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Background and Aims Anaemia is a common complication in patients with chronic kidney disease (CKD) and is associated with increased mortality, cardiovascular complications, reduced quality of life and increased use of healthcare resources. Mathematical modelling based on robust epidemiological and clinical data is a useful approach for predicting the future burden of disease and the impact of different intervention scenarios; this is important for health service planning. This analysis uses a microsimulation model, Inside ANEMIA of CKD, to predict the effects of a hypothetical intervention scenario that reduces the prevalence of anaemia of CKD on related healthcare costs in the USA from 2020 to 2025. Method A virtual cohort representing the US population was created within the Inside ANEMIA of CKD microsimulation model framework using demographics and epidemiological data drawn from the US Census Bureau, the Centers for Disease Control and Prevention, and the National Health and Nutrition Examination Survey. In the cohort, virtual individuals were ascribed an age–sex-stratified CKD status (defined by estimated glomerular filtration rate and albuminuria levels, as per international guidelines) and anaemia status (defined by haemoglobin level as mild, moderate or severe, as per WHO criteria) based on US prevalence data. Key comorbidities (type 2 diabetes, heart failure and hypertension) were also assigned, reflecting US-specific population statistics. Healthcare costs related to CKD and anaemia of CKD were taken from the published literature. The study modelled the effects on healthcare costs of a hypothetical intervention scenario in which the prevalence of moderate and severe anaemia is reduced by 20% per year from 2020 to 2025 compared with no intervention (baseline). In each scenario (i.e. intervention or baseline), the modelling analysis estimated healthcare costs related to CKD and anaemia (including inpatient, outpatient, pharmacy costs) for patients with moderate or severe anaemia of CKD. The model did not adjust for the potential costs of the intervention. Results Preliminary results predict that, with the hypothetical intervention, there could be 1.40 million fewer patients with moderate or severe anaemia of CKD in the USA in 2025 compared with no intervention (1.45 million versus 2.85 million). This represents a 49% reduction in cases of moderate or severe anaemia of CKD in 2025 with the intervention versus no intervention. The intervention is projected to lead to a reduction of approximately US$18 billion in annual direct healthcare costs in 2025 for patients with moderate or severe anaemia of CKD compared with no intervention (US$26 billion versus US$44 billion). Conclusion The Inside ANEMIA of CKD microsimulation model predicts that a hypothetical intervention which reduces the prevalence of moderate and severe anaemia of CKD would reduce direct healthcare costs. This suggests that interventions effective at reducing the prevalence of anaemia of CKD would help to reduce the economic burden on healthcare services.

Background and Aims Chronic kidney disease (CKD) is a costly public health issue, which affects 13.4% of the population globally. Anaemia is a common complication in patients with CKD resulting in reduced health-related quality of life and high healthcare costs. The objective of this analysis was to estimate the direct medical care cost offsets of the investigational agent roxadustat for the treatment of anaemia in patients with dialysis-dependent (DD) CKD from a Canadian healthcare perspective. Method Data from the roxadustat global phase 3 program were used to estimate the incidence of rescue therapy or iron supplementation use (i.e. intravenous iron, erythropoiesis-stimulating agents [ESAs] or red blood cell transfusions) and major adverse cardiovascular events (MACE+) for roxadustat compared with ESAs in DD patients with anaemia of CKD. MACE+ included myocardial infarction, stroke, unstable angina requiring hospitalization, congestive heart failure (CHF) requiring hospitalization, cardiovascular death and other death. Published Canadian cost data were used to estimate event costs. Drug acquisition costs for roxadustat and ESAs were not considered. A hypothetical cohort of 10,000 Canadian adult DD patients (90% undergoing haemodialysis, 10% undergoing peritoneal dialysis) with treatable anaemia was modelled to determine net medical care cost offsets annually and cumulatively compared with ESAs over a 4-year time horizon. Results Preliminary results for patients with DD CKD show that, compared with ESAs, roxadustat could produce sizeable net medical care cost offsets resulting from reductions in rescue therapy or iron supplementation use, specifically red blood cell transfusions, and from reductions in MACE+, specifically CHF hospitalizations. For the entire cohort of patients with DD CKD, cumulative medical care cost offsets for roxadustat were an estimated $162,609 for rescue therapy or iron supplementation use and $1,027,070 for MACE+ compared with ESAs. Conclusion This analysis provides evidence that treatment with roxadustat in DD patients with anaemia of CKD could result in considerable medical care cost offsets for roxadustat compared with ESAs.

Background and Aims Anaemia is common in patients with chronic kidney disease (CKD) and is associated with increased mortality, cardiovascular complications, reduced quality of life and increased use of healthcare resources. Based on robust epidemiological and clinical data, mathematical modelling is a useful approach for predicting the future burden of disease and the effects of different intervention scenarios, which is essential for health service planning. This analysis uses a microsimulation model, Inside ANEMIA of CKD, to project the impact of a hypothetical intervention scenario that reduces the prevalence of anaemia of CKD on related healthcare costs in Canada from 2020 to 2025. Method A virtual cohort representing the Canadian population was created within the Inside ANEMIA of CKD microsimulation model framework using national demographics and epidemiological data drawn from Statistics Canada and a provincial renal database. In the cohort, virtual individuals were ascribed an age- and sex-stratified CKD status (defined by estimated glomerular filtration rate and albuminuria levels, as per international guidelines) and anaemia status (defined as mild, moderate or severe based on haemoglobin level, as per WHO criteria) based on Canadian prevalence data. Key comorbidities (type 2 diabetes, heart failure and hypertension) were also assigned, reflecting Canada-specific population statistics. Costs related to the treatment of CKD were taken from the published literature, and are shown in Canadian dollars (C$). This modelling analysis evaluated the effects on healthcare costs of a hypothetical intervention scenario in which the prevalence of moderate and severe anaemia is reduced by 20% per year from 2020 to 2025 compared with no intervention (baseline). In each scenario (i.e. intervention or baseline), the modelling analysis estimated CKD-related healthcare costs for patients with moderate or severe anaemia of CKD. The modelling analysis did not adjust for the potential costs of the intervention. Results Preliminary results predict that, with the hypothetical intervention, there could be approximately 435,000 fewer patients with moderate or severe anaemia of CKD in Canada in 2025 compared with no intervention (approximately 497,000 versus 932,000). The intervention is projected to lead to a reduction of C$4.4 billion in annual direct healthcare costs in 2025 for patients with moderate or severe anaemia of CKD compared with no intervention (C$9.1 billion versus C$13.5 billion), assuming that all eligible patients are diagnosed and treated. Conclusion The Inside ANEMIA of CKD microsimulation model predicts that a hypothetical intervention which reduces the prevalence of moderate and severe anaemia of CKD would produce reductions in direct healthcare costs. This suggests that interventions effective at reducing the prevalence of anaemia of CKD would help to reduce the economic burden on healthcare services.

Background and Aims Anaemia is a common complication in patients with chronic kidney disease (CKD). Prevalence of anaemia increases with CKD severity and ranges from 17% in patients with stage 3 disease to over 50% in patients with stage 5 CKD who are not on dialysis. Anaemia of CKD is associated with increased mortality, cardiovascular complications, reduced quality of life and increased use of healthcare resources. Mathematical modelling based on robust epidemiological and clinical data is a useful approach for predicting the future burden of disease, which is important for health service planning. This analysis uses a microsimulation model, Inside ANEMIA of CKD, to project the economic burden of anaemia of CKD in Canada from 2020 to 2025. Method A virtual cohort representing the Canadian population was created within the Inside ANEMIA of CKD microsimulation model framework, using Canadian demographics and epidemiological data drawn from Statistics Canada and a provincial renal database. In the cohort, virtual individuals were ascribed an age–sex-stratified CKD status (defined by estimated glomerular filtration rate and albuminuria levels, as per international guidelines) and anaemia status (defined as mild, moderate or severe based on haemoglobin level, as per WHO criteria) based on Canadian prevalence data. Key comorbidities (type 2 diabetes, heart failure and hypertension) were also assigned, reflecting Canada-specific population statistics. Incidence rates for acute kidney injury and cardiovascular complications (heart failure, myocardial infarction and stroke) were drawn from the literature. Costs related to CKD, anaemia of CKD and associated complications were taken from Canadian government sources and the literature, and are shown in Canadian dollars (C$). Results Preliminary results show that, in Canada, the number of individuals with anaemia of CKD is projected to increase by approximately 0.8 million between 2020 and 2025 (from 1.8 million to 2.6 million). Annual healthcare costs for patients with anaemia of CKD are projected to increase by 17% by 2025 (from C$19.3 billion to C$22.5 billion). Between 2020 and 2025, the costs associated with cardiovascular complications in patients with anaemia of CKD are projected to increase by 28% for heart failure (from C$1.13 billion to C$1.45 billion), 26% for myocardial infarction (from C$0.83 billion to C$1.05 billion) and 29% for stroke (from C$0.99 billion to C$1.29 billion). Conclusion Inside ANEMIA of CKD is the first microsimulation model to project the economic burden of anaemia of CKD in Canada. Based on the modelling projections, the increase in the number of individuals with anaemia of CKD over the next 5 years will be accompanied by a parallel increase in associated healthcare costs and a marked rise in the cost of cardiovascular complications. Evidence-based therapies for anaemia of CKD that lower cardiovascular complications are needed to reduce the economic burden on healthcare services.

Background and Aims Anaemia is a common complication of chronic kidney disease (CKD) and is associated with reduced quality of life, cardiovascular complications, early mortality and a high economic burden for patients. Current treatment options for anaemia of CKD include subcutaneous (SC) or intravenous (IV) erythropoiesis-stimulating agents (ESAs) with or without supplementary iron and blood transfusions. New oral therapies for anaemia, such as hypoxia-inducible factor prolyl hydroxylase inhibitors, are in development and may have advantages for patients compared with ESAs. It is therefore crucial to understand the treatment attributes that patients consider most important. This study aimed to investigate patient preferences for potential anaemia of CKD treatments in adults with dialysis-dependent (DD) CKD in Australia and Canada. Method Adult patients with DD CKD completed a discrete choice experiment (DCE) online survey. In each scenario, patients were asked to choose between three hypothetical treatment alternatives (‘oral pill’, ‘subcutaneous injection’ and ‘intravenous injection’) with differing levels of attributes and an opt-out option (none of these treatments/current treatment) to treat anaemia of CKD. Treatment attributes focused on administration (where, how often and by whom), purchasing (where it is collected and the cost per month), additional benefits (e.g. whether it reduces ‘bad’/LDL cholesterol), side effects (chance of hospitalization from a heart attack or stroke due to the medicine) and the need for rescue therapy (IV iron or blood transfusion). The attributes and their levels were derived from existing market research, the literature and expert opinion. A mixed multinomial logit model, which allows for preference heterogeneity, was used to quantify the overall value of such treatments and the relative importance of each of the defining attributes. Australian patients were divided into those who were eligible for reduced prescription charges under the Pharmaceutical Benefits Scheme, such as the elderly or those on low incomes (referred to as concessions), and those who were not (general patients). Prescription charge concessions did not apply for Canadian patients. Results This preliminary analysis included 61 patients with DD CKD from Australia (n = 22) and Canada (n = 39). The majority of patients were receiving haemodialysis (Australia, 72.7%; Canada, 61.5%), and more than half received their dialysis in a clinic or hospital (Australia, 54.5%; Canada, 76.9%); 50% of the Australian patients were concessions. In both countries, patients were likely to choose a new treatment alternative over the opt-out, with the greatest preference for oral treatment among Australian general and Canadian patients, all else being equal. For Australian concession patients, cost per month was the most important attribute across all treatment options; the risk of side effects (i.e. hospitalization from a heart attack or stroke) was the second most important attribute, with patients preferring treatments with the lowest possible risk. For Australian general and Canadian patients, the risk of side effects and the cost per month were the two most important attributes, and had similar levels of importance. Patients in both countries were also concerned about the risk of needing rescue therapy, and valued reductions in the amount of ‘bad’/LDL cholesterol. Conclusion Results from this DCE study showed that the risk of side effects and the costs of treatment are the most important attributes for hypothetical anaemia of CKD treatment for patients with DD CKD. Australian general and Canadian patients showed a preference for oral therapy over SC or IV injection, all other factors being equal. These findings may help to guide clinicians when selecting treatments for anaemia of CKD for their patients, and may provide useful information when assessing the value of new or future treatments.

Chuan-Ming Hao,1 Eric T Wittbrodt,2 Eirini Palaka,3 Nicolas Guzman,4 Alicia Dunn,5 Susan Grandy6 1Fudan University, Huashan Hospital, Shanghai, People’s Republic of China; 2Biopharmaceuticals Medical Unit, AstraZeneca, Gaithersburg, MD, USA; 3Biopharmaceuticals Global Market Access, AstraZeneca, Cambridge, UK; 4Global Medicines Development, AstraZeneca, Gaithersburg, MD, USA; 5AstraZeneca Global Corporate Affairs Gaithersburg, Gaithersburg, MD, USA; 6Biopharmaceuticals Global Market Access, AstraZeneca, Gaithersburg, MD, USACorrespondence: Chuan-Ming HaoFudan University, Huashan Hospital, Shanghai, People’s Republic of ChinaTel +86-21-62480303Email chuanminghao@fudan.edu.cnBackground: Anemia is a common complication of chronic kidney disease (CKD) that may reduce patients’ health-related quality of life (HRQoL). This study explored the experience and knowledge of patients with CKD, with and without anemia, in China.Methods: A quantitative online survey was administered to 500 consenting Chinese patient volunteers aged ≥ 18 years with self-reported CKD, with or without anemia, between August 29, and September 17, 2018. Patients with cancer were excluded. The 27-question survey explored knowledge of anemia, HRQoL, anemia management, and interactions with healthcare providers.Results: Of 456 evaluable patients, 148 (32.5%) reported having anemia and 262 (57.5%) did not. Knowledge of anemia and its symptoms varied, and approximately half of all patients did not know their hemoglobin level. Patients with anemia expressed an adverse impact of anemia on HRQoL, most commonly lack of energy (65.5%), sadness/depression (54.1%), and feeling ill (50.0%). The most frequently reported treatments among these patients were dietary advice (68.9%), iron supplements (63.5%), and oral medications (53.4%). Although 89.2% of patients with anemia trusted their healthcare providers above other information sources, only 29.0% reported seeking information from them; this was despite 92.6% reporting wanting further information and support about managing conditions like anemia.Conclusion: Our findings suggest that patients with CKD, both with and without anemia, would benefit from increased awareness of anemia and more in-depth discussions with healthcare providers in order to facilitate better management of CKD and optimization of treatment plans.Keywords: anemia, chronic kidney disease, survey, patient perspectives, China

Background Anaemia, a common complication of chronic kidney disease (CKD), is associated with reduced health-related quality of life and physical functioning. This study investigated the knowledge, perceptions and awareness of anaemia in patients with CKD in the United States. Methods Between 29 August and 17 September 2018, an online survey was administered to consenting patients in the United States aged ≥ 18 years with self-reported CKD, with or without anaemia; patients with cancer were excluded. The survey comprised 27 questions, exploring anaemia knowledge, health-related quality of life, anaemia management, practitioner–patient relationships, and the information sources patients used. Results Of 446 patients with CKD, 255 (57.2%) were diagnosed with anaemia and 191 (42.8%) reported not being diagnosed with anaemia, or were unsure/could not remember (non-anaemia cohort). In patients with anaemia, 71.0% were aware of the relationship between CKD and anaemia versus 52.9% of those in the non-anaemia cohort. In the anaemia cohort, 46.3% of patients were aware of their haemoglobin level, compared with 27.2% of patients in the non-anaemia cohort. Symptoms most commonly reported as being made worse by anaemia included lack of energy (82.4%), feeling ill (31.4%), and the ability to enjoy life (30.2%). Despite 67.4% of patients with anaemia in CKD believing that their condition was well or very well managed, only 50% reported being informed about different treatments without having to prompt their healthcare professional, and 43.9% were seeking more information and support about managing their condition. Conclusions In the United States, patients with anaemia and CKD perceived that anaemia had a negative impact on their physical health and emotional wellbeing. Our findings emphasize the lack of disease awareness regarding anaemia in patients with CKD, suggesting that patients would benefit from further education regarding its management, and available treatment options.

Introduction The aim of the study was to compare glycemic and weight change outcomes for type 2 diabetes patients treated with either exenatide once-weekly (EQW) or exenatide twice-daily (EBID) with those patients treated with basal insulin (BI). Methods Retrospective data (2010–2014) were extracted from the Clinical Practice Research Datalink, a UK primary care database. Patients previously naïve to injectable therapy initiating EQW, EBID, or BI were extracted and matched by propensity score within two analyses (EQW vs BI and EBID vs BI). Absolute and relative change in HbA1c and weight from baseline and the proportion of patients achieving HbA1c ≤ 7.0% (53 mmol/mol) combined with weight reduction targets of (1) any weight loss or (2) ≥ 5.0% from baseline were compared at 6 and 12–24 months. Results A total of 485 patients initiated EQW, 3573 EBID, and 13,503 BI. In the propensity matched EQW versus BI analysis, mean HbA1c decreased with changes of − 1.33% (− 14.5 mmol/mol) and − 1.24% (− 13.5 mmol/mol) at 6 months and − 1.19% (− 13.0 mmol/mol) and − 1.17% (− 12.8 mmol/mol) at 12–24 months, respectively. Respective weight change was − 3.7 kg versus + 1.2 kg (p

Methods for discrete choice experiment (DCE) attribute and attribute-level selection have not yet been firmly established and are rarely reported in detail. This paper describes a qualitative study designed to inform the development of a DCE survey designed to examine preferences for glucagon-like peptide-1 receptor agonist (GLP-1RA) treatments among patients with type 2 diabetes mellitus. The study involved a literature review, interviews with clinical experts, and interviews with GLP-1RA-experienced (i.e., exenatide once weekly, liraglutide once daily) and injection-naive type 2 diabetes patients from Brazil, China, Germany, Japan, and the UK. Interviews followed a semi-structured guide including open-ended questions, and probes to capture the patients’ perspective on important aspects of GLP-1RAs and concerns with injectable treatments. Qualitative analyses were performed utilizing MAXQDA version 11. Descriptive statistics were used to summarize the sample. Thirty-two articles were reviewed, including 13 DCE studies. Thirty-one attributes were identified from the DCE studies, and 61 different attributes were identified in the non-DCE studies. Fifty patients completed interviews: 28 (56%) GLP-1RA-experienced and 22 (44%) injection-naive, 54% were male, and they had a mean age of 52.8 years. Patients considered efficacy, adverse effects, and dosing frequency as the most important treatment-related attributes. From a list of five pre-defined device- or regimen-related attributes, patients considered dosing frequency, needle size, and injection preparation as the three most important attributes. This study adds to the DCE literature to inform researchers on attribute selection methodology in an international setting as there is limited published information to guide researchers on best practices for selecting and defining attributes for DCE surveys.

Introduction This study assessed the relative importance of treatment-related attributes in influencing patient preferences for glucagon-like peptide-1 receptor agonists (GLP-1RAs) among injection-experienced type 2 diabetes mellitus (T2DM) patients in Germany and the United Kingdom. Methods T2DM patients experienced with injecting once-weekly (QW) exenatide or once-daily (QD) liraglutide completed an online discrete-choice experiment (DCE) survey. Patients chose between hypothetical blinded treatment profiles reflecting attributes of GLP-1RAs. The DCE survey included eight attributes: efficacy, side effects, device size, needle size, titration, injection preparation, long-term efficacy/safety, and dosing frequency. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a conditional logit model indicating the likelihood of choosing a treatment with a given attribute level versus a reference attribute level. Results 510 GLP-1RA injection-experienced patients completed the survey; 45.3% respondents were being treated with exenatide QW and 54.7% respondents were being treated with liraglutide QD. In terms of GLP-1RA attributes, patients indicated a preference for a treatment with greater efficacy (i.e., a 1.5-point improvement in HbA1c) (OR 2.58; 95% CI 2.37, 2.80; p

Background and objectives Despite the growing body of evidence characterising the association between serum potassium levels and adverse clinical outcomes, a contemporary summary of available evidence is currently lacking. The objective of this study, therefore, was to undertake a systematic literature review to identify all relevant evidence assessing risk factors associated with the incidence of hyperkalaemia (HK) and also quantifying the effect of serum potassium levels on risk of adverse clinical outcomes. Methods PubMed (Medline and Medline In-Process), Embase and the Cochrane Library were searched for studies published between January 2002 and November 2018. Search inclusion criteria included studies describing either the incidence of HK events and any associated risk factors, or associations between HK or serum potassium concentration and adverse clinical outcomes including mortality, hospitalisation, major adverse cardiac events (MACE) and renin-angiotensin-aldosterone system inhibitors (RAASi) discontinuation in adult patients with chronic kidney disease (CKD), heart failure (HF), type 2 diabetes (T2DM) or hypertension. Results The search identified 1,897 publications. From these, a total of 123 studies met the inclusion criteria and were included in the review. The most commonly identified risk factors associated with HK events were the presence of CKD or renal impairment, T2DM, HF, hypertension, RAASi use and mineralocorticoid receptor antagonist use. Potassium levels both above and below the normal range were consistently associated with adverse clinical outcomes, with relative and absolute risks of outcomes increasing with severity of hyper- or hypokalaemia. These associations were consistently reported across a broad range of patient population types and study types. Conclusion The current body of published evidence is compelling in its confirmation of the associations between serum potassium levels and adverse clinical outcomes. This review further highlights the importance of avoiding both hyper- and hypokalaemia, in order to reduce risk of mortality, hospitalisation, MACE and RAASi discontinuation or down-titration.

Background: The aim was to investigate real-world treatment outcomes and tolerability of GLP-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes in Germany. Methods: Patients from 323 primary care practices who started any GLP-1RA therapy (89 Byetta, 108 Bydureon, 347 Victoza patients) between January 1, 2011, and December 31, 2013 (index date) were analyzed retrospectively (Disease Analyzer database, Germany). Changes from baseline in HbA1c, weight, and hypoglycemia were evaluated in 3 follow-up periods of 0-6, 7-12, and 13-18 months. Results: A total of 544 diabetes patients (mean age: 57.9 years; men: 54%) were eligible for the study. Mean (SD) HbA1c (%) decreased from 8.3 (1.4) at baseline to 7.4 (1.2) in 6 months, 7.6 (1.3) in 7-12 months and 7.6 (1.4) in 13-18 months, respectively ( P < .001 for all), while the proportion of patients with HbA1c Conclusions: In clinical practice, GLP-1RA treatment was associated with improved glycemic control without increased hypoglycemia for up to 18 months. The higher the baseline HbA1c, the greater the HbA1c reduction recorded.

To assess the cost-effectiveness of exenatide 2 mg once-weekly (EQW) compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg and 1.8 mg once-daily (QD), and lixisenatide 20 μg QD for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin.The Cardiff Diabetes Model was applied to evaluate cost-effectiveness, with treatment effects sourced from a network meta-analysis. Quality-adjusted life years (QALYs) were calculated with health-state utilities applied to T2DM-related complications, weight changes, hypoglycemia, and nausea. Costs (GBP £) included drug treatment, T2DM-related complications, severe hypoglycemia, nausea, and treatment discontinuation due to adverse events. A 40-year time horizon was used.In all base-case comparisons, EQW was associated with a QALY gain per patient; 0.046 vs dulaglutide 1.5 mg; 0.102 vs liraglutide 1.2 mg; 0.043 vs liraglutide 1.8 mg; and 0.074 vs lixisenatide 20 μg. Cost per patient was lower for EQW than for liraglutide 1.8 mg (-£2,085); therefore, EQW dominated liraglutide 1.8 mg. The cost difference per patient between EQW and dulaglutide 1.5 mg, EQW and liraglutide 1.2 mg, and EQW and lixisenatide 20 μg was £27, £103, and £738, respectively. Cost per QALY gained with EQW vs dulaglutide 1.5 mg, EQW vs liraglutide 1.2 mg, and EQW vs lixisenatide 20 μg was £596, £1,004, and £10,002, respectively. In the probabilistic sensitivity analysis, the probability that EQW is cost-effective ranged from 76-99%.Results suggest that exenatide 2 mg once-weekly is cost-effective over a lifetime horizon compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg QD, liraglutide 1.8 mg QD, and lixisenatide 20 μg QD for the treatment of T2DM in adults not adequately controlled on metformin alone.

Qing Qiao,1 Mario JNM Ouwens,1 Susan Grandy,2 Kristina Johnsson,1 Karel Kostev3 1Global Medicines Development, AstraZeneca, Gothenburg, Sweden; 2Global Medicines Development, AstraZeneca, Gaithersburg, MD, USA; 3Epidemiology and Evidence-Based Medicine, Real-World Evidence Solutions, IMS Health, Frankfurt am Main, Germany Aim: This study aimed to compare 6-month adherence to therapy with exenatide once weekly (Bydureon®) vs liraglutide once daily (Victoza®) in patients with type 2 diabetes under primary care in Germany.Methods: A nationwide longitudinal prescription database (LRx), (between January 2011 and September 2014) was used to analyze adherence to therapy. The proportion of days covered (PDC) by prescription was used as a measure of adherence in the 6-month postindex period. Logistic regression analyses were performed to investigate the associations between glucagon-like peptide-1 receptor agonist therapy adjusting for age, sex, and cotherapy.Results: Therapy was initiated in 5,449 patients with exenatide once weekly (age: 59.7±11.8years; 51.4% were male) and in 24,648 patients with liraglutide once daily (age: 59.4±11.4years; 49.7% were male). The median PDC was 0.88 for exenatide once weekly and 0.77 for liraglutide once daily (P

Introduction Exenatide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA), approved for treatment of type 2 diabetes mellitus (T2DM). There is limited direct evidence comparing the efficacy and tolerability of exenatide 2 mg once weekly (QW) to other GLP-1 RAs. A network meta-analysis (NMA) was conducted to estimate the relative efficacy and tolerability of exenatide QW versus other GLP-1 RAs for the treatment of adults with T2DM inadequately controlled on metformin monotherapy. Methods A systematic literature review was conducted to identify randomized controlled trials (RCTs) that investigated GLP-1 RAs (albiglutide, dulaglutide, exenatide, liraglutide, and lixisenatide) at approved doses in the United States/Europe, added on to metformin only and of 24 ± 6 weeks treatment duration. A Bayesian NMA was conducted. Results Fourteen RCTs were included in the NMA. Exenatide QW obtained a statistically significant reduction in glycated hemoglobin (HbA1c) relative to lixisenatide 20 µg once daily. No other comparisons of exenatide QW to other GLP-1 RAs were statistically significant for change in HbA1c. No statistically significant differences in change in weight, systolic blood pressure, risk of nausea or discontinuation due to adverse events were observed for exenatide QW versus other GLP-1 RAs. Conclusion Exenatide QW demonstrated similar effectiveness and tolerability compared to other GLP-1 RAs, for the treatment of T2DM in adults inadequately controlled on metformin alone. Electronic supplementary material The online version of this article (doi:10.1007/s13300-016-0155-1) contains supplementary material, which is available to authorized users.

Background Hyperkalaemia is a potentially life-threatening condition that can be managed with pharmacological and non-pharmacological approaches. With the recent development of new hyperkalaemia treatments, new information on safe and effective management of hyperkalaemia has emerged. Objectives This systematic literature review (SLR) aimed to identify all relevant comparative and non-comparative clinical data on management of hyperkalaemia in adults. Our secondary aim was to assess the feasibility of quantitatively comparing randomised controlled trial (RCT) data on the novel treatment sodium zirconium cyclosilicate (ZS) and established pharmacological treatments for the non-emergency management of hyperkalaemia, such as the cation-exchangers sodium/calcium polystyrene sulphonate (SPS/CPS). Methods MEDLINE, Embase and the Cochrane Library were searched on 3rd April 2017, with additional hand-searches of key congresses and previous SLRs. Articles were screened by two independent reviewers. Eligible records reported interventional or observational studies of pharmacological or non-pharmacological management of hyperkalaemia in adults. Results Database searches identified 2,073 unique records. Two hundred and one publications were included, reporting 30 RCTs, 29 interventional non-RCTs and 43 observational studies. Interventions investigated in RCTs included ZS (3), SPS/CPS (3), patiromer (4) and combinations of temporising agents (6 RCTs). A robust and meaningful indirect treatment comparison between ZS and long-established cation-binding agents (SPS/CPS) was infeasible because of heterogeneity between studies (including time points and dosing) and small sample size in SPS/CPS studies. Conclusions Despite hyperkalaemia being associated with several chronic diseases, there is a paucity of high-quality randomised evidence on long-established treatment options (SPS and CPS) and a limited evidence base for hyperkalaemia management with these agents.

Introduction This study aimed to determine if data mining methodologies could identify reproducible predictors of dapagliflozin-specific treatment response in the phase 3 clinical program dataset. Methods Baseline and early treatment response variables were selected and data mining used to identify/rank all variables associated with reduction in glycated hemoglobin (HbA1c) at week 26. Generalized linear modeling was then employed using an independent dataset to identify which (if any) variables were predictive of dapagliflozin-specific treatment response as compared with treatment response in the study’s control arm. The most parsimonious (i.e., simplest) model was validated by meta-analysis of nine other trials. This staged approach was used to minimize risk of type I errors. Results From the large dataset, 22 variables were selected for model generation as potentially predictive for dapagliflozin-specific reduction in HbA1c. Although baseline HbA1c was the variable most strongly associated with reduction in HbA1c at study end (i.e., the best prognostic variable), baseline fasting plasma glucose (FPG) was the only predictive dapagliflozin-specific variable in the model. Placebo-adjusted treatment effect of dapagliflozin plus metformin vs. metformin alone for change in HbA1c from baseline was −0.65% at the average baseline FPG of 192.3 mg/dL (10.7 mmol/L). This response changed by −0.32% for every SD [57.2 mg/dL (3.2 mmol/L)] increase in baseline FPG. Effect of baseline FPG was confirmed in the meta-analysis of nine studies, but the magnitude was smaller. No other variable was independently predictive of a dapagliflozin-specific reduction in HbA1c. Conclusions This methodology successfully identified a reproducible baseline predictor of differential response to dapagliflozin. Although baseline FPG was shown to be a predictor, the effect size was not of sufficient magnitude to suggest clinical usefulness in identifying patients who would uniquely benefit from dapagliflozin treatment. The findings do support potential benefit for dapagliflozin treatment that is consistent with current recommended use. Electronic supplementary material The online version of this article (doi:10.1007/s13300-014-0090-y) contains supplementary material, which is available to authorized users.

Aims This study evaluated change in health-related quality of life (HRQOL) associated with ongoing weight change among patients with type 2 diabetes mellitus (T2DM) treated with dapagliflozin, a highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that lowers blood glucose by increasing urinary glucose excretion and is associated with body weight reductions. Methods Patients with T2DM who had inadequate glycaemic control on metformin (MET) alone were enrolled in a 24-week, double-blind, randomized, placebo-controlled study with a 78-week extension to evaluate the effect of dapagliflozin + MET on body weight. Patients also completed the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes Weight Questionnaire-9 (SHIELD-WQ-9), a weight change-related HRQOL survey. Difference in proportions of patients treated with dapagliflozin 10 mg + MET (n = 89) or placebo + MET (n = 91) who reported improvement in HRQOL was analysed with Fisher's exact test. Results Dapagliflozin patients had significantly greater weight loss than placebo patients over 102 weeks (p

Objectives: This study evaluated the association between weight loss and change in depression among patients with type 2 diabetes mellitus (T2DM). Methods: Weight change from 2008 to 2009 among respondents (with and without T2DM) in the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) was calculated. Change in depression was calculated as change from 2008 to 2009 in Patient Health Questionnaire-9 (PHQ-9) scores. Respondents with weight loss (>1%, >3%, >5%) were compared with respondents with weight gain (≥1%). Multivariate regression adjusted for baseline characteristics. Results: Among those with T2DM, more respondents with weight loss (n = 779) improved their depression scores, compared with respondents with weight gain (n = 731): 32.9%, 36.9%, 39.8% for >1%, >3%, and >5% weight loss, respectively, vs. 28.7% for weight gain (p1%, 2.96 for >3%, and 3.31 for >5% weight loss, p

SUMMARY Aims: This study compared health-related quality of life (HRQOL) in adults with type 2 diabetes mellitus (T2DM) who reported their perception of weight change vs. actual weight change. Methods: Respondents to the US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) 2008 survey were asked if they had lost, maintained or gained weight compared with 1 year earlier (perception). Respondents also provided their actual weight and completed the SHIELD WQ-9 questionnaire to report how weight change affected 9 aspects of daily life. Perceived weight loss or gain was compared with measured weight change reported (2007 weight – 2008 weight) in those with T2DM. Results: In respondents reporting weight loss (n = 762), 75.4% lost weight and 15.9% gained weight. For respondents reporting weight gain (n = 392), 70.2% gained weight and 19.6% lost weight. HRQOL did not differ between those who reported weight loss and actually lost weight vs. those who reported weight loss and actually gained weight (p > 0.05), except for selfesteem (p = 0.004). HRQOL was similar for those who reported weight gain and actually gained weight vs. those who reported weight gain, but actually lost weight (p > 0.20). Respondents who had perceived weight loss had significantly better HRQOL than those who perceived that they had gained weight. Conclusions: Perception of weight loss/gain may be as powerful as actual weight loss/ gain in impacting HRQOL among adults with T2DM. Interventions that help individuals lose weight or perceive weight loss in addition to lowering glucose will assist in improving HRQOL. What’s known There has been a dramatic increase in diabetes and obesity worldwide during the last decade. Weight loss is associated with improvements in glycaemic control among adults with type 2 diabetes mellitus. Weight loss is associated with improvements in health-related quality of life among individuals who are overweight or obese. What’s new This study provides evidence that self-perception of weight change impacts health-related quality of life in the same manner as actual weight loss or weight gain among adults with type 2 diabetes mellitus. Additionally, this study adds to the scarce data available for type 2 diabetes mellitus and the impact of weight change on quality of life among these individuals.

Background: Adherence to prescribed diabetes medications is suboptimal, which can lead to poor glycemic control and diabetic complications. Treatment-related weight gain is a side effect of some oral antidiabetic agents and insulin, which may negatively affect adherence to therapy. Objective: This study investigated whether adults with type 2 diabetes mellitus (T2DM) who lost weight had better medication adherence than those who gained weight. Methods: Weight change over 1 year (2007 to 2008) was assessed among respondents in the US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD). Weight loss of 41.0%, Z3%, and Z5% of weight was compared with weight gain of Z1.0%. Medication adherence was assessed using the Morisky 4-item questionnaire for medication-taking behavior, with lower scores representing better adherence. Results: There were 746 T2DM respondents who lost 41.0%, 483 who lost Z3%, 310 who lost Z5%, and 670 who gained Z1.0% of weight. Each weight-loss group had significantly lower Morisky scores than the weight-gain group; mean scores of 0.389 versus 0.473 (P ¼ 0.050) for the 41.0% weight-loss group, 0.365 versus 0.473 (P ¼ 0.026) for the Z3% weight-loss group, and 0.334 versus 0.473 (P ¼ 0.014) for the Z5% weight-loss group. Significantly fewer respondents who lost weight had received insulin, sulfonylurea, or thiazolidinedione therapy (57%) compared with respondents who gained weight (64%) (P ¼ 0.002). Demographics, exercise habits, and dieting were similar between weight-loss and weightgain groups. Conclusions: T2DM respondents with weight loss had significantly better medication adherence and were less likely to be on treatment regimens that increase weight than T2DM respondents with weight gain. These findings suggest that strategies that lead to weight loss, including use of diabetes medications associated with weight loss, may improve medication adherence.

Introduction Glucagon-like peptide-1 receptor agonists (GLP-1RAs) differ in efficacy, side effects, dosing frequency, and device-related attributes. This study assessed the relative importance of treatment-related attributes in influencing preferences for GLP-1RAs among injection-naïve patients with type 2 diabetes mellitus (T2DM). Methods Injection-naïve T2DM patients from five countries completed a Web-based discrete choice experiment (DCE) survey. Patients chose between hypothetical treatment profiles reflecting important and differentiating attributes of GLP-1RAs. Eight attributes were included: efficacy, side effects, device size, needle size, titration, preparation, evidence of long-term efficacy/safety, and dosing frequency. Odds ratios (ORs) and 95% confidence intervals were calculated using a conditional logit model to indicate the likelihood of choosing a treatment with a given attribute level versus a reference attribute level. The influence of individual attributes when considering full treatment profiles was examined using exenatide once weekly (QW) and liraglutide once daily (QD) as case examples. Results A total of 1482 patients with T2DM completed the DCE survey. Side effects, efficacy, and dosing frequency were the three most important attributes influencing preferences; needle size, device size, and required preparation were least important. Total sample analysis indicated that a profile of GLP-1RA approximating exenatide QW (single pen) was preferred over a profile approximating liraglutide QD (OR 3.36; p

Aims To investigate real-world clinical and patient-related variables associated with initiating GLP-1 receptor agonist (GLP-1RA) treatment relative to initiation of other glucose-lowering therapies in type 2 diabetes (T2D) patients of primary care in Germany. Methods Data for 938 T2D patients who started therapy with a GLP-1RA within 823 practices of primary care throughout Germany were retrospectively analyzed (Disease Analyser: 01/2011–03/2014). 5,197 T2D patients who initiated other non-GLP-1RA antidiabetic therapies were selected as controls. Multivariate logistic regression analyses were applied to identify factors associated with GLP-1RA initiation in primary care. Results Mean age (SD) of GLP-1RA users was 57.8 (11.8) years (males: 55.5%) and the average BMI was 36.1 (6.7) kg/m2. 22.8% were in diabetologist care and 12.0% had private health insurance. In multivariate regression, choice of GLP-1RA therapy instead of a different glucose-lowering drug class was associated with obesity (odds ratio: 1.68; 95% CI: 1.34–2.10), private health insurance (2.42; 1.89–3.09), younger age (0.94; 0.93–0.95 per year), male sex (0.85; 0.73–0.99), diabetologist care (2.11; 1.73–2.57), and geographic practice location (East vs. West-Germany; 1.25; 1.05–1.49). Among co-medication, angiotensin II antagonists (increased) and non-steroidal antirheumatic agents (decreased) were related to GLP-1RA prescriptions (both p

Increased visceral adipose tissue (VAT) is "pathogenic" through adverse endocrine and immune contributions to metabolic diseases such as diabetes mellitus, hypertension, and dyslipidemia. Increased VAT increases waist circumference (WC), and WC is a recommended anthropometric measure of pathogenic adipose tissue distribution. Increased subcutaneous adipose tissue (SAT) is often described as "protective" against metabolic disease and frequently approximated by hip circumference (HC).The Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) evaluated a study sample weighted to reflect the U.S. adult population. Respondents diagnosed with type 2 diabetes mellitus (T2DM; n = 3825) and without T2DM (n = 13,327) self-reported their weight and height, WC, and HC.T2DM men and women had a disproportionate increase in body mass index (BMI) and WC, with 30% of T2DM men and 40% of T2DM women having a WC within the highest quintile compared to the overall study population. Waist-to-hip ratio (WHR) appeared to be the best anthropometric predictor of T2DM. However, both T2DM men and women also had a disproportionate increase in HC, with 30% of T2DM men and 34% of T2DM women having a HC within the highest quintile, which was generally similar to the distribution of BMI and WHR.This analysis suggests that: (1) An increase in adipose tissue generally increases the risk of T2DM; (2) central adiposity is more pathogenic than peripheral subcutaneous adiposity; and (3) SAT accumulation, as assessed by increased HC, does not always "protect" against metabolic diseases such as T2DM.

RECURRENT HYPERKALAEMIA AND ASSOCIATION WITH LENGTH-OF-STAY AND MORTALITY FOLLOWING HOSPITALISATION : REAL-WORLD EVIDENCE FROM UK PATIENTS WITH CKD

RELATIONSHIP BETWEEN HYPERKALAEMIA AND DOWN-TITRATION OR DISCONTINUATION OF RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS IN UK PATIENTS WITH CKD

This study evaluated whether positive health attitudes were associated with healthy behaviors in individuals with cardiovascular disease (CVD) or moderate coronary heart disease (CHD) risk. Self-reported health attitudes and behaviors were assessed in the US Study to Help Improve Early Evaluation and Management of Risk Factors Leading to Diabetes (SHIELD) for respondents with CVD and type 2 diabetes mellitus (very high risk), CVD and no diabetes (high risk), or moderate CHD risk. CVD was defined as a diagnosis of heart disease/heart attack, stroke, obstructed coronary arteries, or revascularization. Moderate CHD risk was defined as >/=2 Framingham risk factors. Comparisons across very high-risk (n=1177), high-risk (n=2202), and moderate-risk (n=6802) respondents were made using analysis of variance. The proportion of respondents reporting excellent or very good current health decreased with increasing risk (37% of moderate-risk, 21% of high-risk, and 13% of very high-risk respondents). The proportion concerned that their health problems might worsen increased with increasing risk (55%, 63%, and 74%). With increasing risk, 28%, 26%, and 31% exercised regularly and 58%, 52%, and 54% maintained their desired weight for >6 months. Respondents with positive health attitudes were more likely to exercise regularly and maintain desired weight compared with respondents with negative health attitudes (P