Wynne: None. B. Matyjaszek-Matuszek: None. D. Bartaskova: None. D. Cox: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. B. Woodward: Employee; Self; Eli Lilly and Company. G. Li: Employee; Self; Eli Lilly and Company. Z. Milicevic: Employee; Self; Eli Lilly and Company.

Fady T Botros - One of the best experts on this subject based on the ideXlab platform.

  • Effects of Dulaglutide and Insulin Glargine on Estimated Glomerular Filtration Rate in a Real-world Setting
    Clinical therapeutics, 2018
    Co-Authors: Kristina S. Boye, Fady T Botros, Reema Mody, Maureen J. Lage, Brad Woodward
    Abstract:

    Abstract Purpose The aims of this study were to use real-world treatment results to compare changes in estimated glomerular filtration rate (eGFR) and glycosylated hemoglobin (HbA1c) among patients with type 2 diabetes who initiated treatment with Dulaglutide or insulin glargine and to determine the proportions of patients with renal impairment who initiate each treatment. Methods The study used data from the Practice Fusion electronic health records database from October 2013 through June 2017. Adults with type 2 diabetes who initiated Dulaglutide or insulin glargine therapy and had multiple recorded serum creatinine and/or HbA1c laboratory test results were included in the study. The Dulaglutide cohort (n = 1222) was matched to the insulin glargine cohort (n = 13,869) using Mahalanobis distance matching with propensity score calipers. Multivariable analyses of the matched cohorts of individuals with serum creatinine results (n = 1183 Dulaglutide and 1183 insulin glargine) examined the association between intent-to-treat therapy and changes in eGFR. In addition, multivariable analyses were also conducted on a subset of these patients who also had recorded HbA1c tests (n = 1088 Dulaglutide and 1088 insulin glargine) to examine the association between changes in HbA1c during the 1 year postperiod. Findings Among patients who initiated Dulaglutide therapy, only 0.9% of patients had an index eGFR Implications In clinical practice, the use of Dulaglutide was relatively more limited in patients with a higher degree of renal impairment compared with use of insulin glargine. However, initiation of Dulaglutide therapy, compared with insulin glargine therapy, was associated with a significantly smaller decrease in eGFR and a larger reduction in HbA1c during the 1 year postperiod.

  • effect of once weekly Dulaglutide by baseline beta cell function in people with type 2 diabetes in the award programme
    Diabetes Obesity and Metabolism, 2018
    Co-Authors: Chantal Mathieu, Fady T Botros, Chrisanthi A. Karanikas, Vivian T Thieu, Stefano Del Prato, Imre Pavo, N Jia, Axel Haupt, Luisemilio Garciaperez
    Abstract:

    Glucagon-like peptide-1 receptor agonists lower blood glucose in type 2 diabetes (T2D) partially through glucose-dependent stimulation of insulin secretion. The aim of this study was to investigate whether beta-cell function (as measured by HOMA2-%B) at baseline affects the glycaemic response to Dulaglutide. Dulaglutide-treated patients from AWARD-1, AWARD-3 and AWARD-6 clinical studies were categorised based on their homeostatic model assessment of beta-cell function (HOMA2-%B) tertiles. Changes in glycaemic measures in response to treatment with once-weekly Dulaglutide were evaluated in each HOMA2-%B tertile. Patients with low HOMA2-%B had higher baseline glycated haemoglobin (HbA1c), fasting and postprandial blood glucose, and longer duration of diabetes (P < .001, all) (mean low, middle and high tertiles with Dulaglutide 1.5 mg: HOMAB-2%B, 31%, 58%, 109%; HbA1c, 8.7%, 7.7%, 7.3%, respectively). At 26 weeks, the low tertile experienced larger reductions in HbA1c compared to the high tertile with Dulaglutide 1.5 mg (mean; -1.55% vs. -0.98% [-16.94 vs. -10.71 mmol/mol]). Differences between low and high tertiles disappeared when adjusted for baseline HbA1c (LSM; -1.00 vs. -1.18% [-10.93 vs. -12.90 mmol/mol]). Greater decreases in fasting blood glucose and greater increases in fasting C-peptide were observed in the low tertile. Similar increases in HOMA2-%B were observed in all tertiles. Dulaglutide demonstrated clinically relevant HbA1c reduction irrespective of estimated baseline beta-cell function.

  • Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial
    The lancet. Diabetes & endocrinology, 2018
    Co-Authors: Katherine R. Tuttle, Mark Lakshmanan, Brian Rayner, Robert S. Busch, Alan G. Zimmermann, D. Bradley Woodward, Fady T Botros
    Abstract:

    Summary Background Many antihyperglycaemic drugs, including insulin, are primarily cleared by the kidneys, restricting treatment options for patients with kidney disease. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys, and confers a lower risk of hypoglycaemia than does insulin. We assessed the efficacy and safety of Dulaglutide in patients with type 2 diabetes and moderate-to-severe chronic kidney disease. Methods AWARD-7 was a multicentre, open-label trial done at 99 sites in nine countries. Eligible patients were adults with type 2 diabetes and moderate-to-severe chronic kidney disease (stages 3–4), with an HbA 1c of 7·5–10·5%, and who were being treated with insulin or insulin plus an oral antihyperglycaemic drug and were taking a maximum tolerated dose of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Participants were randomly assigned (1:1:1) by use of a computer-generated random sequence with an interactive response system to once-weekly injectable Dulaglutide 1·5 mg, once-weekly Dulaglutide 0·75 mg, or daily insulin glargine as basal therapy, all in combination with insulin lispro, for 52 weeks. Insulin glargine and lispro doses were titrated as per an adjustment algorithm; Dulaglutide doses were masked to participants and investigators. The primary outcome was HbA 1c at 26 weeks, with a 0·4% non-inferiority margin. Secondary outcomes included estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). The primary analysis population was all randomly assigned patients who received at least one dose of study treatment and had at least one post-randomisation HbA 1c measurement. The safety population was all patients who received at least one dose of study treatment and had any post-dose data. This study is registered with ClinicalTrials.gov, number NCT01621178. Findings Between Aug 15, 2012, and Nov 30, 2015, 577 patients were randomly assigned, 193 to Dulaglutide 1·5 mg, 190 to Dulaglutide 0·75 mg, and 194 to insulin glargine. The effects on HbA 1c change at 26 weeks of Dulaglutide 1·5 mg and 0·75 mg were non-inferior to those of insulin glargine (least squares mean [LSM] −1·2% [SE 0·1] with Dulaglutide 1·5 mg [183 patients]; −1·1% [0·1] with Dulaglutide 0·75 mg [180 patients]; −1·1% [0·1] with insulin glargine [186 patients]; one-sided p≤0·0001 for both Dulaglutide doses vs insulin glargine). The differences in HbA 1c concentration at 26 weeks between Dulaglutide and insulin glargine treatments were LSM difference −0·05% (95% CI −0·26 to 0·15, p 1c -lowering effects persisted to 52 weeks (LSM −1·1% [SE 0·1] with Dulaglutide 1·5 mg; −1·1% [0·1] with Dulaglutide 0·75 mg; −1·0% [0·1] with insulin glargine). At 52 weeks, eGFR was higher with Dulaglutide 1·5 mg (Chronic Kidney Disease Epidemiology Collaboration equation by cystatin C geometric LSM 34·0 mL/min per 1·73 m 2 [SE 0·7]; p=0·005 vs insulin glargine) and Dulaglutide 0·75 mg (33·8 mL/min per 1·73 m 2 [0·7]; p=0·009 vs insulin glargine) than with insulin glargine (31·3 mL/min per 1·73 m 2 [0·7]). At 52 weeks, the effects of Dulaglutide 1·5 mg and 0·75 mg on UACR reduction were not significantly different from that of insulin glargine (LSM −22·5% [95% CI −35·1 to −7·5] with Dulaglutide 1·5 mg; −20·1% [–33·1 to −4·6] with Dulaglutide 0·75 mg; −13·0% [–27·1 to 3·9] with insulin glargine). Proportions of patients with any serious adverse events were similar across groups (20% [38 of 192] with Dulaglutide 1·5 mg, 24% [45 of 190] with Dulaglutide 0·75 mg, and 27% [52 of 194] with insulin glargine). Dulaglutide was associated with higher rates of nausea (20% [38 of 192] with Dulaglutide 1·5 mg and 14% [27 of 190] with 0·75 mg, vs 5% [nine of 194] with insulin glargine) and diarrhoea (17% [33 of 192] with Dulaglutide 1·5 mg and 16% [30 of 190] with 0·75 mg, vs 7% [14 of 194] with insulin glargine) and lower rates of symptomatic hypoglycaemia (4·4 events per patient per year with Dulaglutide 1·5 mg and 4·3 with Dulaglutide 0·75 mg, vs 9·6 with insulin glargine). End-stage renal disease occurred in 38 participants: eight (4%) of 192 with Dulaglutide 1·5 mg, 14 (7%) of 190 with Dulaglutide 0·75 mg, and 16 (8%) of 194 with insulin glargine. Interpretation In patients with type 2 diabetes and moderate-to-severe chronic kidney disease, once-weekly Dulaglutide produced glycaemic control similar to that achieved with insulin glargine, with reduced decline in eGFR. Dulaglutide seems to be safe to use to achieve glycaemic control in patients with moderate-to-severe chronic kidney disease. Funding Eli Lilly and Company.

  • effects of once weekly Dulaglutide on kidney function in patients with type 2 diabetes in phase ii and iii clinical trials
    Diabetes Obesity and Metabolism, 2017
    Co-Authors: Katherine R. Tuttle, Jaime A. Davidson, Greg Anglin, Kristine D. Harper, Dwight T Mckinney, Fady T Botros
    Abstract:

    Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes (T2D). Integrated data from 9 phase II and III trials in people with T2D (N = 6005) were used to evaluate the effects of Dulaglutide on estimated glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology Collaboration]), urine albumin-to-creatinine ratio (UACR) and kidney adverse events (AEs). No significant differences in eGFR were observed during treatment for Dulaglutide vs placebo, active comparators or insulin glargine (mean ± standard deviation values: Dulaglutide vs placebo: 87.8 ± 17.7 vs 88.2 ± 17.9 mL/min/1.73 m2 , P = .075; Dulaglutide vs active comparators: 89.9 ± 16.7 vs 88.8 ± 16.3 mL/min/1.73 m2 , P = .223; and Dulaglutide vs insulin glargine: 85.9 ± 18.2 vs 83.9 ± 18.6 mL/min/1.73 m2 , P = .423). Lower UACR values were observed for Dulaglutide vs placebo, active comparators and insulin glargine (at 26 weeks, median [Q1-Q3] values were: Dulaglutide vs placebo: 8.0 [4.4-20.4] vs 8.0 [4.4-23.9] mg/g, P = .023; Dulaglutide vs active comparators: 8.0 [4.4-21.2] vs 8.9 [4.4-27.4] mg/g, P = .013; and Dulaglutide vs insulin glargine: 8.9 [4.4-29.2] vs 12.4 [5.3-50.5] mg/g, P = .029). AEs reflecting potential acute renal failure were 3.4, 1.7 and 7.0 events/1000 patient-years for Dulaglutide, active comparators and placebo, respectively. In conclusion, Dulaglutide treatment of clinical trial participants with T2D did not affect eGFR and slightly decreased albuminuria.

  • Effects of once‐weekly Dulaglutide on kidney function in patients with type 2 diabetes in phase II and III clinical trials
    Diabetes obesity & metabolism, 2016
    Co-Authors: Katherine R. Tuttle, T. Dwight Mckinney, Jaime A. Davidson, Greg Anglin, Kristine D. Harper, Fady T Botros
    Abstract:

    Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes (T2D). Integrated data from 9 phase II and III trials in people with T2D (N = 6005) were used to evaluate the effects of Dulaglutide on estimated glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology Collaboration]), urine albumin-to-creatinine ratio (UACR) and kidney adverse events (AEs). No significant differences in eGFR were observed during treatment for Dulaglutide vs placebo, active comparators or insulin glargine (mean ± standard deviation values: Dulaglutide vs placebo: 87.8 ± 17.7 vs 88.2 ± 17.9 mL/min/1.73 m2 , P = .075; Dulaglutide vs active comparators: 89.9 ± 16.7 vs 88.8 ± 16.3 mL/min/1.73 m2 , P = .223; and Dulaglutide vs insulin glargine: 85.9 ± 18.2 vs 83.9 ± 18.6 mL/min/1.73 m2 , P = .423). Lower UACR values were observed for Dulaglutide vs placebo, active comparators and insulin glargine (at 26 weeks, median [Q1-Q3] values were: Dulaglutide vs placebo: 8.0 [4.4-20.4] vs 8.0 [4.4-23.9] mg/g, P = .023; Dulaglutide vs active comparators: 8.0 [4.4-21.2] vs 8.9 [4.4-27.4] mg/g, P = .013; and Dulaglutide vs insulin glargine: 8.9 [4.4-29.2] vs 12.4 [5.3-50.5] mg/g, P = .029). AEs reflecting potential acute renal failure were 3.4, 1.7 and 7.0 events/1000 patient-years for Dulaglutide, active comparators and placebo, respectively. In conclusion, Dulaglutide treatment of clinical trial participants with T2D did not affect eGFR and slightly decreased albuminuria.

Kristina S. Boye - One of the best experts on this subject based on the ideXlab platform.

  • Dulaglutide Shows Sustained Reduction in Glycosylated Hemoglobin Values: 2-Year US Real-world Study Results
    Clinical therapeutics, 2020
    Co-Authors: Reema Mody, Kristina S. Boye, Michael Grabner, Chia-chen Teng, Anita Y. M. Kwan
    Abstract:

    Abstract Purpose Due to the chronic and progressive nature of type 2 diabetes mellitus (T2DM), it is important to understand the long-term outcomes associated with antihyperglycemic medications. There are currently few long-term studies evaluating the real-world effectiveness of Dulaglutide, a glucagon-like peptide-1 receptor agonist. The primary objective of this retrospective observational study was to evaluate glycemic control over a 24-month follow-up period among Dulaglutide initiators with continuous treatment. The study used US claims data from the HealthCore Integrated Research Database between May 2014 and May 2019. Methods Patients were included if they were ≥18 years old with T2DM and had ≥1 pharmacy claim for Dulaglutide during the index period between November 2014 and May 2017 (with index date = set as the earliest Dulaglutide fill during index period), continuous enrollment in the 6 months' preindex and 24 months' postindex, ≥1 claim for Dulaglutide or ≥60 days’ supply in every quarter during the 24-month follow-up period, and ≥1 glycosylated hemoglobin (HbA1c) result at both baseline and 24 months. Findings At baseline, 872 patients (47.5% female) had a mean (SD) age of 54.5 (8.2) years and an HbA1c value of 8.68% (1.8%) (71.36 [19.7] mmol/mol). More than two thirds were being treated for dyslipidemia, hypertension, or cardiovascular disease. A significant HbA1c reduction was observed from baseline to 24 months (−1.3% [–14.2 mmol/mol]; P  Implications In this real-world study among Dulaglutide initiators with continuous treatment, a clinically significant reduction in HbA1c value was seen at the 3-month assessment and persisted for up to 24 months. These data support the use of Dulaglutide as an effective long-term treatment for T2DM in clinical practice.

  • Real-World Effectiveness of Dulaglutide in Patients with Type 2 Diabetes Mellitus: A Literature Review
    Diabetes Therapy, 2020
    Co-Authors: Susan Robinson, Kristina S. Boye, Reema Mody, Alena Antonie Strizek, Manige Konig, Raleigh E. Malik, Tessa Kennedy-martin
    Abstract:

    Introduction Randomized 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. Methods The 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. Results A 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  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). Conclusion Evidence 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.

  • Real-World Effectiveness of Dulaglutide in Patients with Type 2 Diabetes Mellitus: A Literature Review.
    Diabetes therapy : research treatment and education of diabetes and related disorders, 2020
    Co-Authors: Susan Robinson, Kristina S. Boye, Reema Mody, Alena Antonie Strizek, Manige Konig, Raleigh E. Malik, Tessa Kennedy-martin
    Abstract:

    Randomized 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. The 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. A 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   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). Evidence 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.

  • assessing patient preference between the Dulaglutide pen and the semaglutide pen a crossover study prefer
    Diabetes Obesity and Metabolism, 2020
    Co-Authors: Louis S Matza, Kristina S. Boye, Katie D Stewart, Karin S Coyne, Paula K Wullenweber, Katelyn Cutts, Jessica B Jordan, Qianqian Wang, Brooke M Currie, Karen G Malley
    Abstract:

    AIM When selecting treatments for type 2 diabetes (T2D), it is important to consider not only efficacy and safety, but also other treatment attributes that have an impact on patient preference. The objective of this study was to examine preference between injection devices used for two weekly GLP-1 receptor agonists. MATERIALS AND METHODS The PREFER study was an open-label, multicentre, randomized, crossover study assessing patient preference for Dulaglutide and semaglutide injection devices among injection-naive patients receiving oral medication for type 2 diabetes. After being trained to use each device, participants performed all steps of injection preparation and administered mock injections into an injection pad. Time-to-train (TTT) for each device was assessed in a subset. RESULTS There were 310 evaluable participants (48.4% female; mean age, 60.0 years; 78 participants in the TTT subgroup). More participants preferred the Dulaglutide device than the semaglutide device (84.2% vs. 12.3%; P < 0.0001). More participants perceived the Dulaglutide device to have greater ease of use (86.8% vs. 6.8%; P < 0.0001). After preparing and using the devices, more participants were willing to use the Dulaglutide device (93.5%) than the semaglutide device (45.8%). Training participants to use the Dulaglutide device required less time than the semaglutide device (3.38 vs. 8.14 minutes; P < 0.0001). CONCLUSIONS Participants with type 2 diabetes preferred the Dulaglutide injection device to the semaglutide injection device. If patients prefer a device, they may be more willing to use the medication, which could result in better health outcomes. Furthermore, a shorter training time for injection devices may be helpful in busy clinical practice settings.

  • Effects of Dulaglutide and Insulin Glargine on Estimated Glomerular Filtration Rate in a Real-world Setting
    Clinical therapeutics, 2018
    Co-Authors: Kristina S. Boye, Fady T Botros, Reema Mody, Maureen J. Lage, Brad Woodward
    Abstract:

    Abstract Purpose The aims of this study were to use real-world treatment results to compare changes in estimated glomerular filtration rate (eGFR) and glycosylated hemoglobin (HbA1c) among patients with type 2 diabetes who initiated treatment with Dulaglutide or insulin glargine and to determine the proportions of patients with renal impairment who initiate each treatment. Methods The study used data from the Practice Fusion electronic health records database from October 2013 through June 2017. Adults with type 2 diabetes who initiated Dulaglutide or insulin glargine therapy and had multiple recorded serum creatinine and/or HbA1c laboratory test results were included in the study. The Dulaglutide cohort (n = 1222) was matched to the insulin glargine cohort (n = 13,869) using Mahalanobis distance matching with propensity score calipers. Multivariable analyses of the matched cohorts of individuals with serum creatinine results (n = 1183 Dulaglutide and 1183 insulin glargine) examined the association between intent-to-treat therapy and changes in eGFR. In addition, multivariable analyses were also conducted on a subset of these patients who also had recorded HbA1c tests (n = 1088 Dulaglutide and 1088 insulin glargine) to examine the association between changes in HbA1c during the 1 year postperiod. Findings Among patients who initiated Dulaglutide therapy, only 0.9% of patients had an index eGFR Implications In clinical practice, the use of Dulaglutide was relatively more limited in patients with a higher degree of renal impairment compared with use of insulin glargine. However, initiation of Dulaglutide therapy, compared with insulin glargine therapy, was associated with a significantly smaller decrease in eGFR and a larger reduction in HbA1c during the 1 year postperiod.

Reema Mody - One of the best experts on this subject based on the ideXlab platform.

  • Dulaglutide Shows Sustained Reduction in Glycosylated Hemoglobin Values: 2-Year US Real-world Study Results
    Clinical therapeutics, 2020
    Co-Authors: Reema Mody, Kristina S. Boye, Michael Grabner, Chia-chen Teng, Anita Y. M. Kwan
    Abstract:

    Abstract Purpose Due to the chronic and progressive nature of type 2 diabetes mellitus (T2DM), it is important to understand the long-term outcomes associated with antihyperglycemic medications. There are currently few long-term studies evaluating the real-world effectiveness of Dulaglutide, a glucagon-like peptide-1 receptor agonist. The primary objective of this retrospective observational study was to evaluate glycemic control over a 24-month follow-up period among Dulaglutide initiators with continuous treatment. The study used US claims data from the HealthCore Integrated Research Database between May 2014 and May 2019. Methods Patients were included if they were ≥18 years old with T2DM and had ≥1 pharmacy claim for Dulaglutide during the index period between November 2014 and May 2017 (with index date = set as the earliest Dulaglutide fill during index period), continuous enrollment in the 6 months' preindex and 24 months' postindex, ≥1 claim for Dulaglutide or ≥60 days’ supply in every quarter during the 24-month follow-up period, and ≥1 glycosylated hemoglobin (HbA1c) result at both baseline and 24 months. Findings At baseline, 872 patients (47.5% female) had a mean (SD) age of 54.5 (8.2) years and an HbA1c value of 8.68% (1.8%) (71.36 [19.7] mmol/mol). More than two thirds were being treated for dyslipidemia, hypertension, or cardiovascular disease. A significant HbA1c reduction was observed from baseline to 24 months (−1.3% [–14.2 mmol/mol]; P  Implications In this real-world study among Dulaglutide initiators with continuous treatment, a clinically significant reduction in HbA1c value was seen at the 3-month assessment and persisted for up to 24 months. These data support the use of Dulaglutide as an effective long-term treatment for T2DM in clinical practice.

  • Real-World Effectiveness of Dulaglutide in Patients with Type 2 Diabetes Mellitus: A Literature Review
    Diabetes Therapy, 2020
    Co-Authors: Susan Robinson, Kristina S. Boye, Reema Mody, Alena Antonie Strizek, Manige Konig, Raleigh E. Malik, Tessa Kennedy-martin
    Abstract:

    Introduction Randomized 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. Methods The 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. Results A 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  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). Conclusion Evidence 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.

  • Real-World Effectiveness of Dulaglutide in Patients with Type 2 Diabetes Mellitus: A Literature Review.
    Diabetes therapy : research treatment and education of diabetes and related disorders, 2020
    Co-Authors: Susan Robinson, Kristina S. Boye, Reema Mody, Alena Antonie Strizek, Manige Konig, Raleigh E. Malik, Tessa Kennedy-martin
    Abstract:

    Randomized 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. The 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. A 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   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). Evidence 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.

  • 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
    Diabetes Obesity and Metabolism, 2019
    Co-Authors: Reema Mody, Qing Huang, Ruizhi Zhao, Hiren Patel, Michael Grabner, Laura Fernandez Lando
    Abstract:

    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.

  • Effects of Dulaglutide and Insulin Glargine on Estimated Glomerular Filtration Rate in a Real-world Setting
    Clinical therapeutics, 2018
    Co-Authors: Kristina S. Boye, Fady T Botros, Reema Mody, Maureen J. Lage, Brad Woodward
    Abstract:

    Abstract Purpose The aims of this study were to use real-world treatment results to compare changes in estimated glomerular filtration rate (eGFR) and glycosylated hemoglobin (HbA1c) among patients with type 2 diabetes who initiated treatment with Dulaglutide or insulin glargine and to determine the proportions of patients with renal impairment who initiate each treatment. Methods The study used data from the Practice Fusion electronic health records database from October 2013 through June 2017. Adults with type 2 diabetes who initiated Dulaglutide or insulin glargine therapy and had multiple recorded serum creatinine and/or HbA1c laboratory test results were included in the study. The Dulaglutide cohort (n = 1222) was matched to the insulin glargine cohort (n = 13,869) using Mahalanobis distance matching with propensity score calipers. Multivariable analyses of the matched cohorts of individuals with serum creatinine results (n = 1183 Dulaglutide and 1183 insulin glargine) examined the association between intent-to-treat therapy and changes in eGFR. In addition, multivariable analyses were also conducted on a subset of these patients who also had recorded HbA1c tests (n = 1088 Dulaglutide and 1088 insulin glargine) to examine the association between changes in HbA1c during the 1 year postperiod. Findings Among patients who initiated Dulaglutide therapy, only 0.9% of patients had an index eGFR Implications In clinical practice, the use of Dulaglutide was relatively more limited in patients with a higher degree of renal impairment compared with use of insulin glargine. However, initiation of Dulaglutide therapy, compared with insulin glargine therapy, was associated with a significantly smaller decrease in eGFR and a larger reduction in HbA1c during the 1 year postperiod.

Zachary Skrivanek - One of the best experts on this subject based on the ideXlab platform.

  • Low incidence of anti-drug antibodies in patients with type 2 diabetes treated with once-weekly glucagon-like peptide-1 receptor agonist Dulaglutide.
    Diabetes obesity & metabolism, 2016
    Co-Authors: Zvonko Milicevic, Greg Anglin, Kristine D. Harper, Zachary Skrivanek, Robert J. Konrad, Wolfgang Glaesner, Chrisanthi A. Karanikas, Kenneth Mace
    Abstract:

    Therapeutic administration of peptides may result in anti-drug antibody (ADA) formation, hypersensitivity adverse events (AEs) and reduced efficacy. As a large peptide, the immunogenicity of once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist Dulaglutide is of considerable interest. The present study assessed the incidence of treatment-emergent Dulaglutide ADAs, hypersensitivity AEs, injection site reactions (ISRs), and glycaemic control in ADA-positive patients in nine phase II and phase III trials (Dulaglutide, N = 4006; exenatide, N = 276; non-GLP-1 comparators, N = 1141). Treatment-emergent Dulaglutide ADAs were detected using a solid-phase extraction acid dissociation binding assay. Neutralizing ADAs were detected using a cell-based assay derived from human endothelial kidney cells (HEK293). A total of 64 Dulaglutide-treated patients (1.6% of the population) tested ADA-positive versus eight (0.7%) from the non-GLP-1 comparator group. Of these 64 patients, 34 (0.9%) had Dulaglutide-neutralizing ADAs, 36 (0.9%) had native-sequence GLP-1 (nsGLP-1) cross-reactive ADAs and four (0.1%) had nsGLP-1 neutralization ADAs. The incidence of hypersensitivity AEs and ISRs was similar in the Dulaglutide versus placebo groups. No Dulaglutide ADA-positive patient reported hypersensitivity AEs. Because of the low incidence of ADAs, it was not possible to establish their effect on glycaemic control.

  • achieving the composite endpoint of glycated haemoglobin 7 0 no weight gain and no hypoglycaemia in the once weekly Dulaglutide award programme
    Diabetes Obesity and Metabolism, 2016
    Co-Authors: Kathleen M Dungan, Zachary Skrivanek, Itamar Raz, Whitney Sealls, Jessie L Fahrbach
    Abstract:

    Aim To compare the effectiveness of Dulaglutide 1.5 and 0.75 mg with active comparators and placebo with regard to a composite endpoint of glycated haemoglobin (HbA1c), weight and hypoglycaemia, using post hoc analyses. Methods A logistic regression analysis was performed on the intention-to-treat population, using data from the last observation carried forward, and the composite endpoint of HbA1c <7.0% (53 mmol/mol), no weight gain (≤0 kg) and no hypoglycaemia (glucose <3.0 mmol/l or severe hypoglycaemia) after 26 weeks for each trial in the AWARD programme separately. Results At 26 weeks, within each study, 37–58% of patients on Dulaglutide 1.5 mg, 27–49% of patients on Dulaglutide 0.75 mg, and 9–61% of patients on active comparators achieved the composite endpoint. Significantly more patients reached the composite endpoint with Dulaglutide 1.5 mg than with metformin, sitagliptin, exenatide twice daily or insulin glargine: odds ratio (OR) 1.5 [95% confidence interval (CI) 1.0, 2.2; p < 0.05], OR 4.5 (95% CI 3.0, 6.6; p < 0.001), OR 2.6 (95% CI 1.8, 3.7; p < 0.001) and OR 7.4 (95% CI 4.4, 12.6; p < 0.001), respectively, with no difference between Dulaglutide 1.5 mg and liraglutide 1.8 mg. In addition, significantly more patients reached the composite endpoint with Dulaglutide 0.75 mg than with sitagliptin or insulin glargine: OR 3.3 (95% CI 2.2, 4.8; p < 0.001) and OR 4.5 (95% CI 2.7, 7.8; p < 0.001), respectively. Conclusions Dulaglutide is an effective treatment option, resulting in a similar or greater proportion of patients reaching the HbA1c target of <7.0% (53 mmol/mol), without weight gain or hypoglycaemia compared with active comparators.

  • safety and efficacy of once weekly Dulaglutide versus sitagliptin after 2 years in metformin treated patients with type 2 diabetes award 5 a randomized phase iii study
    Diabetes Obesity and Metabolism, 2015
    Co-Authors: Ruth S. Weinstock, Michael A. Nauck, Guillermo E. Umpierrez, Bruno Guerci, Zachary Skrivanek, Zvonko Milicevic
    Abstract:

    Aims To compare the once-weekly glucagon-like peptide-1 (GLP-1) receptor Dulaglutide with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin after 104 weeks of treatment. Methods This AWARD-5 study was a multicentre, double-blind trial that randomized participants to Dulaglutide (1.5 or 0.75 mg) or sitagliptin 100 mg for 104 weeks or placebo (reported separately) for 26 weeks. Change in glycated haemoglobin (HbA1c) concentration from baseline was the primary efficacy measure. A total of 1098 participants with HbA1c concentrations ≥7.0% (≥53.0 mmol/mol) and ≤9.5% (≤80.3 mmol/mol) were randomized, and 657 (59.8%) completed the study. We report results for Dulaglutide and sitagliptin at the final endpoint. Results Changes in HbA1c at 104 weeks were (least squares mean ± standard error) −0.99 ± 0.06% (−10.82 ± 0.66 mmol/mol), −0.71 ± 0.07% (−7.76 ± 0.77 mmol/mol) and −0.32 ± 0.06% (−3.50 ± 0.66 mmol/mol) for Dulaglutide 1.5 mg, Dulaglutide 0.75 mg and sitagliptin, respectively (p < 0.001, both Dulaglutide doses vs sitagliptin). Weight loss was greater with Dulaglutide 1.5 mg (p < 0.001) and similar with 0.75 mg versus sitagliptin (2.88 ± 0.25, 2.39 ± 0.26 and 1.75 ± 0.25 kg, respectively). Gastrointestinal adverse events were more common with Dulaglutide 1.5 and 0.75 mg versus sitagliptin (nausea 17 and 15% vs 7%, diarrhoea 16 and 12% vs 6%, vomiting 14 and 8% vs 4% respectively). Pancreatic, thyroid, cardiovascular and hypersensitivity safety were similar across groups. Conclusions Dulaglutide doses provided superior glycaemic control and Dulaglutide 1.5 mg resulted in greater weight reduction versus sitagliptin at 104 weeks, with acceptable safety.

  • Safety and efficacy of once‐weekly Dulaglutide versus sitagliptin after 2 years in metformin‐treated patients with type 2 diabetes (AWARD‐5): a randomized, phase III study
    Diabetes obesity & metabolism, 2015
    Co-Authors: Ruth S. Weinstock, Michael A. Nauck, Guillermo E. Umpierrez, Bruno Guerci, Zachary Skrivanek, Zvonko Milicevic
    Abstract:

    Aims To compare the once-weekly glucagon-like peptide-1 (GLP-1) receptor Dulaglutide with the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin after 104 weeks of treatment. Methods This AWARD-5 study was a multicentre, double-blind trial that randomized participants to Dulaglutide (1.5 or 0.75 mg) or sitagliptin 100 mg for 104 weeks or placebo (reported separately) for 26 weeks. Change in glycated haemoglobin (HbA1c) concentration from baseline was the primary efficacy measure. A total of 1098 participants with HbA1c concentrations ≥7.0% (≥53.0 mmol/mol) and ≤9.5% (≤80.3 mmol/mol) were randomized, and 657 (59.8%) completed the study. We report results for Dulaglutide and sitagliptin at the final endpoint. Results Changes in HbA1c at 104 weeks were (least squares mean ± standard error) −0.99 ± 0.06% (−10.82 ± 0.66 mmol/mol), −0.71 ± 0.07% (−7.76 ± 0.77 mmol/mol) and −0.32 ± 0.06% (−3.50 ± 0.66 mmol/mol) for Dulaglutide 1.5 mg, Dulaglutide 0.75 mg and sitagliptin, respectively (p 

  • Dose-finding results in an adaptive, seamless, randomized trial of once-weekly Dulaglutide combined with metformin in type 2 diabetes patients (AWARD-5)
    Diabetes obesity & metabolism, 2014
    Co-Authors: Zachary Skrivanek, Zvonko Milicevic, Brenda Gaydos, Jenny Y. Chien, Mary Jane Geiger, Michael Heathman, Scott M Berry, James H. Anderson, T. Forst, Donald Berry
    Abstract:

    Aims AWARD-5 was an adaptive, seamless, double-blind study comparing Dulaglutide, a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist, with placebo at 26 weeks and sitagliptin up to 104 weeks. The study also included a dose-finding portion whose results are presented here. Methods Type 2 diabetes (T2D) patients on metformin were randomized 3 : 1 : 1 to seven Dulaglutide doses, sitagliptin (100 mg), or placebo. A Bayesian algorithm was used for randomization and dose selection. Patients were adaptively randomized to Dulaglutide doses using available data on the basis of a clinical utility index (CUI) of glycosylated haemoglobin A1c (HbA1c) versus sitagliptin at 52 weeks and weight, pulse rate (PR) and diastolic blood pressure (DBP) versus placebo at 26 weeks. The algorithm randomly assigned patients until two doses were selected. Results Dulaglutide 1.5 mg was determined to be the optimal dose. Dulaglutide 0.75 mg met criteria for the second dose. Dulaglutide 1.5 mg showed the greatest Bayesian mean change from baseline (95% credible interval) in HbA1c versus sitagliptin at 52 weeks −0.63 (−0.98 to −0.20)%. Dulaglutide 2.0 mg showed the greatest placebo-adjusted mean change in weight [−1.99 (−2.88 to −1.20) kg] and in PR [0.78 (-2.10 to 3.80) bpm]. Dulaglutide 1.5 mg showed the greatest placebo-adjusted mean change in DBP [−0.62 (−3.40 to 2.30) mmHg]. Conclusions The Bayesian algorithm allowed for an efficient exploration of a large number of doses and selected Dulaglutide doses of 1.5 and 0.75 mg for further investigation in this trial.

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