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Objective Weight reduction is a key component of diabetes management in adults with type 2 diabetes mellitus (T2DM), yet the benefits of weight loss in T2DM patients have been difficult to quantify. We examined the medical literature regarding the relationships between weight change and 1) glycemic control and 2) cost and resource use. Methods Systematic searches were conducted in the electronic databases Embase, MEDLINE, and the Cochrane Database of Systematic Reviews to identify publications regarding the impact of weight change on T2DM outcomes from 2007 onward. Identified publications were screened for relevance against predefined eligibility criteria, and methodological approaches and results were extracted. Evidence for the impact of weight change on outcomes was evaluated and used to identify strengths, limitations, and gaps in the current literature. Results The number of studies meeting eligibility criteria for each outcome was: glycemic control (n=38) and cost and resource use (n=11). The relationship between weight change and glycemic control was dependent on the interplay of multiple factors, eg, the weight loss interventions employed, the antidiabetic medication classes used, the time horizon, and baseline BMI and glycemic control. With respect to cost and resource use, the review indicated that savings were associated with weight loss, and increased costs were associated with weight gain. Conclusion Studies regarding weight change in T2DM patients demonstrated varying effects on glycemic control and a positive association with costs and resource use, where weight loss was associated with decreased costs and resource use. Future studies may be able to clarify these relationships.

Aims: The efficacy and safety of oral semaglutide, the first glucagon-like peptide-1 (GLP-1) receptor agonist developed for oral administration for the treatment of type 2 diabetes, was evaluated i...

Introduction Therapeutic inertia refers to the failure to initiate or intensify treatment in a timely manner and is widespread in type 2 diabetes (T2D) despite the well-established importance of maintaining good glycemic control. The aim of this analysis was to quantify the clinical and economic burden associated with poor glycemic control due to therapeutic inertia in patients with T2D in the USA. Methods The IQVIA CORE Diabetes Model was used to simulate life expectancy, costs associated with diabetes-related complications, and lost workplace productivity in US patients. Baseline glycated hemoglobin (HbA1c) levels were 7.0% (53 mmol/mol), 9.0% (75 mmol/mol), 11.0% (97 mmol/mol) 13.0% (119 mmol/mol), or 15.0% (140 mmol/mol), with targets of 6.5% (48 mmol/mol), 7.0% (53 mmol/mol), 8.0% (64 mmol/mol), or 9.0% (75 mmol/mol) depending on baseline HbA1c, across several delayed intensification scenarios (values above target were defined as poor control). The burden associated with intensification delays of 1, 2, 3, 5, and 7 years was estimated over time horizons of 1–30 years. Future costs and clinical benefits were discounted at 3% annually. Results In a population of 13.4 million patients with T2D and baseline HbA1c of 9.0% (75 mmol/mol), delaying intensification of therapy by 1 year was associated with a loss of approximately 13,390 life-years and increased total costs of US dollars (USD) 7.3 billion (1-year time horizon). Longer delays in intensification were associated with a greater economic burden. Delaying intensification by 7 years was projected to cost approximately 3 million life-years and USD 223 billion over a 30-year time horizon. Conclusion Therapeutic inertia is common in routine clinical practice and makes a substantial contribution to the burden associated with type 2 diabetes in the USA. Initiatives and interventions aimed at preventing therapeutic inertia are needed to improve clinical outcomes and avoid excess costs. Electronic Supplementary Material The online version of this article (10.1007/s12325-019-01199-8) contains supplementary material, which is available to authorized users.

Introduction Liraglutide and sitagliptin were compared on glycemic control and all-cause healthcare costs over a 1-year period among older adults with type 2 diabetes (65–89 years) enrolled in a national Medicare Advantage Prescription Drug health plan. Methods This was a retrospective study in which the index date was the first prescription fill for liraglutide or sitagliptin between 25 January 2010 and 31 December 2014. Post-index treatment persistence and glycosylated hemoglobin (HbA1c) at baseline and 1 year (± 90 days) post-index date were required. Patients were excluded if their record included use of insulin during the baseline period. Inverse probability of treatment weighting using stabilized weights was employed with final covariate adjusted regression modeling to estimate the primary outcome (mean change in HbA1c) and secondary outcomes (achieving glycemic goal and costs), each at 1-year post-index date. Results Overall, 3056 patients met the selection criteria, of whom 218 filled prescriptions for liraglutide and 2838 for sitagliptin. Adjusted mean change in HbA1c at 1 year post-index was − 0.42 with liraglutide versus − 0.12 with sitagliptin (P = 0.0012). Adjusted odds of achieving the treatment goals of HbA1c

Introduction Orally administered semaglutide is the first glucagon-like peptide 1 receptor agonist (GLP-1 RA) for oral administration. As head-to-head trials assessing orally administered semaglutide as an add-on to 1–2 oral antidiabetic drugs (OADs) vs other GLP-1 RAs are limited, a network meta-analysis (NMA) was performed to assess the relative efficacy and safety of orally administered semaglutide 14 mg once-daily (QD) vs injectable GLP-1 RAs in patients with type 2 diabetes inadequately controlled on 1–2 OADs. Methods A systematic literature review was conducted to identify randomised controlled trials of GLP-1 RAs in patients inadequately controlled on 1–2 OADs. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA1c), weight, HbA1c target levels (

Previous studies report weight loss to be associated with significantly lower total health care costs among patients with type 2 diabetes mellitus (T2DM). The effect of weight change on health care costs, independent of glycemic control and after controlling for time-varying covariates among T2DM patients, remains unknown.To evaluate the effect of weight change, independent of glycemic control, on all-cause and T2DM-related health care resource utilization (HCRU) and costs among T2DM patients in the United States.A retrospective cohort study was conducted using a linked data extract composed of IQVIA's RWI Data Adjudicated Claims-US and Ambulatory Electronic Medical Record data. Adults (aged ≥ 18 years) with T2DM receiving ≥ 1 oral antidiabetic drug (OAD) medication, glucagon-like peptide-1 receptor agonist (GLP-1RA), and/or short- or long-acting insulin between January 1, 2010, and December 31, 2014 were included (the date of the first observed medical claim with a diagnosis code or medication prescription claim was the index date). Baseline characteristics were evaluated in the 6-month pre-index period. Weight loss (3%, 5%, or 7% from baseline) was evaluated over two 6-month periods (months 1-6 and 7-12) following the index date. Covariates included time-varying weight, hemoglobin A1c (A1c), costs, and HCRU within each 6-month period. Outcomes of interest (all-cause and T2DM-related HCRU and costs) were evaluated in the 6-month (months 13-18) and 12-month (months 13-24) periods following the initial 1- to 6-month and 7- to 12-month post-index periods. Structural nested mean models were used to evaluate the effect of weight change on these outcomes, independent of glycemic control.1,407 patients were included (mean age = 55 years; 55% male), with a mean baseline weight of 102.2 kg (median = 99.7 kg) and a mean baseline A1c of 7.4% (median = 6.9%). In adjusted analysis, weight loss was associated with significantly lower all-cause and T2DM-related annual total health care costs. Compared with those showing no weight change, a 3%, 5%, and 7% weight loss resulted in approximately $500, $800, and $1,100 in savings, respectively, in all-cause annual total health care costs per patient in the year following the weight loss. Similarly, compared with those with no weight change, a 3%, 5%, and 7% weight loss resulted in approximately $200, $300, and $400 in savings, respectively, in T2DM-related annual total health care costs per patient in the following year. Even greater savings (up to ~$2,000 and ~$800 in all-cause and T2DM-related annual costs per patient, respectively) were experienced by those who lost weight compared with those who gained weight.After accounting for glycemic control, this study found that weight loss was associated with additional significant reductions in all-cause and T2DM-related annual total health care costs. Understanding the role of weight loss in T2DM may provide useful evidence for decision makers as they evaluate therapy options for T2DM.This study was funded by Novo Nordisk. Dang-Tan, Smolarz, and Iyer are employees of Novo Nordisk. Karkare and DeKoven (employees of IQVIA) and Fridman (employed by AMF Consulting) were contracted by Novo Nordisk to conduct this study. Fridman also reports personal fees from Shire, GSK, and CSL Behring, outside of the submitted work. Lu, an employee of IQVIA, accessed the database and conducted the statistical analysis for this study.

International audience; Heat shock protein 27 (Hsp27) has an established role in tumor progression and chemo-resistance of castration-resistant prostate cancer (CRPC). Hsp27 protects eukaryotic translation initiation factor 4E (eIF4E) from degradation, thereby maintaining survival during treatment. Phenazine derivative compound #14 was demonstrated to specifically disrupt Hsp27/eIF4E interaction and significantly delay castration-resistant tumor progression in prostate cancer xenografts. In the present work, various strategies of encapsulation of phenazine #14 with either DOTAU (N-[5′-(2′,3′-dioleoyl)uridine]-N′,N′,N′-trimethylammonium tosylate) and DOU-PEG2000 (5′-PEG2000-2′,3′-dioleoyluridine) nucleolipids (NLs) were developed in order to improve its solubilization, biological activity, and bioavailability. We observed that NLs-encapsulated phenazine #14-driven Hsp27-eIF4E interaction disruption increased cytotoxic effects on castration-resistant prostate cancer cell line and inhibited tumor growth in castration-resistant prostate cancer cell xenografted mice compared to phenazine #14 and NLs alone. Phenazine #14 NL encapsulation might represent an interesting nanostrategy for CRPC therapy.

Purpose Patients managing type 2 diabetes mellitus (T2DM) often require combination therapy to meet their blood glucose control targets. With limited real-world evidence focused on the use of glucagon-like peptide 1 receptor agonist (GLP-1RA) therapies, the objective of this study was to describe the association between semaglutide once weekly (OW) initiation and changes in hemoglobin A1c (A1c) levels. Methods This retrospective, descriptive cohort study used the HealthCore Integrated Research Environment (HIRE) to examine commercially insured and Medicare Advantage patients who had T2DM while taking semaglutide OW from December 1, 2017, to April 30, 2019. The first semaglutide OW prescription fill was defined as the study index date. Changes in mean A1c levels and A1c target attainment were evaluated among an intention-to-treat (ITT) population (overall group). Furthermore, a persistent population (PP) analysis on the same outcomes was performed that was limited to ITT patients who were observed to continue to use semaglutide OW at the time of the postindex A1c measurement. In addition, these outcomes were explored in patients stratified based on prior use of GLP-1RA therapy (experienced vs naive) and baseline A1c values >9% (75 mmol/mol). Findings A total of 1888 patients were identified in the overall ITT group. The mean change in the overall ITT group between preindex and postindex A1c values was −0.9% percentage points (−9.8 mmol/mol) (mean preindex A1c, 8.2% [66.1 mmol/mol]) and −1.1 percentage points (−12.0 mmol/mol) (mean preindex A1c, 8.2% [66.1 mmol/mol]) in the PP subgroup (all P 9% (75 mmol/mol), percentage point changes in A1c were −2.2 (−24.0 mmol/mol) and −2.4 (−26.2 mmol/mol) (all P Implications Semaglutide OW is associated with clinically and statistically significant A1C reduction and increases in reaching A1 targets using real-world data, even in GLP-1RA–experienced patients, despite more frequent use of insulin or sodium glucose transport protein 2 inhibitors in this group. Target A1c attainment significantly increased overall and within all subgroups and strata, with approximately half of all patients attaining an A1c value

Introduction This study compared the clinical and economic outcomes of long-term use of liraglutide versus sitagliptin for the treatment of type 2 diabetes (T2DM) in real-world practice in the USA. Methods We identified adult patients (≥ 18 years old) with T2DM who initiated liraglutide or sitagliptin in 2010–2014 using a large claims database. Quarterly glycemic control measures and annual healthcare costs were assessed during the 1st and 2nd years of persistent medication use. Their associations with medication use (liraglutide or sitagliptin) were estimated using multivariable regression models adjusted for patient demographic and clinical characteristics. Results A total of 3113 patients persistently used liraglutide (N = 493) or sitagliptin (N = 2620) for ≥ 1 year [mean age (standard deviation, SD): 53 (8.5) vs. 56 (9.7) years; 48.3% vs. 62.3% males; both p

Introduction The National Health and Nutrition Examination Surveys show that many people with type 2 diabetes (T2D) in the USA fail to achieve recommended treatment targets. In the SUSTAIN 7 randomized controlled trial, once-weekly semaglutide (0.5 and 1.0 mg) was superior to comparative doses of dulaglutide (0.75 and 1.5 mg) in reducing glycated hemoglobin (HbA1c) and body weight in people with T2D. The present study estimated the cost per patient achieving HbA1c treatment targets and weight loss responses with once-weekly semaglutide and dulaglutide in the USA. Methods Numbers needed to treat and annual cost per patient achieving HbA1c targets (including a triple composite endpoint of HbA1c

Background. Chronic obstructive pulmonary disease (COPD) prevalence in Canada has risen over time. COPD-related exacerbations contribute to the increased health care utilization (HCU) in this population. This study investigated the impact of exacerbations on COPD-related HCU. Methods. This retrospective observational cohort study used patient data from the Québec provincial health insurance databases. Eligible patients with a new HCU claim with a diagnostic billing for COPD during 2001–2010 were followed until March 31, 2011. Exacerbation rates and time to first exacerbation were assessed. Unadjusted analyses and multivariable models compared the rate of HCU by exacerbation classification (any [moderate/severe], moderate, or severe). Results. The exacerbation event rate in patients with an exacerbation was 34.3 events/100 patient-years (22.7 for moderate exacerbations and 11.6 for severe exacerbations). Median time to first exacerbation of any classification was 37 months. In unadjusted analyses, COPD-related HCU significantly increased with exacerbation severity. In the multivariable, HCU rates were significantly higher after exacerbation versus before exacerbation (p<0.01) for patients with an exacerbation or moderate exacerbations. For severe exacerbations, general practitioner, respiratory specialist, emergency room, and hospital visits were significantly higher after exacerbation versus before exacerbation (p<0.001). Conclusions. Exacerbations were associated with increased HCU, which was more pronounced for patients with severe exacerbations. Interventions to reduce the risk of exacerbations in patients with COPD may reduce disease burden.

Background: With semaglutide’s FDA approval in Dec 2017, this study sought to provide real-world evidence on its effectiveness in a cohort of early users. Methods: Claims and lab result data from a broad national U.S. CI and MA population were used to identify T2DM patients who initiated semaglutide between 12/1/17 - 6/30/18 (first claim date set as index). Of these, patients who had ≥12-month pre-index health plan eligibility as well as ≥1 HbA1c result within both ≤3 months pre- and ≥3 months post-index were selected. Changes in HbA1c were assessed in all patients, GLP-1 naïve patients and GLP-1 naïve patients with a pre-index HbA1c >9%. Results:Of 107 individuals with T2DM initiating semaglutide, 48.6% were female with median age of 52 years. HbA1c was significantly reduced in all patients (-1.3%), GLP-1 naïve patients (-2.0%) and HbA1c >9% GLP-1 naïve patients (-2.9%) (all p9% GLP-1 naïve) (all p Conclusions: Semaglutide initiation was associated with a significant reduction in HbA1c and increase in HbA1c goal attainment in real-world practice in this preliminary T2DM cohort. Ongoing research will include a broader group of semaglutide users as well as allow for longer post-initiation follow-up to fully assess its effect. Disclosure J. Visaria: Employee; Self; HealthCore. T. Dang-Tan: Employee; Self; Novo Nordisk Inc. P.V. Petraro: Employee; Self; Novo Nordisk Inc. B.K. Nepal: None. V. Willey: Employee; Self; HealthCore. Funding Novo Nordisk

Dhvani Shah,1 Nancy A Risebrough,2 Johnna Perdrizet,1 Neeraj N Iyer,3 Cory Gamble,4 Tam Dang-Tan3 1ICON, Commercialisation and Outcomes, Health Economics, New York, NY, USA; 2ICON, Commercialisation and Outcomes, Health Economics, Toronto, ON, Canada; 3HEOR & Data Analytics, Novo Nordisk Inc, Plainsboro, NJ, USA; 4Medical and Scientific Affairs, Novo Nordisk, Plainsboro, NJ, USA Background: The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcomes Results (LEADER) clinical trial demonstrated that liraglutide added to standard-of-care (SoC) therapy for type 2 diabetes (T2D) with established cardiovascular disease (CVD) or elevated cardiovascular (CV) risk was associated with lower rates of death from CVD, nonfatal myocardial infarction (MI), or nonfatal stroke than SoC alone.Objective: The objective of this study was to assess the cost-effectiveness (CE) and budget impact of liraglutide vs SoC in T2D patients with established CVD or elevated CV risk, over a lifetime horizon from a US managed care perspective.Methods: A cohort state-transition model (costs and benefits discounted at 3% per year) was used to predict diabetes-related complications and death (CV and all-cause). Events, treatment effects, and discontinuation rates were from LEADER trial; utility and cost data (US$, 2017) were from literature. Sensitivity analysis explored the impact of uncertainty on results. Additionally, a budget impact analysis was conducted to evaluate the financial impact of liraglutide use in this population, with displacement from dulaglutide, assuming a health care plan with 1 million members.Results: Liraglutide patients experienced 6.3% fewer events, had event-related cost-savings of $15,182, gained additional life-years of 0.67 and quality-adjusted life-years (QALYs) of 0.57, and had additional total costs ($60,928) vs SoC. Liraglutide was cost-effective with an incremental CE ratio of $106,749/QALY which was below the willingness-to-pay threshold of $150,000/QALY accepted by the Institute of Clinical and Economic Research. Liraglutide was cost-effective across all sensitivity analyses, except when the hazard ratio for all-cause mortality varied. The budget impact was neutral, with a per-plan-per-year and per-member-per-month cost-savings of $266,334 and $0.02, respectively.Conclusion: From a US-managed care perspective, for T2D patients with established CVD or elevated CV risk, liraglutide is a cost-effective and a budget neutral treatment option for health care plans. Keywords: liraglutide, cardiovascular disease, type 2 diabetes, cost-effectiveness, budget impact

Bringing patients with type 2 diabetes to recommended glycated hemoglobin (HbA1c) treatment targets can reduce the risk of developing diabetes-related complications. The aim of the present analysis was to evaluate the short-term cost-effectiveness of once-daily liraglutide 1.8 mg vs once-daily lixisenatide 20 μg as an add-on to metformin for treatment of type 2 diabetes in the US by assessing the cost per patient achieving HbA1c-focused and composite treatment targets.Percentages of patients achieving recommended targets were obtained from the LIRA-LIXI trial, which compared the efficacy and safety of once-daily liraglutide 1.8 mg and once-daily lixisenatide 20 μg as an add-on to metformin in patients with type 2 diabetes failing to achieve glycemic control with metformin. Annual costs were estimated from a healthcare payer perspective. An economic model was developed to evaluate the annual cost per patient achieving target (cost of control) with liraglutide 1.8 mg vs lixisenatide 20 μg for five end-points.Annual treatment costs were higher with liraglutide 1.8 mg than lixisenatide 20 μg, but this was offset by greater clinical efficacy, and the cost of control was lower with liraglutide 1.8 mg than lixisenatide 20 μg for all five end-points. The annual cost of control was USD 3,850, USD 11,404, USD 3,807, USD 4,299, and USD 6,901 lower for liraglutide 1.8 mg than lixisenatide 20 μg for targets of HbA1c 7.0%, HbA1c ≤ 6.5%, HbA1c 7.0% and no weight gain, HbA1c 7.0% with no weight gain and no confirmed hypoglycemia, and HbA1c 7.0% with no weight gain and systolic blood pressure140 mmHg, respectively.Once-daily liraglutide 1.8 mg was associated with greater clinical efficacy than once-daily lixisenatide 20 μg, which resulted in a lower annual cost of control for HbA1c-focused and composite treatment targets.

To describe the healthcare burden associated with not escalating patients with COPD managed with LAMA or LABA monotherapy or LAMA/LABA dual therapy to ICS/LAMA/LABA following a moderate or severe exacerbation. This observational study utilised medical claims from the Quebec Provincial Health Insurance administrative database. Included were patients ≥40 years of age with an incident diagnosis of COPD (during 2002–2011) receiving a respiratory medicine within 2 weeks of a COPD claim and treated with a LAMA, LABA or LAMA/LABA without a preceding moderate or severe exacerbation. Multivariate-adjusted outcomes included incidence density rates for moderate or severe COPD exacerbations and healthcare utilisation, stratified by escalation to ICS/LAMA/LABA triple therapy following an exacerbation. Overall, 19,198 (49.5%) patients experienced COPD exacerbations. Of these, 1,136 (5.9%) were escalated to triple therapy following an exacerbation. Compared with patients switched to triple therapy, those not escalated experienced increased mean incidence density rates (per 100 person-years) for future exacerbations (any: 0.21 vs 0.18, p Failure to escalate to ICS/LAMA/LABA triple therapy following an exacerbation results in increased exacerbations, ER visits and concomitant medication use in patients with COPD. Funded by GSK: HO-13-14097.