Understanding Patient Perspectives of the Impact of Anemia in Chronic Kidney Disease: A United States Patient Survey.

Anemia in chronic kidney disease (CKD) is associated with reduced health-related quality of life and physical functioning. This study investigated knowledge and awareness of anemia in patients with CKD in the United States (US) through an online, quantitative survey administered to patients aged ≥18 years with self-reported CKD, with or without anemia. Of 446 patients included, 255 (57.2%) were diagnosed with anemia and 191 (42.8%) were in the non-anemia cohort. In patients with anemia, 71.0% were aware of the relationship between CKD and anemia versus 52.9% in the non-anemia cohort. In the anemia cohort, 46.3% of patients were aware of their hemoglobin level, versus 27.2% in the non-anemia cohort. Despite 67.4% of patients with anemia believing their condition was well/very well managed, only 50% reported being informed about different treatments without prompting healthcare providers. In the US, patients with anemia and CKD perceived that anemia had a negative impact on physical health and emotional wellbeing. Results emphasize a lack of disease awareness, suggesting patients would benefit from further education on anemia in CKD.

Health-related quality of life and lifestyle changes in patients with chronic kidney disease and hyperkalaemia: Real-world data from the US, five European countries and China.

BACKGROUND: Chronic kidney disease patients have impaired health-related quality of life and an increased risk of hyperkalaemia. AIMS: The objective was to evaluate the impact of hyperkalaemia on health-related quality of life, and investigate lifestyle change recommendations, in these patients. METHODS: The Adelphi Real World Chronic Kidney Disease Specific Programme™ was used. Data were collected from physicians and patients with non-dialysis dependent stage 3a, 3b and 4 chronic kidney disease from the US, France, Germany, Spain, Italy, the UK and China. Patients completed the Kidney Disease Quality of Life Instrument and EuroQol-5D-3L. Analyses compared data between hyperkalaemic (serum potassium >5.0 mmol/L) and normokalaemic (serum potassium 3.5-5.0 mmol/L) patients. RESULTS: Overall, 1149 patients were included (hyperkalaemic: n = 216, normokalaemic: n = 933; US: n = 376, Europe: n = 490, China: n = 283). Hyperkalaemic vs normokalaemic patients experienced more symptoms (P < .001) and had numerically lower scores, indicating poorer health-related quality of life, in all Kidney Disease Quality of Life domains, with significant differences for three/five domains. Hyperkalaemic patients reported numerically lower EuroQol-5D-3L utility index and visual analogue scores, indicating poorer health status, than normokalaemic patients. A higher proportion of hyperkalaemic than normokalaemic patients were recommended to reduce dietary potassium (P < .05). More normokalaemic than hyperkalaemic patients reported making a radical change in five/six recommended lifestyle changes, with the difference significant for four/six recommendations. CONCLUSIONS: Hyperkalaemia is associated with an incremental impairment of the health-related quality of life in chronic kidney disease patients. A better understanding of the impact of hyperkalaemia in these patients could improve patient outcomes.

Understanding Patient Perspectives and Awareness of the Impact and Treatment of Anemia with Chronic Kidney Disease: A Patient Survey in China.

BACKGROUND: 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.

The Impact of CKD Anaemia on Patients: Incidence, Risk Factors, and Clinical Outcomes-A Systematic Literature Review.

Anaemia is a common consequence of chronic kidney disease (CKD); however, the risk factors for its development and its impact on outcomes have not been well synthesised. Therefore, we undertook a systematic review to fully characterise the risk factors associated with the presence of anaemia in patients with CKD and a contemporary synthesis of the risks of adverse outcomes in patients with CKD and anaemia. We searched MEDLINE, EMBASE, and the Cochrane Library from 2002 until 2018 for studies reporting the incidence or prevalence of anaemia and associated risk factors and/or associations between haemoglobin (Hb) or anaemia and mortality, major adverse cardiac events (MACE), hospitalisation, or CKD progression in adult patients with CKD. Extracted data were summarised as risk factors related to the incidence or prevalence of anaemia or the risk (hazard ratio (HR)) of outcome by Hb level (<10, 10-12, >12 g/dL) in patients not on dialysis and in those receiving dialysis. 191 studies met the predefined inclusion criteria. The risk factor most associated with the prevalence of anaemia was CKD stage, followed by age and sex. Mean HRs (95% CI) for all-cause mortality in patients with CKD on dialysis with Hb <10, 10-12, and >12 g/dL were 1.56 (1.43-1.71), 1.17 (1.09-1.26), and 0.91 (0.87-0.96), respectively. Similar patterns were observed for nondialysis patients and for the risks of hospitalisation, MACE, and CKD progression. This is the first known systematic review to quantify the risk of adverse clinical outcomes based on Hb level in patients with CKD. Anaemia was consistently associated with greater mortality, hospitalisation, MACE, and CKD progression in patients with CKD, and risk increased with anaemia severity. Effective treatments that not only treat the anaemia but also reduce the risk of adverse clinical outcomes are essential to help reduce the burden of anaemia and its management in CKD.

Associations between serum potassium and adverse clinical outcomes: A systematic literature review.

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.

Glucose Control and Weight Change Associated with Treatment with Exenatide Compared with Basal Insulin: A Retrospective Study.

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 < 0.001) and - 3.2 kg versus + 2.5 kg (p < 0.001). Significantly more EQW patients achieved the combined HbA1c ≤ 7.0% (53 mmol/mol) and weight loss target (22.4% versus 9.9% at 6 months and 18.2% versus 8.0% at 12-24 months, respectively) and HbA1c ≤ 7.0% (53 mmol/mol) and minimum 5% weight loss (11.8% versus 3.7% at 6 months, and 8.0% versus 0.0% at 12-24 months). For EBID versus BI, similar results were found. CONCLUSION: In this real-world data analysis, exenatide QW and exenatide BID were associated with similar glycemic control and greater weight reduction compared with basal insulin.

Evidence in support of hyperkalaemia management strategies: A systematic literature review.

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.

Discrete Choice Experiment Attribute Selection Using a Multinational Interview Study: Treatment Features Important to Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: 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. METHODS: 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-naïve 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. RESULTS: 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-naïve, 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. CONCLUSION: 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.

Glucagon-Like Peptide-1 Receptor Agonist Treatment Attributes Important to Injection-Experienced Patients with Type 2 Diabetes Mellitus: A Preference Study in Germany and the United Kingdom.

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 < 0.001), fewer side effects (OR 2.67; 95% CI 2.52, 2.82; p < 0.001), once-weekly rather than once-daily administration (OR 2.26; 95% CI 2.13, 2.39; p < 0.001), and the preparation required for a multi-use pen (OR 1.71; 95% CI 1.55, 1.88; p < 0.001). Needle size, device size, and titration were not significant drivers of patient preference. CONCLUSIONS: Among GLP-1RA injection-experienced patients, key drivers of treatment preference for a hypothetical GLP-RA profile were side effects, efficacy, dosing frequency, and required preparation. Understanding patient preferences is important for optimizing treatment decision-making and improving treatment adherence. FUNDING: AstraZeneca.

Glucagon-like Peptide-1 Receptor Agonist Treatment Attributes Important to Injection-Naïve Patients with Type 2 Diabetes Mellitus: A Multinational Preference Study.

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 < 0.001), when efficacy was assumed to be equal. CONCLUSION: The most influential drivers of treatment preferences for a hypothetical GLP-RA profile were side effects, efficacy, and dosing frequency among injection-naïve T2DM patients. Preference elicitation can promote patient-centered care and inform new generations of T2DM treatments, which can lead to improved adherence and health outcomes.

Treatment Outcomes and Tolerability Following Initiation of GLP-1 Receptor Agonists Among Type 2 Diabetes Patients in Primary Care Practices in Germany.

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 <7% increased from 15% at baseline to 38%, 36% and 35% in the corresponding periods ( P < .0001 for all). Multivariate-adjusted beta coefficients corresponding to changes in HbA1c (%) from baseline were -.52, -.44, and -.44, respectively, in the follow-up periods for baseline HbA1c (%) ( P < .0001 for all). The prevalence of hypoglycemia at baseline was 0.7%; this did not change significantly after treatment. 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.

Adherence to GLP-1 receptor agonist therapy administered by once-daily or once-weekly injection in patients with type 2 diabetes in 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±11.8 years; 51.4% were male) and in 24,648 patients with liraglutide once daily (age: 59.4±11.4 years; 49.7% were male). The median PDC was 0.88 for exenatide once weekly and 0.77 for liraglutide once daily (P<0.05). Once-weekly exenatide was associated with significantly higher adherence. Odds ratio (95% confidence interval) for having a PDC of ≥0.80 was 1.78 (1.62-1.96) for exenatide once weekly compared with liraglutide once daily after adjusting for age, sex, and cotherapy. CONCLUSION: Adherence to treatment with exenatide once weekly was significantly increased compared to that with liraglutide once daily over 6 months in patients with type 2 diabetes.

Clinical and Patient-Related Variables Associated with Initiating GLP-1 Receptor Agonist Therapy in Type 2 Diabetes Patients in Primary Care in Germany.

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<0.001). CONCLUSIONS: Consistent with German guidelines, GLP-1RA is mainly prescribed preferentially in T2D patients who are obese. GLP-1RA drugs were more frequently used than other options in privately health insured patients and in patients seeing a diabetologist.

A Network Meta-analysis Comparing Exenatide Once Weekly with Other GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus.

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.

Patient Characteristics are not Associated with Clinically Important Differential Response to Dapagliflozin: a Staged Analysis of Phase 3 Data.

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.

Association of Weight Loss and Medication Adherence Among Adults With Type 2 Diabetes Mellitus: SHIELD (Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes).

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 >1.0%, ≥3%, and ≥5% of weight was compared with weight gain of ≥1.0%. 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 >1.0%, 483 who lost ≥3%, 310 who lost ≥5%, and 670 who gained ≥1.0% 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 = 0.050) for the >1.0% weight-loss group, 0.365 versus 0.473 (P = 0.026) for the ≥3% weight-loss group, and 0.334 versus 0.473 (P = 0.014) for the ≥5% 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 = 0.002). Demographics, exercise habits, and dieting were similar between weight-loss and weight-gain 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.

Change in health status (EQ-5D) over 5 years among individuals with and without type 2 diabetes mellitus in the SHIELD longitudinal study.

BACKGROUND: Health-related quality of life studies among adults with type 2 diabetes mellitus, using the EQ-5D, have been short term and have not assessed change over years. This study assessed the change in health status and health-related quality of life over 5 years among individuals with and without diabetes. METHODS: Respondents to the US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) completed the EuroQol-5D (EQ-5D) at baseline (2004) and 5 years later (2009). Visual analog scale (VAS) score and health index score were computed at baseline and year 5, and the change over 5 years was measured for individuals with type 2 diabetes mellitus (T2DM) and those without diabetes, and T2DM adults with and without diabetic complications. Linear regression models were used to determine change in EQ-5D score, controlling for age, gender, race, education, household income, and body mass index (BMI). RESULTS: There was significantly greater decline in the EQ-5D index score in the T2DM group (-0.031 [SD 0.158]), compared with those without diabetes (-0.016 [0.141], p = 0.001). Compared with respondents without diabetes, those with T2DM had a larger reduction in EQ-5D index score, after controlling for demographics (p = 0.001). EQ-5D VAS score declined over 5 years for both groups: -1.42 (18.1) for the T2DM group, and -0.63 (15.8) for the group without diabetes, but the between-group difference was not significant either before (p = 0.09) or after (p = 0.12), controlling for demographics. T2DM respondents with diabetic complications had a greater decline in EQ-5D scores than T2DM respondents without complications (p < 0.05). CONCLUSION: Over a 5-year period, health status of respondents with T2DM declined significantly compared with those with no diabetes, indicating that the burden of the disease has a long-term detrimental impact. This decline in health status is likely to impact utility scores (fewer quality-adjusted life years) for economic evaluations.

Quality of Life, Depression, and Healthcare Resource Utilization among Adults with Type 2 Diabetes Mellitus and Concomitant Hypertension and Obesity: A Prospective Survey.

Background. This study compared quality of life, depression, and healthcare resource utilization among adults with type 2 diabetes mellitus (T2DM) and comorbid hypertension (HTN) and obesity with those of adults reporting T2DM alone. Methods. Respondents to the US SHIELD survey self-reported their height, weight, comorbid conditions, hospitalizations, and outpatient visits and completed the Short Form-12 (SF-12) and Patient Health Questionnaire (PHQ-9). Respondents reporting T2DM and HTN and obesity (body mass index, BMI, ≥30 kg/m(2)) were compared with a T2DM-alone group. Results. Respondents with T2DM, HTN, and obesity (n = 1292) had significantly lower SF-12 Physical and Mental Component Summary scores (37.3 and 50.9, resp.) than T2DM-alone respondents (n = 349) (45.8 and 53.5, resp., P < 0.0001). Mean PHQ-9 scores were significantly higher among T2DM respondents with comorbid HTN and obesity (5.0 versus 2.5, P < 0.0001), indicating greater depression burden. Respondents with T2DM, HTN, and obesity had significantly more resource utilization with respect to physician visits and emergency room visits but not hospitalizations than respondents with T2DM alone (P = 0.03). Conclusions. SHIELD respondents with comorbid conditions of T2DM, HTN, and obesity reported greater healthcare resource utilization, more depression symptoms, and lower quality of life than the T2DM-alone group.

Association of Self-Reported Weight Change and Quality of Life, and Exercise and Weight Management Behaviors Among Adults with Type 2 Diabetes Mellitus: The SHIELD Study.

Purpose. This study examined the association between self-reported weight change and quality of life, and exercise and weight management behaviors among individuals with type 2 diabetes mellitus (T2DM). Methods. In the US SHIELD study, respondents reported whether they had lost or gained weight compared with 1 year earlier and completed the SHIELD-WQ-9 quality of life questionnaire as well as provided information on their exercise and weight management behaviors in the past 12 months. Results. Sixteen percent of the respondents reported gaining weight (n = 460), and 30% reported losing weight (n = 895). More respondents who reported losing weight exercised regularly, limited calorie and fat intake, and increased fiber, fruit, and vegetable intake compared with respondents who reported gaining weight (P < 0.01). For all nine aspects of daily life, a significantly greater proportion of respondents who reported losing weight reported improved well-being (12%-44%) compared with respondents who reported gaining weight (P < 0.0001). Conclusions. Self-reported weight loss was associated with improved well-being, better exercise, and weight management behaviors among individuals with T2DM.

Self-reported hypoglycemia and impact on quality of life and depression among adults with type 2 diabetes mellitus.

AIMS: This study evaluated the rate of self-reported hypoglycemia and examined the association of hypoglycemia with quality of life and depression among adults with type 2 diabetes mellitus (T2DM). METHODS: Respondents to the 2008 US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) survey were asked the number of times they experienced hypoglycemia in the past 4 weeks and past 12 months. Respondents also completed the short form-12 (SF-12) questionnaire and the patient health questionnaire (PHQ-9). T2DM respondents reporting at least 1 hypoglycemic episode were compared with T2DM respondents who did not report hypoglycemia in the previous 12 months. RESULTS: Of 2718 T2DM respondents, 23% reported experiencing hypoglycemia in the past 12 months. Respondents reporting hypoglycemia (n=627) had significantly lower (p<0.001) SF-12 scores for both physical health (mean±SD: 37.4±12.7 versus 40.9±12.7) and mental health (50.1±11.7 versus 52.4±10.1) compared with those without hypoglycemia (n=2091). Mean PHQ-9 scores were significantly higher (p<0.001) among respondents reporting hypoglycemia (5.2±5.8), compared with respondents who did not report hypoglycemia (3.9±5.0), indicating greater depression burden. CONCLUSION: Self-reported hypoglycemia was prevalent among individuals with T2DM and associated with lower health-related quality of life, and greater burden of depression.