Cardiovascular events, mortality, early retirement and costs in >50 000 persons with chronic heart failure in Sweden.

AIMS: We aimed to examine cardiovascular events (stroke and myocardial infarction [MI]), mortality, early retirement and economic costs over 5 years in people with chronic heart failure (CHF) and matched controls in Sweden. METHODS AND RESULTS: Individuals (aged ≥16 years) living in Sweden on 1 January 2012 were identified in an existing database. Individuals with CHF were propensity score matched to controls without CHF by birth year, sex and educational status. We analysed risks of stroke, MI, mortality and early retirement, and compared direct costs (inpatient care, outpatient care and drug costs) and indirect costs (work absence). After matching, there were 53 520 individuals in each cohort. In each cohort, mean age was 69.0 years (standard deviation 8.2), and 29.7% of individuals were women. People with CHF were significantly more likely than controls to experience stroke (hazard ratio 1.46 [95% confidence interval 1.38-1.56]) and MI (1.61 [1.51-1.71]). All-cause mortality was nearly three-fold higher (2.89 [2.80-2.98]) and the likelihood of early retirement was more than three-fold higher (3.69 [3.08-4.42]). Total mean annual costs per person were €9663 (standard error 38) for people with CHF, of which 53% were direct costs, and €2845 (standard error 19) for controls, of which 40% were direct costs. In people with CHF, inpatient costs comprised 78% of total annual mean direct costs over follow-up, outpatient costs contributed 15% and drug costs contributed 8%. In controls, the corresponding proportions were 71%, 18% and 11%. CONCLUSIONS: CHF has a considerable impact on the risk of cardiovascular events and death, early retirement and economic costs. Inpatient admissions and work absence are major contributors to economic costs.

Economic burden of atherosclerotic cardiovascular disease: a matched case-control study in more than 450,000 Swedish individuals.

AIM: To examine direct and indirect costs, early retirement, cardiovascular events and mortality over 5 years in people with atherosclerotic cardiovascular disease (ASCVD) and matched controls in Sweden. METHODS: Individuals aged ≥ 16 years living in Sweden on 01 January 2012 were identified in an existing database. Individuals with ASCVD were propensity score matched to controls without ASCVD by age, sex and educational status. We compared direct healthcare costs (inpatient, outpatient and drug costs), indirect costs (resulting from work absence) and the risk of stroke, myocardial infarction (MI) and early retirement. RESULTS: After matching, there were 231,417 individuals in each cohort. Total mean per-person annual costs were over 2.5 times higher in the ASCVD group versus the controls (€6923 vs €2699). Indirect costs contributed to 60% and 67% of annual costs in the ASCVD and control groups, respectively. Inpatient costs accounted for ≥ 70% of direct healthcare costs. Cumulative total costs over the 5-year period were €32,011 in the ASCVD group and €12,931 in the controls. People with ASCVD were 3 times more likely to enter early retirement than controls (hazard ratio [HR] 3.02 [95% CI 2.76-3.31]) and approximately 2 times more likely to experience stroke (HR 1.83 [1.77-1.89]) or MI (HR 2.27 [2.20-2.34]). CONCLUSION: ASCVD is associated with both economic and clinical impacts. People with ASCVD incurred considerably higher costs than matched controls, with indirect costs resulting from work absence and inpatient admissions being major cost drivers, and were also more likely to experience additional ASCVD events.

Atherosclerotic Cardiovascular Disease in Type 2 Diabetes: A Retrospective, Observational Study of Economic and Clinical Burden in Sweden.

INTRODUCTION: Individuals with type 2 diabetes (T2D) are at high risk of experiencing atherosclerotic cardiovascular disease (ASCVD), which is associated with morbidity, mortality and healthcare resource utilisation. Clinical guidelines recommend the use of glucose-lowering medications with cardiovascular benefits in individuals with T2D and cardiovascular disease, but there is evidence that this is not reflected in clinical practice. We used linked national registry data from Sweden to compare outcomes in people with T2D and ASCVD against matched controls with T2D without ASCVD, over 5 years. Direct costs (inpatient, outpatient and selected drug costs), indirect costs resulting from work absence, early retirement, cardiovascular events and mortality were examined. METHODS: Individuals with T2D who were at least 16 years old and were alive and resident in Sweden on 1 January 2012 were identified in an existing database. In four separate analyses, individuals with a record indicating ASCVD according to a broad definition, peripheral artery disease (PAD), stroke or myocardial infarction (MI) before 1 January 2012 were identified using diagnosis and/or procedure codes and propensity score matched 1:1 to controls with T2D and without ASCVD, using covariates for birth, sex and level of education in 2012. Follow-up continued until death, migration from Sweden or the end of the study period in 2016. RESULTS: In total, 80,305 individuals with ASCVD, 15,397 individuals with PAD, 17,539 individuals with previous stroke and 25,729 individuals with previous MI were included. Total mean annual costs per person were €14,785 for PAD (2.7 × costs for controls), €11,397 for previous stroke (2.2 × controls), €10,730 for ASCVD (1.9 × controls) and €10,342 for previous MI (1.7 × controls). Indirect costs and costs of inpatient care were the major cost drivers. ASCVD, PAD, stroke and MI were all associated with an increased likelihood of early retirement, cardiovascular events and mortality. CONCLUSIONS: ASCVD is associated with considerable costs, morbidity and mortality in individuals with T2D. These results support structured assessment of ASCVD risk and broader implementation of guideline-recommended treatments in T2D healthcare.

Nationwide cardiovascular risk categorization: applying the European Society of Cardiology guidelines to the Swedish National Diabetes Register.

AIMS: The 2021 European Society of Cardiology (ESC) guidelines recommend that patients with type 2 diabetes (T2D) with a very high cardiovascular disease (CVD) risk receive cardiovascular (CV)-protective glucose-lowering medication (glucagon-like peptide-1 receptor agonists or sodium-glucose co-transporter-2 inhibitors). This analysis compared previous prescribing practices with the ESC recommendations. METHODS AND RESULTS: Patients in the Swedish National Diabetes Register (NDR) with T2D, aged 18-90 years, not receiving CV-protective glucose-lowering medication in 2017 were identified, and the ESC criteria for very high CVD risk were applied. The composite outcome of major adverse CV events (MACEs; defined as CV death, non-fatal stroke or non-fatal myocardial infarction) during 2017 was calculated, and the number of MACE avoided with semaglutide, an example of a CV-protective glucose-lowering medication, was estimated for patients with a certain CV risk score. Of the 320 028 patients in the NDR with T2D who were not receiving CV-protective glucose-lowering medication, 129 512 patients had a very high CVD risk. Patients with a very high CVD risk had a high incidence of MACE (75.4 events/1000 person-years), which was higher in those with atherosclerotic CVD (ASCVD) with and without elevated glycated haemoglobin (>9%; 136.5 and 90.8 events/1000 person-years, respectively). If patients with a very high CVD risk, according to the ESC, and ASCVD received semaglutide, 803 MACE may have been avoided in 2017. CONCLUSIONS: This analysis highlights differences between previous prescribing practices in Sweden and the 2021 ESC guidelines and offers strategies to prioritize CV-protective glucose-lowering medication for patients who would benefit most.

Type 2 diabetes, or T2D, causes blood sugar levels to get too high. Nearly one-third of people with T2D also have diseases of the heart and blood vessels, such as heart attacks and strokes. These are known as cardiovascular diseases or events. Some T2D medications can also lower the risk of cardiovascular disease. Using data from national healthcare registries, we looked at how many people with T2D in Sweden had a very high cardiovascular disease risk. Healthcare systems often have limited budgets and may not treat all people with a very high cardiovascular disease risk. So, we looked at ways to identify which patients with T2D would benefit most from treatment. We also estimated how many cardiovascular events may be prevented by giving these patients cardiovascular risk-lowering T2D medication, using a medication called semaglutide as an example.The registry included 348 857 people with T2D, and 91.7% (320 028) were not given cardiovascular risk-lowering T2D medications. Of the people not given medications, 40.5% (129 512) had a very high cardiovascular disease risk. On average, we found that people with a very high cardiovascular disease risk and previous cardiovascular events ended up having more cardiovascular events than those without previous events. People who also regularly had high average blood sugar levels, measured using a marker in the blood called glycated haemoglobin, or HbA1c, had even more cardiovascular events.Giving semaglutide to people with a very high cardiovascular disease risk who have already had a cardiovascular event may prevent around 803 cardiovascular events each year.

Insights into the early use of oral semaglutide in routine clinical practice: The IGNITE study.

Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and showed significant benefits in glycaemic control and weight reduction versus active comparators in the PIONEER phase 3a randomized controlled trial programme. In this retrospective study, we present early data on the use of oral semaglutide in clinical practice, from the US IBM Explorys electronic health record database. In 782 patients prescribed oral semaglutide, 54.5% were women, and the mean age (SD) was 57.8 years (11.3); 66.0% of patients received their prescription from a primary care practitioner. Although prescribing information recommends increasing the dose to 7 mg after 30 days, 37.0% of patients received a prescription only for the initial 3 mg dose. Mean body mass index was 36.2 kg/m2 (7.6); mean HbA1c was 8.4% (1.8%). Mean HbA1c change from baseline to approximately 6 months after oral semaglutide initiation was -0.9% (95% CI: -1.1%; -0.6%), with greater reductions in patients with higher baseline HbA1c. These data indicate prevalent early adoption of oral semaglutide in primary care, show real-world improvements in glycaemic control, and identify potential treatment gaps.

Switching "Real-World" Diabetes Patients to Degludec from Other Basal Insulins Provides Different Clinical Benefits According to Their Baseline Glycemic Control.

INTRODUCTION: The stable, ultra-long duration of action of insulin degludec (degludec) minimizes fluctuations in glucose-lowering activity over the daily (24-h) dosing period, and comparative studies with other basal insulins suggest that these properties translate into a lower risk of hypoglycemia at equivalent levels of glycemic control. Results from the real-world European multicenter, retrospective chart review study of 2550 patients with type 1 and type 2 diabetes (T1D and T2D) in routine clinical care EU-TREAT (NCT02662114) showed that patients benefited from improved glycemic control and significantly reduced rates of hypoglycemia following a switch to degludec. METHODS: In this post hoc analysis, EU-TREAT patients were stratified into good (≤ 7.5% HbA1c), intermediate (> 7.5 to ≤ 8.5% HbA1c), and poor (> 8.5% HbA1c) glycemic control at baseline to investigate the possibility of differential benefits, either improved control or reduced risk of hypoglycemia, whichever the need. Changes in HbA1c, overall hypoglycemia, and total insulin dose from baseline to 6 and 12 months follow-up were assessed for each group. RESULTS: For both T1D and T2D patients, those in good initial control experienced significant reductions in rates of hypoglycemia and total insulin dose following the switch, without compromising control. Those in poor initial control achieved significant improvements in HbA1c with no change in rates of hypoglycemia or total insulin dose. CONCLUSION: This analysis expands the findings of EU-TREAT by showing differential changes in the clinical endpoints depending on particular need. It introduces the possibility that the differential benefits of degludec could address two of the renowned clinical challenges faced when treating diabetes: improving glycemic control for optimal management of T1D and titrating insulin dose in T2D, both without fear of increased hypoglycemia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02662114. FUNDING: Novo Nordisk A/S.

Improved Glycemic Control Achieved by Switching to Insulin Degludec in Insulin-Treated Patients with Type 2 Diabetes in a Real-World Setting: a Non-interventional, Retrospective Cohort Study.

INTRODUCTION: Retrospective cohort study evaluating the clinical effectiveness of insulin degludec (IDeg) in insulin-treated patients with type 2 diabetes switching from other insulins to IDeg in a real-world setting. METHODS: Data were drawn from the Maccabi Health Management Organization in Israel and included patients treated with IDeg between 1 September 2014 and 29 February 2016. Main inclusion criteria were age ≥18 years, diagnosis of type 2 diabetes, and treated with insulin for at least 1 year prior to IDeg initiation. HbA1c, insulin dose, body weight, and body mass index were recorded before and 90 and 180 days post-switch. RESULTS: Of 211 eligible patients, 57% were male, mean age ± SD 62.2 ± 12.1 years, and diabetes duration >10 years. Switching to IDeg decreased HbA1c from a mean 8.8 ± 1.5% (73.0 ± 16.4 mmol/mol) baseline by 0.58 ± 1.0% (6.3 ± 10.9 mmol/mol) (p < 0.001). Baseline HbA1c of >8.5% (69.0 mmol/mol) and daily insulin dose of ≥50 U were associated with a greater reduction in HbA1c [1.0 ± 1.1% (10.9 ± 12.0 mmol/mol) and 1.2 ± 1.1% (13.1 ± 12.0 mmol/mol), respectively] compared with the total population. At 180 days post-switch, the mean daily basal insulin dose increased by 2 U compared with pre-switch. There was no significant change in body weight post-switch. CONCLUSIONS: In a real-world setting, switching from another insulin to IDeg significantly improved glycemic control in patients with type 2 diabetes, without significant weight gain and with only a modest increase in insulin dose after IDeg initiation. FUNDING: Novo Nordisk.

Insulin Degludec in Clinical Practice: A Review of Japanese Real-World Data.

INTRODUCTION: In this literature review we evaluated the real-world clinical effectiveness of switching Japanese diabetic patients from their current insulin regimen to insulin degludec (IDeg). METHODS: Studies were identified from Japanese Diabetes Society (JDS) abstracts (2014-2015) and PubMed (2012 onwards). Inclusion criteria were: Japanese population, >15 participants, and studies switching patients from basal or basal-bolus insulin regimens to IDeg. Randomized controlled trials and case reports were excluded. Weighted mean changes in safety and effectiveness endpoints were calculated using the number of patients in each study. RESULTS: In total, 81 JDS abstracts and seven manuscripts met the search criteria, representing 4238 patients [1028 with type 1 diabetes (T1D), 602 with type 2 diabetes (T2D), 2608 with unspecified or mixed diabetes]. Glycated hemoglobin (HbA1c) was reported in 93% of studies, with an improvement in 84% of these (51% significant, 33% numerical), no change in 12%, and worsening in 4% (3% numerical, 1% significant). Across all studies, the weighted mean absolute change in HbA1c was -0.3% (-2.7 mmol/mol). Basal insulin dose was reported in 58% of studies and was lower in 60% of these (30% significant, 30% numerical), numerically unchanged in 26%, and higher in 14% (2% significant, 12% numerical). The weighted mean change in basal insulin dose was -4.8% and -3.0% for all studies and for studies with only significant results, respectively. The weighted mean change in basal dose based on all studies was -8.9, -5.5, and -2.9% for the T1D, T2D, and unspecified patient populations, respectively. Hypoglycemia was recorded in 31% of the studies. After switching treatment to IDeg, 55% of studies reported decreased hypoglycemia, 29% no change, and 16% an increase. Quality of life (QoL) was measured in 11% of studies, of which 82% reported improved QoL after switching, and 18% reported no change in QoL. CONCLUSION: Switching from a conventional basal insulin to IDeg has the potential to improve HbA1c with a lower insulin dose. Switching to IDeg may also provide a reduced risk of hypoglycemia and improvement in QoL. FUNDING: Novo Nordisk.

The Association Between Body Mass Index and Health and Economic Outcomes in the United States.

OBJECTIVE: The objective of this study is to provide current estimates of the association between obesity and health outcomes and to examine these associations among subgroups of interest (pre-diabetes, type 2 diabetes [T2D], and neither pre-diabetes nor T2D) in the United States. METHODS: Data were analyzed from the 2013 US National Health and Wellness Survey (N = 71,530). Respondents were categorized by body mass index (BMI) class (normal, overweight, obese class I, obese class II, obese class III). RESULTS: As BMI increased, health status decreased significantly (and to a clinically relevant degree) for respondents categorized as obese compared with normal weight. Work productivity impairment, physician visits, emergency room visits, and costs also increased significantly as BMI increased. The pattern of results was similar across the three subgroups. CONCLUSIONS: Increasing BMI was associated with decreasing health status and increasing work-related impairment, healthcare resource utilization, and costs.

Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study.

OBJECTIVE: Hypoglycemia has been associated with an increased risk of cardiovascular (CV) events and all-cause mortality. This study assessed whether, in a nationally representative population, there is an association between hypoglycemia, the risk of CV events, and all-cause mortality among insulin-treated people with type 1 diabetes or type 2 diabetes. RESEARCH DESIGN AND METHODS: This retrospective cohort study used data from the Clinical Practice Research Datalink database and included all insulin-treated patients (≥30 years of age) with a diagnosis of diabetes. RESULTS: In patients who experienced hypoglycemia, hazard ratios (HRs) for CV events in people with type 1 diabetes were 1.51 (95% CI 0.83, 2.75; P = ns) and 1.61 (1.17, 2.22), respectively, for those with and without a history of CV disease (CVD) before the index date. In people with type 2 diabetes, the HRs for patients with and without a history of CVD were 1.60 (1.21, 2.12) and 1.49 (1.23, 1.82), respectively. For all-cause mortality, HRs in people with type 1 diabetes were 1.98 (1.25, 3.17), and 2.03 (1.66, 2.47), respectively, for those with and without a history of CVD. Among people with type 2 diabetes, HRs were 1.74 (1.39, 2.18) and 2.48 (2.21, 2.79), respectively, for those with and without a history of CVD. The median time (interquartile range) from first hypoglycemia event to first CV event was 1.5 years (0.5, 3.5 years) and 1.5 years (0.5, 3.0 years), respectively, for people with type 1 and type 2 diabetes. CONCLUSIONS: Hypoglycemia is associated with an increased risk of CV events and all-cause mortality in insulin-treated patients with diabetes. The relationship between hypoglycemia and CV outcomes and mortality exists over a long period.

Frequency of blood glucose testing among insulin-treated diabetes mellitus patients in the United Kingdom.

BACKGROUND: Through a retrospective database analysis, this study seeks to provide an understanding of the utilization of SMBG by insulin therapy and diabetes type and to estimate healthcare costs of blood glucose monitoring in the UK diabetes population. METHODS: Data were obtained from the IMS LifeLink Electronic Medical Record-Europe (EMR-EU) Database, a longitudinal database containing anonymized patient records from physician-practice data systems of office-based physicians in the UK. Depending on the insulin types used for type 1 and type 2 diabetes, patients were sub-categorized into one of four insulin regimen groups (basal, bolus, pre-mixed, or basal-bolus). Frequency of blood glucose testing was assessed descriptively throughout the 12-month post-index period, and generalized linear models were used to evaluate the effect of baseline characteristics, including insulin type, on the likelihood of blood glucose test utilization. Healthcare resource utilization and costs for all-cause services were assessed by insulin type. RESULTS: This study identified 8322 type 1 and type 2 diabetes patients with two insulin pharmacy records between January 1, 2009 and December 31, 2010. After applying study inclusion and exclusion criteria, a total of 2676 (32.2%) insulin-treated diabetes mellitus patients in the UK were identified, with the number of pharmacy blood glucose test strips averaging 771.1 (median 600). The glucose testing frequency was lowest among basal-only insulin patients and pre-mixed insulin patients (mean=576.2 [median=450] and mean=599.5 [median=500], respectively; non-significantly different) compared to other insulin types. CONCLUSION: Although the data did not capture the glucose frequency comprehensively, it varied significantly by insulin types, and was higher than what is recommended in the guidelines for patients with type 2 diabetes.

Cost of Self-Monitoring of Blood Glucose in Canada among Patients on an Insulin Regimen for Diabetes.

INTRODUCTION: People with diabetes are at a higher risk of developing a variety of medical conditions relative to those without diabetes, resulting in increased healthcare costs. Self-monitoring of blood glucose (SMBG) is accepted as a recommended element of effective diabetes self-management. However, little is known about the real-world frequency and actual expenditures associated with SMBG, as well as the impact of SMBG costs relative to the cost of diabetes treatments. The primary objective is to evaluate the real-world utilization and costs of SMBG tests in Canada among insulin-treated diabetes patients during a 12-month follow-up period. METHODS: A retrospective cohort study was conducted using the IMS Brogan Inc. Drug Plan database from July 1, 2006 through June 30, 2010. Total costs during the 12-month follow-up period were assessed, focusing on blood glucose (BG) testing strip costs, insulin therapy costs, and costs associated with oral antidiabetics medications. All prevalent patients with two or more prescriptions for insulin between January 1, 2007 and December 31, 2009 were initially included in the analysis, the first prescription serving as their index date. Depending on the insulin type(s) used, patients were subcategorized into one of four insulin regimen groups (basal, bolus, premix, or basal-bolus). RESULTS: Among an initial sample of patients with two or more claims for insulin between January 1, 2007 and December 31, 2009, 142,551 met the aforementioned inclusion and exclusion criteria. An overall mean utilization of pharmacy-based blood glucose testing of approximately 1,094 strips per person per year was observed, with an average cost per testing strip of Canadian $0.79. SMBG treatment costs for insulin users ($860), specifically those associated with prescription testing strips, totaled 41.6% of the average annual pharmacy costs of diabetes-related prescriptions ($2,068). CONCLUSION: This study shows that SMBG accounts for approximately 40% of the total diabetes-related pharmacy costs for insulin users.