Evaluating the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) for type 2 diabetes in Spain based on real-world clinical evidence.

AIM: To evaluate the long-term cost-effectiveness of fixed-ratio combination insulin degludec/liraglutide (IDegLira) versus comparator regimens for type 2 diabetes in Spain, based on real-world evidence. MATERIALS AND METHODS: Clinical data were taken from the European Xultophy Treatment Retrospective Audit (EXTRA) real-world evidence study in which patients failing to meet glycaemic targets were switched to IDegLira. Baseline regimens (prior to IDegLira treatment) were categorized as: multiple daily insulin injections (MDI; 28%); glucagon-like peptide-1 (GLP-1) receptor agonists in combination with insulin (24%); basal insulin (19%); GLP-1 receptor agonists (10%); and non-injectable medications (19%). The IQVIA CORE Diabetes Model was used to project long-term outcomes for patients switching to IDegLira or continuing their baseline regimens (excluding non-injectable regimens). Costs were accounted from a Spanish National Health System perspective. Future costs and clinical benefits were discounted at 3% annually and sensitivity analyses were performed. RESULTS: IDegLira was projected to reduce the incidence of diabetes-related complications and improve quality-adjusted life expectancy versus all four comparators. IDegLira reduced direct medical costs versus GLP-1 receptor agonists in combination with insulin, and versus GLP-1 receptor agonist therapy, and was therefore considered dominant (cost saving while improving outcomes). IDegLira was found to be cost-effective versus MDI and basal insulin with incremental cost-effectiveness ratios of EUR 3013 per quality-adjusted life-year (QALY) gained and EUR 6890 per QALY gained, respectively. CONCLUSIONS: Long-term projections based on real-world evidence indicated that IDegLira is likely to improve clinical outcomes and reduce costs or be cost-effective compared with other injectable regimens in people with type 2 diabetes in Spain.

Slow Titration and Delayed Intensification of Basal Insulin Among Patients with Type 2 Diabetes.

BACKGROUND: Clinical inertia in type 2 diabetes mellitus (T2DM) refers to the failure of clinicians to intensify therapy when indicated. Many T2DM patients remain suboptimally controlled after initiating basal insulin. OBJECTIVE: To examine the prevalence of patients treated with basal insulin but in poor glycemic control (hemoglobin A1c [A1c] ≥ 7%) after initiation and subsequent treatment intensification patterns and glycemic outcomes in a real-world setting. METHODS: Adults diagnosed with T2DM newly initiating a basal insulin analog (insulin glargine or detemir) from January 2010 to September 2014 were identified in the QuintilesIMS Real-World Data Adjudicated Claims linked to the QuintilesIMS Real-World Data Electronic Medical Records. Patients were previously naive to insulin and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), were persistent on therapy for ≥ 6 months, and had ≥ 12 months of continuous health plan enrollment after initiation. First treatment intensification (increase in basal insulin dose [of ≥ 10%], addition of bolus insulin, GLP-1 RA, or a new oral antidiabetic drug [OAD]) was assessed among patients in poor glycemic control at 6 months after initiation over the available (minimum ≥ 12-month) follow-up. Subsequent glycemic outcomes and treatment intensification were assessed. Kaplan-Meier (KM) analysis evaluated time-to-treatment intensification and time to A1c goal. RESULTS: Of 427 eligible patients with A1c available at 6 months, 59.3% were male; mean age was 53.9 years; mean follow-up was 29.4 months; and mean dose of the initiated prescription was 29.6 insulin units (U) (median 24U). Six months after initiating basal insulin, 81.0% of patients (n = 346) remained in poor glycemic control, and mean basal insulin dose was 31.0U (median 25U). Most (88.4%; n = 306) of these uncontrolled patients subsequently intensified treatment over the available follow-up. Using KM analysis, these patients intensified treatment in a median of 58 days (range: 17.5 days [GLP-1 RA addition] to 52 days [increase in basal insulin dose]) from the first elevated A1c measurement taken after 6 months, and 72.5% (GLP-1 RA addition) to 91.1% (OAD addition) of patients continued to remain in poor glycemic control at 12 months after intensification. Most patients (66.8%; n = 231/346) first intensified treatment by increasing their basal insulin dose, and mean dose increased to 61.7U (median 38U) at intensification. Six months following basal insulin increase, almost all patients remained on basal insulin therapy and among those with available A1c, 92.1% (140 of 152) were in poor glycemic control. In the subsequent 12 months, only a third (34%) of uncontrolled patients added another antihyperglycemic agent. CONCLUSIONS: The vast majority of patients remained uncontrolled in the 6 months following basal insulin initiation. Basal insulin up-titration was slow and insufficient in the 6 months after initiation, indicating treatment inertia. Subsequently, most patients failed to achieve glycemic targets despite intensification with basal insulin. This finding suggests a substantial unmet need for effective treatment intensification among T2DM patients treated with basal insulin who remain uncontrolled. Improved provider education and guidelines on appropriate intensification are warranted. DISCLOSURES: This study was funded by Novo Nordisk. Mocarski, Guerrero, Langer, and Thorsted are employees and shareholders of Novo Nordisk. Yeaw, Divino, and DeKoven are employed by QuintilesIMS, which received remuneration from Novo Nordisk for work on this study. Study concept and design were contributed by Mocarski, DeKoven, Langer, and Thorsted. Yeaw took the lead in data collection, along with Divino and DeKoven. Data interpretation was performed by Yeaw, Divino, DeKoven, and Guerrero. The manuscript was written by Mocarski and Divino and revised by Guerrero, Langer, and Thorsted, along with Yeaw and DeKoven. Some of the data from this study were presented via poster at the AMCP Annual Meeting in March 2017 and at the 53rd EASD Annual Meeting in September 2017.

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.

POSTPRANDIAL DOSING OF BOLUS INSULIN IN PATIENTS WITH TYPE 1 DIABETES: A CROSS-SECTIONAL STUDY USING DATA FROM THE T1D EXCHANGE REGISTRY.

OBJECTIVE: To assess the prevalence and characteristics of patients with type 1 diabetes (T1D) who dose bolus insulin postprandial (PostP) versus preprandial (PreP). METHODS: Data for this cross-sectional study were obtained from 21,533 participants in the T1D Exchange Registry. Data were drawn from the enrollment questionnaire. Patients who dosed 'immediately before meal' or 'several minutes before meal' were classified as PreP. Patients who dosed 'during meal' or 'after meal' were classified as PostP. Data reported (PostP vs. PreP) are mean ± SD and percentage, as appropriate. RESULTS: After exclusion of patients who did not answer the dose-timing question or who selected 'not given regularly' or 'depends on glucose level prior to meal,' (4,229 of 25,762), 21,533 patients were included in the study. Ninety-nine percent of patients used rapid-acting insulin analogues; 32% dosed insulin PostP. Compared to PreP, children <18 years of age dosing PostP were characterized by higher glycated hemoglobin (HbA1c) (8.7 ± 1.5% [72 ± 16.4 mmol/mol] vs. 8.4 ± 1.7% [68 ± 18.6 mmol/mol]), larger insulin dose (1.2 ± 0.7 IU/kg/day vs. 1.1 ± 0.7 IU/kg/day), greater prevalence of history of hypoglycemia, and diabetic ketoacidosis. Adults who dosed PostP were characterized by younger age (33.0 ± 15.3 years vs. 39.5 ± 16.6 years), higher HbA1c (8.3 ± 1.5% [67 ± 16.4 mmol/mol] vs. 7.8 ± 1.5% [62 ± 16.4 mmol/mol]), and larger insulin dose (1.0 ± 0.6 IU/kg/day vs. 0.9 ± 0.5 IU/kg/day) than PreP. CONCLUSION: This study reveals that a large proportion of patients dose bolus insulin PostP. Despite the use of current rapid-acting insulin analogues, patients who dose PostP are characterized by poorer glycemic control in all patients and a greater prevalence of history of severe hypoglycemia and diabetic ketoacidosis in children. ABBREVIATIONS: BMI = body mass index; CGM = continuous glucose monitoring; DKA = diabetic ketoacidosis; HbA1c = glycated hemoglobin; PostP = postprandial; PreP = preprandial; SMBG = self-monitored blood glucose; T1D = type 1 diabetes.

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.

Increased Risk of Severe Hypoglycemic Events with Increasing Frequency of Non-severe Hypoglycemic Events in Patients with Type 1 and Type 2 Diabetes.

INTRODUCTION: Severe hypoglycemic events (SHEs) are associated with significant morbidity, mortality and costs. However, the more common non-severe hypoglycemic events (NSHEs) are less well explored. We investigated the association between reported frequency of NSHEs and SHEs among patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the PREDICTIVE study. METHODS: PREDICTIVE was a global, prospective, observational study. Patients with T1DM (n = 7,420) or T2DM (n = 12,981), starting treatment with insulin detemir, reported the number of NSHEs and SHEs experienced during the 4 weeks prior to baseline and follow-up visits (mean 14.4 weeks). Logistic regression was used to determine the odds ratio (OR) of experiencing ≥1 SHE, in patients having 1-4 or ≥5 NSHEs, versus those having 0 NSHEs, while controlling for baseline covariates. RESULTS: Hypoglycemia rates were lower at follow-up than baseline. At baseline 59.2% (T1DM) and 18.8% (T2DM) reported any hypoglycemia and at follow-up 39.5% (T1DM) and 8.6% (T2DM). There was a significant (P < 0.0001) increase in the odds of ≥1 SHEs with increasing frequency of NSHEs in T1DM and T2DM, for both crude and adjusted estimates. At baseline, in T1DM, ORs for ≥1 SHE were 1.92 and 2.13 for 1-4 and ≥5 NSHEs, respectively; the corresponding ORs in T2DM were 10.83 and 15.36, respectively. At follow-up, the ORs for ≥1 SHE were 2.01 and 3.20 (T1DM) and 18.99 and 24.29 (T2DM) for 1-4 and ≥5 NSHEs, respectively. CONCLUSION: A statistically significant association between NSHE and SHE frequency was found in T1DM and T2DM. These data provide a clear rationale for the reduction of hypoglycemic events, regardless of severity, while striving for optimal glycemic control.

Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people.

OBJECTIVE: To determine time to treatment intensification in people with type 2 diabetes treated with one, two, or three oral antidiabetes drugs (OADs) and associated levels of glycemic control. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study based on 81,573 people with type 2 diabetes in the U.K. Clinical Practice Research Datalink between January 2004 and December 2006, with follow-up until April 2011. RESULTS: In people with HbA1c ≥7.0, ≥7.5, or ≥8.0% (≥53, ≥58, or ≥64 mmol/mol), median time from above HbA1c cutoff to intensification with an additional OAD was 2.9, 1.9, or 1.6 years, respectively, for those taking one OAD and >7.2, >7.2, and >6.9 years for those taking two OADs. Median time to intensification with insulin was >7.1, >6.1, or 6.0 years for those taking one, two, or three OADs. Mean HbA1c at intensification with an OAD or insulin for people taking one, two, or three OADs was 8.7, 9.1, and 9.7%. In patients taking one, two, or three OADs, median time from treatment initiation to intensification with an OAD or insulin exceeded the maximum follow-up time of 7.2 years. The probability of patients with poor glycemic control taking one, two, or three OADs, intensifying at end of follow-up with an OAD, was 21.1-43.6% and with insulin 5.1-12.0%. CONCLUSIONS: There are delays in treatment intensification in people with type 2 diabetes despite suboptimal glycemic control. A substantial proportion of people remain in poor glycemic control for several years before intensification with OADs and insulin.

Risk of breast cancer after false-positive test results in screening mammography.

BACKGROUND: Screening for disease in healthy people inevitably leads to some false-positive tests in disease-free individuals. Normally, women with false-positive screening tests for breast cancer are referred back to routine screening. However, the long-term outcome for women with false-positive tests is unknown. METHODS: We used data from a long-standing population-based screening mammography program in Copenhagen, Denmark, to determine the long-term risk of breast cancer in women with false-positive tests. The age-adjusted relative risk (RR) of breast cancer for women with a false-positive test compared with women with only negative tests was estimated with Poisson regression, adjusted for age, and stratified by screening round and technology period. All statistical tests were two-sided. RESULTS: A total of 58 003 women, aged 50-69 years, were included in the analysis. Women with negative tests had an absolute cancer rate of 339/100 000 person-years at risk, whereas women with a false-positive test had an absolute rate of 583/100 000 person-years at risk. The adjusted relative risk of breast cancer after a false-positive test was 1.67 (95% confidence interval [CI] 1.45 to 1.88). The relative risk remained statistically significantly increased 6 or more years after the false-positive test, with point estimates varying between 1.58 and 2.30. When stratified by assessment technology phase and using equal follow-up time, the false-positive group from the mid 1990s had a statistically significantly higher risk of breast cancer (RR = 1.65, 95% CI = 1.22 to 2.24) than the group with negative tests, whereas the false-positive group from the early 2000s was not statistically significantly different from the group testing negative. CONCLUSIONS: The implementation of new assessment technology coincided with a decrease in the size of excess risk of breast cancer for women with false-positive screening results. However, it may be beneficial to actively encourage women with false-positive tests to continue to attend regular screening.

Exposure to tetrachloroethylene in dry cleaning shops in the Nordic countries.

OBJECTIVES: Tetrachloroethylene is the dominant solvent used in dry cleaning worldwide and many workers are potentially exposed. We report here on results of 1296 measurements of tetrachloroethylene undertaken in Nordic dry cleaning shops 1947-2001. METHODS: We searched documents and files in the Nordic institutes of occupational health for air measurements of tetrachloroethylene. Repeated measurements from the same facility during a short time interval were registered only once using the time-weighted average. We registered also changes over time in occupational exposure limits (OELs) to tetrachloroethylene. RESULTS: Only scattered measurements were available from the early years, and the exposure level seemed fairly stable up until the mid 1970s. The median exposure level was 20 p.p.m. in 1976 and decreased to 3 p.p.m. in 2000. Exposure levels in the four Nordic countries followed similar trends. In the late 1960s, the OELs varied between the Nordic countries from 30 to 100 p.p.m. Sweden was first to lower the limit, but limits gradually converged over time. At present, Denmark, Finland, and Sweden use 10 p.p.m., while Norway uses 6 p.p.m. Over time, the average observed exposure level was lower than the OEL in all countries, but in Denmark and Sweden, up to one-third of measured exposures exceeded the OEL. Overall, the stationary measurements for maintenance work showed 36 p.p.m., while the personal measurements showed 7.5 p.p.m. for dry cleaners and 6.25 p.p.m. for shop assistants. CONCLUSION: The Nordic data illustrate that it is possible over time to control chemical exposures even in an industry consisting of many small and scattered work places.