Direct and indirect costs of heart failure in relation to diabetes status - A nationwide study.

BACKGROUND AND AIM: Heart failure (HF) and diabetes mellitus (DM) are burdensome chronic diseases with high lifetime risks and numerous studies indicate associations between HF and DM. The objective of this study was to investigate the direct and indirect costs of HF patients with and without DM. METHODS AND RESULTS: Patients with a first-time diagnosis of HF from 1998 to 2016 were identified through nationwide Danish registries and stratified according to DM status into HF with or without DM. The economic healthcare cost analysis was based on both direct costs, including hospitalization, procedures, medication and indirect costs including social welfare and lost productivity. The economic burden was investigated prior to, at, and following diagnosis of HF. Patients with concomitant HF and DM were younger (median age 74 vs. 77), had more comorbidities and fewer were female as compared to patients with HF but without DM. The socioeconomic burden of concomitant HF and DM compared to HF alone was substantially higher; 45% in direct costs (€16,237 vs. €11,184), 35% in home care costs (€3123 vs. €2320), 8% in social transfer income (€17,257 vs. €15,994) and they had 27% lower income (€10,136 vs. €13,845). The economic burden peaked at year of diagnosis, but the difference became increasingly pronounced in the years following the HF diagnosis. CONCLUSION: Patients with concomitant HF and DM had a significantly higher economic burden compared to patients with HF but without DM.

Epidemiology and economic burden of amyotrophic lateral sclerosis in the United States: a literature review.

Objective: This review sought to gain a comprehensive, up-to-date understanding of the epidemiology and cost and healthcare resource use (HCRU) burden of amyotrophic lateral sclerosis (ALS) in the US, at a patient and national level. Methods: A targeted literature review (TLR) to identify epidemiological evidence (prevalence, incidence, mortality, survival), and systematic literature review (SLR) to identify cost and HCRU data published since January 2016, were performed. MEDLINE databases and Embase searches were conducted in January 2021. Key congresses (2019-2020) and bibliographies of relevant SLRs were hand-searched. Two high-quality SLRs were reviewed for additional cost data published between January 2001-2015. Registry and database studies were prioritized for epidemiological evidence. To allow comparison between studies in this publication, only evidence from the US was considered, with costs inflated to the 2020/2021 cost-year and converted to US dollars. Results: Eight studies from the epidemiology TLR, and eighteen from the cost and HCRU SLR, were extracted. Reported ALS incidence in the US was ∼1.5 per 100,000 person-years, and point prevalence ranged from 3.84-5.56 per 100,000 population. Total US national costs spanned ∼$212 million-∼$1.4 billion USD/year, and variably consisted of direct costs associated with HCRU and indirect costs. Conclusions: The national cost of ∼$1.02 billion USD/year (estimated using a prevalence of 16,055 cases) best aligns with prevalence estimates found in the TLR (equating to ∼13,000-18,000 cases). However, large-scale, population-based studies are necessary to precisely assess US epidemiology of ALS and capture all costs needed to inform cost-effectiveness models and resource planning.

Characteristics of newly diagnosed adults with type 1 diabetes in the UK and evolution of glycaemic control, body mass index and Charlson comorbidity index over the first 5 years after diagnosis.

AIMS: This retrospective, longitudinal study characterised 2430 adults (mean age 40.8±16.1years) with newly diagnosed type 1 diabetes (T1D) over the first 5years of insulin treatment. METHODS: Data from 1year pre- and up to 5 years post-insulin initiation were extracted from the UK Clinical Practice Research Datalink (1990-2013). Baseline HbA1c, BMI and Charlson comorbidity index (CCI) score were compared with data at 1, 2, 3 and 5 years. RESULTS: Mean HbA1c decreased significantly from baseline 95±32.8mmol/mol (10.8±3.0%) to 61±21.9mmol/mol (7.7±2.0%) at 1year, remaining significantly lower at 2, 3 and 5 years (p<0.0001). One year after initiating insulin, only 6.3% of patients had HbA1c <48mmol/mol (<6.5%). There was no further improvement in HbA1c after 1year. Mean BMI increased significantly from baseline 25.3±5.5kg/m2 to 27.2±5.8kg/m2 at 1year; p<0.0001), remaining significantly higher thereafter, with over two-thirds having overweight/obesity by year 5. Mean CCI score increased significantly (1.32, baseline; 1.46, year 1; 1.75, year 5). CCI patterns were similar within BMI and HbA1c strata. CONCLUSIONS: More intensive support to reach and maintain glycaemic targets soon post-diagnosis, while avoiding weight gain, and prevention and optimal management of comorbidities are warranted.

The economic burden of heart failure in Denmark from 1998 to 2016.

BACKGROUND: Heart failure (HF) imposes a large burden on both the individual and the society. The aim of this study was to investigate the economic burden (either direct or indirect costs) attributed to patients with HF before, at, and after time of diagnosis. METHODS AND RESULTS: Using Danish nationwide registries we identified all patients > 18 years with a first-time diagnosis of HF from 1998-2016 and matched them 1:1 with a control group from the background population on age, gender, marital status, and educational level. The economic analysis of the total costs after diagnosis was based on direct costs including hospitalization, procedures, medication, and indirect costs including social welfare and lost productivity to estimate the annual cost of HF. A total of 176 067 HF patients with a median age of 76 (interquartile range 67-84) years and 55% male were included. Patients with HF incurred an average of €17 039 in total annual direct (€11 926) and indirect (€5113) healthcare costs peaking at year of diagnosis compared to €5936 in the control group with the majority attributable to inpatient admissions. The total annual net costs including public transfer after index HF were €11 957 higher in patients with HF compared to controls and the economic consequences were evident more than 2 years prior to the diagnosis of HF. CONCLUSION: Patients with HF impose significantly higher total annual healthcare costs compared to a matched control group with findings evident more than 2 years prior to HF diagnosis.

Liraglutide Versus SGLT-2 Inhibitors in People with Type 2 Diabetes: A Network Meta-Analysis.

INTRODUCTION: For people with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs (OADs), evidence from both randomized controlled trials (RCTs) and real-world studies has demonstrated that treatment intensification with liraglutide offers effective glycemic control, weight reduction, and a lower risk of hypoglycemia compared to treatment intensification with insulin or additional OADs. Sodium glucose cotransporter 2 (SGLT-2) inhibitors are a new class of OADs that have also been shown to be effective in T2DM patients inadequately controlled with OADs. Currently there are no head-to-head RCTs comparing these to liraglutide. METHODS: We aimed to evaluate the relative efficacy, using network meta-analysis (NMA), of treatment intensification with liraglutide and SGLT-2 inhibitors people with T2DM who have been treated with metformin (alone or in combination with SU, DPP-4, and TZD). We performed a systematic literature review to identify relevant RCTs comparing liraglutide (1.2 and 1.8 mg), canagliflozin (100 and 300 mg), empagliflozin (10 and 25 mg), or dapagliflozin (5 and 10 mg) to placebo. To strengthen the indirect evidence base, we also included non-placebo RCTs where sitagliptin (100 mg) was the active comparator. Bayesian NMA was performed on the following outcomes to assess the relative efficacy and safety of interventions: reduction (change) in HbA1c, weight, and fasting plasma glucose (FPG) as well as proportion reaching target HbA1c (<7%), and risk of hypoglycemia. Doses for each intervention were considered separately. RESULTS: A total of 16 RCTs were identified. All trials were similar with respect to important baseline characteristics and study design. Both doses of liraglutide were generally statistically significantly superior to the SGLT-2s with respect to change from baseline in HbA1c and FPG as well as odds of reaching target HbA1c <7%. For weight, canagliflozin 300 mg was superior to liraglutide 1.2 mg, and SGLT-2s were generally associated with larger change from baseline in weight. For risk of major or minor hypoglycemia, no differences were found between treatments. CONCLUSIONS: Compared to SGLT-2 inhibitors, liraglutide offers improvement in HbA1c and FPG. Reductions in weight are likely comparable between liraglutide and SGLT-2s. Liraglutide did not differ from SGLT-2s in terms of risk of hypoglycemia. Given the lack of head-to-head evidence, this analysis provides valuable insight into the comparative outcomes of liraglutide versus SGLT-2 inhibitors.

Clinical Effectiveness of Liraglutide vs Sitagliptin on Glycemic Control and Body Weight in Patients with Type 2 Diabetes: A Retrospective Assessment in Sweden.

INTRODUCTION: The aim of the present study was to use real-world data from Swedish primary-care and national registries to understand clinical outcomes in patients with Type 2 diabetes (T2D) treated with liraglutide in clinical practice, and to compare with data from those treated with sitagliptin. METHODS: This was a non-interventional, retrospective study conducted between February 2014 and September 2014 using T2D patient data from Swedish primary-care centers and national healthcare registries. The primary objective was to assess the effectiveness of liraglutide in control of glycemia and body weight in clinical practice (stage 1). The secondary objective was to compare the clinical effectiveness of liraglutide with sitagliptin on glycemic control and body weight in clinical practice in a propensity-score-matched population (stage 2). RESULTS: In stage 1 (n = 402), 39.4% of patients treated with liraglutide achieved ≥1.0% (10.9 mmol/mol) reduction in glycated hemoglobin (HbA1c) after 180 days of treatment and 54.9% achieved the target HbA1c of <7.0% (53.0 mmol/mol). Moreover, compared with baseline, 22.5% of patients treated with liraglutide achieved both ≥1.0% reduction in HbA1c and ≥3.0% reduction in body weight. In stage 2, a significantly greater proportion of patients receiving liraglutide (n = 180) than sitagliptin (n = 208) achieved ≥1.0% reduction in HbA1c [52.9% vs 33.5%, respectively (P = 0.0002)]. Mean body-weight loss was also significantly greater in patients receiving liraglutide vs sitagliptin [-3.5 vs -1.3 kg, respectively (P < 0.0001)]. CONCLUSION: This study provides real-world evidence from Sweden corroborating previous clinical trials that demonstrate greater efficacy of liraglutide over sitagliptin on glycemic control and body-weight reduction in patients with T2D. FUNDING: Novo Nordisk A/S. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02077946.

Evaluating the Cost of Bringing People with Type 2 Diabetes Mellitus to Multiple Targets of Treatment in Canada.

PURPOSE: Evidence suggests that clinical outcomes for people with type 2 diabetes mellitus can be improved through multifactorial treatment. The key challenges in the successful treatment of type 2 diabetes include maintaining tight glycemic control, minimizing the risk of hypoglycemia, controlling cardiovascular risk factors, and reducing or controlling weight. The aim of the present analysis was to evaluate the cost per patient achieving a composite clinical end point (glycosylated hemoglobin <7%, with no weight gain and no hypoglycemic events) in patients with type 2 diabetes in Quebec, Quebec, Canada, receiving liraglutide 1.2 mg, liraglutide 1.8 mg, thiazolidinedione, sulfonylurea, insulin glargine, sitagliptin, or exenatide. METHODS: The proportion of patients achieving control was taken from a meta-analysis that was based on the Phase III trial program of liraglutide. Treatment costs, estimated from a health care payer perspective, were calculated on the basis of the trials included in the meta-analysis and captured the study drug, needles, self-monitoring of blood glucose (SMBG) test strips, SMBG lancets, and other antidiabetes medications received. Cost-effectiveness in terms of cost per patient achieving the composite end point (cost of control) was evaluated with an economic model developed in Microsoft Excel. No discounting was applied to cost or clinical outcomes because these were not projected beyond a 1-year time horizon. Sensitivity analyses were performed. FINDINGS: Liraglutide 1.8 mg was associated with the lowest number needed to treat, with 3 patients needing to be treated to bring 1 patient to the composite end point. Pioglitazone was associated with the highest number needed to treat, with 17 patients requiring treatment to bring 1 patient to the composite end point. Evaluation of only annual pharmacy costs indicated that liraglutide 1.8 mg was the most costly treatment at Can$2780 per patient per year. Pioglitazone and glimepiride were associated with the lowest direct annual costs. Combining the clinical efficacy data with the annual cost of medications produced cost of control values of Can$6070 (liraglutide 1.2 mg), Can$6949 (liraglutide 1.8 mg), Can$7237 (glimepiride), Can$7704 (exenatide), Can$8297 (insulin glargine), Can$8741 (pioglitazone), and Can$9270 (sitagliptin) per patient achieving the composite end point. IMPLICATIONS: Liraglutide 1.2 mg and 1.8 mg were associated with the lowest cost of control values, driven by the high proportion of patients achieving the composite end point, which offset the higher medication costs. A relatively low cost of control value was achieved for glimepiride, driven by low acquisition costs, despite relatively few patients achieving the composite end point.

Investigating the Evidence of the Real-Life Impact of Acute Hyperglycaemia.

UNLABELLED: Poorly controlled diabetes mellitus (DM) is associated with the development of long-term micro- and macro-vascular complications. The predominant focus of anti-diabetic therapy has been on lowering glycosylated haemoglobin levels, with a strong emphasis on fasting plasma glucose (particularly in Type 2 DM). There is considerable evidence indicating that post-meal hyperglycaemic levels are independently associated with higher risks of macro-vascular disease. Although some have identified mechanisms which may account for these observations, interventions which have specifically targeted postprandial glucose rises showed little or no effect in reducing cardiovascular risk. Clinical experience and some recent studies suggest acute hyperglycaemia affects cognition and other indicators of performance, equivalent to impairment seen during hypoglycaemia. In this brief report, we evaluated the published studies and argue that acute hyperglycaemia is worth investigating in relation to the real-life implications. In summary, evidence exists suggesting that acute hyperglycaemia may lead to impaired cognitive performance and productivity, but the relationship between these effects and daily activities remains poorly understood. Further research is required to enhance our understanding of acute hyperglycaemia in daily life. A better appreciation of clinically relevant effects of acute hyperglycaemia will allow us to determine whether it needs to be addressed by specific treatment. FUNDING: Novo Nordisk A/S Søborg, Denmark.

Willingness to pay for improvements in chronic long-acting insulin therapy in individuals with type 1 or type 2 diabetes mellitus.

BACKGROUND: Long-acting insulin treatments with varying clinical benefits are currently available for patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). The current evidence base demonstrates the efficacy of treatments, but it is critical also to understand patient preferences regarding treatments and how they are determined. OBJECTIVE: This study aimed to measure the willingness to pay (WTP) of individuals with diabetes in the United Kingdom for different attributes of long-acting insulin therapy. METHODS: A survey based on discrete choice experiment methodology was developed to elicit the preferences and values of adults with T1DM or insulin-dependent T2DM regarding different aspects of their therapy. Participants were presented with a series of 27 paired choices and asked which they preferred. WTP values were calculated for relevant attribute levels. RESULTS: A total of 252 participants completed the questionnaire (52% response rate); 143 had T1DM and 109 had insulin-treated T2DM. The highest WTP values in participants with T1DM were avoiding 2-kg or 4-kg weight gain (£29 and £58, respectively), avoiding major difficulties with the injection device (£49), increasing the number of days per week when blood glucose levels are in the target range from 2 to 6 (£40), reducing the number of daily injections from 3 to 1 (£39), and avoiding nighttime hypoglycemia (£33). In participants with T2DM, similar factors had the highest WTP. CONCLUSIONS: This is the first study to assess WTP for long-acting insulin therapy and could have implications for future guidelines on diabetes management, however some limitations, notably in sample selection, could affect generalizability of the results. In both T1DM and T2DM, the highest WTP values were for avoidance of weight gain, and reduction in the number of injections and hypoglycemia.

Impact of obesity and type 2 diabetes on health-related quality of life in the general population in England.

BACKGROUND: Weight gain can contribute towards the development of type 2 diabetes (T2D), and some treatments for T2D can lead to weight gain. The aim of this study was to determine whether having T2D and also being obese had a greater or lesser impact on health-related quality of life (HRQoL) than having either of the two conditions alone. METHODS: The 2003 dataset of the Health Survey for England (HSE) was analyzed using multiple regression analyses to examine the influence of obesity and T2D on HRQoL, and to determine whether there was any interaction between these two disutilities. RESULTS: T2D reduced HRQoL by 0.029 points, and obesity reduced HRQoL by 0.027 points. There was no significant interaction effect between T2D and obesity, suggesting that the effect of having both T2D and being obese is simply additive and results in a reduction in HRQoL of 0.056. CONCLUSIONS: Based on analysis of HSE 2003 data, people with either T2D or obesity experience significant reduction in HRQoL and people with both conditions have a reduction in HRQoL equal to the sum of the two independent effects. The effect of obesity on HRQoL in people with T2D should be considered when selecting a therapy.