Healthcare resource utilization in patients with pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD): a real-world data analysis.

RATIONALE: There is a lack of real-world characterization of healthcare costs and associated cost drivers in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (PH-COPD). OBJECTIVES: To examine (1) excess healthcare resource utilization (HCRU) and associated costs in patients with PH-COPD compared to COPD patients without PH; and (2) patient characteristics that are associated with higher healthcare costs in patients with PH-COPD. METHODS: This study analyzed data from the IQVIA PharMetrics® Plus database (OCT2014-MAY2020). Patients with PH-COPD were identified by a claims-based algorithm based on PH diagnosis (ICD-10-CM: I27.0, I27.2, I27.20, I27.21, I27.23) after COPD diagnosis. Patients aged ≥40 years and with data available ≥12 months before (baseline) and ≥6 months after (follow-up) the first observed PH diagnosis were included. Patients with other non-asthma chronic pulmonary diseases, PH associated with other causes, cancer, left-sided heart failure (HF), PH before the first observed COPD diagnosis, or right-sided/unspecified HF during baseline were excluded. Patients in the PH-COPD cohort were matched 1:1 to COPD patients without PH based on propensity scores derived from baseline patient characteristics. Annualized all-cause and COPD/PH-related (indicated by a primary diagnosis of COPD or PH) HCRU and costs during follow-up were compared between the matched cohorts. Baseline patient characteristics associated with higher total costs were examined in a generalized linear model in the PH-COPD cohort. RESULTS: A total of 2,224 patients with PH-COPD were identified and matched to COPD patients without PH. Patients with PH-COPD had higher all-cause HCRU and annual healthcare costs ($51,435 vs. $18,412, p<0.001) than matched COPD patients without PH. Among patients with PH-COPD, costs were primarily driven by hospitalizations (57%), while COPD/PH-related costs accounted for 13% of all-cause costs. Having a higher comorbidity burden and a prior history of COPD exacerbation were major risk factors for higher total all-cause costs among patients with PH-COPD. CONCLUSIONS: Treatment strategies focusing on preventing hospitalizations and managing comorbidities may help reduce the burden of PH-COPD.

Addressing Therapeutic Inertia: Development and Implementation of an Electronic Health Record-Based Diabetes Intensification Tool.

Objective: To assess whether an electronic health record (EHR)-based diabetes intensification tool can improve the rate of A1C goal attainment among patients with type 2 diabetes and an A1C ≥8%. Methods: An EHR-based tool was developed and sequentially implemented in a large, integrated health system using a four-phase, stepped-wedge design (single pilot site [phase 1] and then three practice site clusters [phases 2-4]; 3 months/phase), with full implementation during phase 4. A1C outcomes, tool usage, and treatment intensification metrics were compared retrospectively at implementation (IMP) sites versus nonimplementation (non-IMP) sites with sites matched on patient population characteristics using overlap propensity score weighting. Results: Overall, tool utilization was low among patient encounters at IMP sites (1,122 of 11,549 [9.7%]). During phases 1-3, the proportions of patients achieving the A1C goal (<8%) were not significantly improved between IMP and non-IMP sites at 6 months (range 42.9-46.5%) or 12 months (range 46.5-53.1%). In phase 3, fewer patients at IMP sites versus non-IMP sites achieved the goal at 12 months (46.7 vs. 52.3%, P = 0.02). In phases 1-3, mean changes in A1C from baseline to 6 and 12 months (range -0.88 to -1.08%) were not significantly different between IMP and non-IMP sites. Times to intensification were similar between IMP and non-IMP sites. Conclusion: Utilization of a diabetes intensification tool was low and did not influence rates of A1C goal attainment or time to treatment intensification. The low level of tool adoption is itself an important finding highlighting the problem of therapeutic inertia in clinical practice. Testing additional strategies to better incorporate, increase acceptance of, and improve proficiency with EHR-based intensification tools is warranted.

Erratum: Addressing Therapeutic Inertia: Development and Implementation of an Electronic Health Record-Based Diabetes Intensification Tool. Diabetes Spectrum 2023;36:161-170 (https://doi.org/10.2337/ds22-0031).

[This corrects the article DOI: 10.2337/ds22-0031.].

Medication use by US patients with pulmonary hypertension associated with chronic obstructive pulmonary disease: a retrospective study of administrative data.

BACKGROUND: Pulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD). While clinical guidelines recommend specific drug therapies for pulmonary arterial hypertension (PAH), these drug therapies are not recommended for PH due to lung disease. METHODS: This was a retrospective cohort study using the Optum® Clinformatics® Data Mart from January 2009-September 2019. An algorithm was designed to identify adults with ≥ 2 ICD-9-CM or ICD-10-CM diagnosis codes for PH and with ≥ 2 diagnosis codes for COPD. Sensitivity analyses were conducted among subgroups of patients with evidence of a right heart catheterization (RHC) or pulmonary function test (PFT). Patient characteristics, medications used, and durations of use of PAH and COPD medications were analyzed. RESULTS: A total of 25,975 patients met the study inclusion criteria. Their mean age was 73.5 (SD 10.0) years and 63.8% were female. Medications targeting PAH were prescribed to 643 (2.5%) patients, most frequently a phosphodiesterase-5 inhibitor (2.1%) or an endothelin receptor antagonist (0.75%). Medications for COPD were prescribed to 17,765 (68.4%) patients, most frequently an inhaled corticosteroid (57.4%) or short-acting beta agonist (50.4%). The median durations of use ranged from 4.9 to 12.8 months for PAH medications, and from 0.4 to 5.9 months for COPD medications. Of the subgroup of patients with RHC (N = 2325), 257 (11.1%) were prescribed a PAH medication and 1670 (71.8%) used a COPD medication. Of the subgroup with a PFT (N = 2995), 58 (1.9%) were prescribed a PAH medication and 2100 (70.1%) a COPD medication. CONCLUSIONS: Patients with PH associated with COPD were identified in a US administrative claims database. Very few of these patients received any of the medications recommended for PAH, and only about two thirds received medications for COPD.

Excess healthcare resource utilization and costs for commercially insured patients with pulmonary arterial hypertension: A real-world data analysis.

This retrospective study was conducted to evaluate all-cause healthcare resource utilization (HCRU) and costs in commercially insured patients living with pulmonary arterial hypertension (PAH) and explore end-of-life (EOL)-related HCRU and costs. Data from the IQVIA PharMetrics® Plus database (October 2014 to May 2020) were analyzed to identify adults (≥18 years) with PAH (PAH cohort) and those without PH (non-PH cohort). Patients were required to have data for ≥12 months before (baseline) and ≥6 months after (follow-up) the first observed PH diagnosis (index date) for PAH cohort or pseudo index date for non-PH cohort. A PAH EOL cohort was similarly constructed using a broader data window (October 2014 to March 2022) and ≥1 month of follow-up. Annualized all-cause HCRU and costs during follow-up were compared between PAH and non-PH cohorts after 1:1 matching on propensity scores derived from patient characteristics. EOL-related HCRU and costs were explored within 30 days and 6 months before the death date and estimated by a claims-based algorithm in PAH EOL cohort. The annual all-cause total ($183,616 vs. $20,212) and pharmacy ($115,926 vs. $7862; both p < 0.001) costs were 8 and 14 times higher, respectively, in the PAH cohort versus matched non-PH cohort (N = 386 for each). In PAH EOL cohort (N = 28), the mean EOL-related costs were $48,846 and $167,524 per patient within 30 days and 6 months before the estimated death, respectively. Hospitalizations contributed 58.8%-70.8% of the EOL-related costs. The study findings indicate substantial HCRU and costs for PAH. While pharmacy costs were one of the major sources, hospitalization was the primary driver for EOL-related costs.

Suboptimal adherence to food restrictions requirements related to drug regimens for chronic diseases.

BACKGROUND: Oral medications for chronic conditions often involve a variety of instructions, including time of day/dosing, drug interactions, and food intake restrictions. However, the extent to which patients follow these instructions is unclear. METHODS: We surveyed patients from the US and Europe (UK, France, Germany, Italy, Spain) who were prescribed sulfonylureas (SU: glimepiride, glipizide, or gliclazide) for diabetes or levothyroxine for hypothyroidism. Patients kept a daily diary for 3-5 days documenting their adherence to three criteria: dosing regimen including time of day, warning labels including drug interactions, and food restrictions. RESULTS: A total of 421 US and 493 European patients took the study medications; 546 patients took SU and 368 took levothyroxine. Overall, 48% of patients were males; 46% were age 65 years or older. Despite most patients having received instructions on medication requirements (US 71%, EU 75%), most patients reported being only somewhat knowledgeable (US 69%; EU 71%). Adherence, measured by the proportion of the days a participant was adherent to each category out of the observational period (ranging from 3-5 days), varied by type of instruction, with the poorest adherence observed for food restriction requirements (US 34% of the observation days, EU 26%) compared to warning labels (US 77%, EU 67%) and dosing regimen (US 85%, EU 87%). CONCLUSIONS: Patients adhered to dosing and cautionary instructions across the majority of the study period but were largely non-adherent to food intake restrictions. Improved communication and increased emphasis on food intake restrictions is needed when advising patients on their medications.

Real-world weight change, adherence, and discontinuation among patients with type 2 diabetes initiating glucagon-like peptide-1 receptor agonists in the UK.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a type 2 diabetes mellitus (T2DM) treatment with demonstrated weight loss benefits in clinical trials. However, the extent to which real-world patients with T2DM achieve clinically meaningful weight loss (≥5%) has not been well characterized. Analysis of real-world data suggests adherence to injectable GLP-1 RAs is suboptimal and discontinuation following the first year of therapy is poorly characterized. RESEARCH DESIGN AND METHODS: A retrospective cohort study among patients with T2DM initiating injectable GLP-1 RA therapy was conducted using the Clinical Practice Research Datalink that includes primary care medical records for 13 million patients in the UK. This study assessed weight change, adherence (proportion of days covered (PDC) ≥80%), and discontinuation (≥90-day gap between prescriptions) at 12 and 24 months during the study period spanning January 2009-December 2017. RESULTS: Among 589 patients initiating a GLP-1 RA, 56.4% were female and the median age was 54 years (IQR (46, 61)). The median body mass index was 41.2 kg/m2 (IQR (35.8, 46.4)). Among patients with weight measures available (n=341 at 12 months; n=232 at 24 months), 33.4% and 43.5% achieved weight loss ≥5% of baseline weight at 12 and 24 months, respectively. At 12 and 24 months, 64.5% and 59.2% were adherent, and 45.2% and 64.7% discontinued, respectively. CONCLUSIONS: A minority of patients initiating GLP-1 RAs achieved ≥5% weight loss, suggesting the real-world benefit of these agents on weight loss may be lower than that observed in clinical trials. Patients on GLP-1 RAs may benefit from additional support to improve long-term adherence.

Hemoglobin A1C testing frequency among patients with type 2 diabetes within a US payer system: a retrospective observational study.

OBJECTIVE: The American Diabetes Association (ADA) guidelines recommend A1C testing schedules for patients with type 2 diabetes; however, level of real-world guideline adherence remains unclear. The current study evaluated A1C testing frequency and its association with glycemic control and cardiovascular outcomes. METHODS: A retrospective study was conducted utilizing Aetna's Enterprise Data Warehouse. Adult patients with a medical claim for type 2 diabetes in 2017 (index date) were included. Patients had continuous enrollment through December 2019 and ≥1 reported A1C measurement from 2017 to 2019. Follow-up was up to 36 months post-index date. RESULTS: Of the 112,572 eligible patients, 50.0% were female and median age was 70 years; 32.9% of patients with controlled baseline A1C (<8%, 64 mmol/mol) received less than the 2 tests/year recommended by the ADA, while 60.6% of patients with uncontrolled baseline A1C received less than the quarterly testing recommended by the ADA. More frequent testing was associated with age (65-75 years), uncontrolled baseline A1C and presence of comorbidities. In separate multivariable models, 2-3 A1C tests/year were associated with greater likelihood of A1C < 8% (64 mmol/mol) vs. <2 tests/year (OR = 1.07, 95% confidence interval [CI] 1.02-1.12), while >3 tests/year was associated with a modestly increased risk of cardiovascular events vs. <2 tests/year (OR = 1.08, 95% CI 1.01-1.15). CONCLUSIONS: A large proportion of type 2 diabetes patients were not tested per guideline recommendations. The relationship between A1C testing frequency and glycemic control was inconsistent, though there was a significant association between more frequent testing and experiencing a CV event.

Secondary metformin monotherapy failure in individuals with type 2 diabetes mellitus.

INTRODUCTION: To assess secondary metformin monotherapy (MM) failure in a real-world type 2 diabetes mellitus (T2DM) cohort. RESEARCH DESIGN AND METHODS: Using the IQVIA Electronic Medical Record (formerly GE Centricity) database, adults with T2DM who initiated MM between January 1, 2012 and June 30, 2016 and achieved glycemic control (hemoglobin A1c (HbA1c) <7% (53 mmol/mol); index date) were analyzed. Secondary MM failure was defined in two ways: loss of glycemic control (HbA1c ≥7% (53 mmol/mol)) and treatment change (addition or switch of antihyperglycemic agent). Multivariable logistic regression models assessed the association between secondary MM failure and sociodemographic and clinical factors. RESULTS: The analysis included 4775 patients initiating MM. 32.9% and 19.2% experienced secondary MM failure at 24 months measured as loss of glycemic control and treatment change, respectively. Multivariable logistic regression found that women (OR=1.3, 95% CI 1.1 to 1.5) compared with men, lower Charlson Comorbidity Index (CCI) (OR=0.89, 95% CI 0.86 to 0.93), and lower baseline HbA1c (OR=0.93, 95% CI 0.88 to 0.98) were associated with increased likelihood of loss of glycemic control. Lower CCI was associated with increased likelihood of treatment change (OR=0.78, 95% CI 0.75 to 0.82). CONCLUSIONS: The observed frequency of secondary MM failure underscores the importance of the American Diabetes Association's recommendation for glycemic monitoring of at least every 6 months so that timely therapeutic adjustments can be made.

Cost-effectiveness of intensification with SGLT2 inhibitors for type 2 diabetes.

OBJECTIVES: Using a US payer perspective, this study aimed to compare the lifetime cost-effectiveness of adding sodium-glucose cotransporter 2 (SGLT2) inhibitors vs switching to glucagon-like peptide 1 receptor agonists (GLP-1 RAs) among patients with type 2 diabetes who were not at glycated hemoglobin A1c target after dual therapy with metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. STUDY DESIGN: The cost-effectiveness analysis was performed with the validated IQVIA Core Diabetes Model. Treatment effects were obtained from randomized clinical trials with economic data based on published literature. METHODS: Risk of treatment-emergent adverse events and complications were simulated using submodels informed by published risk equations adjusted for patient characteristics, physiological parameters, and history of complications. Outcomes included cumulative incidence of micro- and macrovascular complications, life-years (LYs), quality-adjusted life-years (QALYs), and total costs. Scenario analyses were performed to assess robustness of results to variations in clinical and cost inputs and assumptions. RESULTS: Over a lifetime time horizon, adding an SGLT2 inhibitor dominated the strategy of switching to a GLP-1 RA, improving survival by 0.049 LYs and 0.026 QALYs, and was associated with cost savings of $9511. The majority of the scenario analyses confirmed dominance of the DPP-4 inhibitor + SGLT2 inhibitor pathway vs the GLP-1 RA pathway. The probabilistic sensitivity analysis reinforced the base-case finding of cost savings while gaining QALYs. CONCLUSIONS: Intensification with an SGLT2 inhibitor on top of a DPP-4 inhibitor demonstrated slightly better efficacy and cost savings compared with switching to a GLP-1 RA in patients not at glycemic goal with metformin and a DPP-4 inhibitor.

Prevalence and incidence of microvascular and macrovascular complications over 15 years among patients with incident type 2 diabetes.

INTRODUCTION: Type 2 diabetes (T2D) is a common condition that, if left untreated or poorly managed, can lead to adverse microvascular and macrovascular complications. We estimated the prevalence and incidence of microvascular and macrovascular complications among patients newly diagnosed with T2D within a US integrated healthcare system. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study among patients newly diagnosed with T2D between 2003 and 2014. We evaluated 13 complications, including chronic kidney disease (CKD), cardiovascular disease (CVD), and all-cause mortality through 2018. Multivariable Cox proportional hazards models were used to study factors associated with complications. RESULTS: We identified 135 199 patients with incident T2D. The mean age was 58 years, and 48% were women. The prevalence of CKD was the highest of the complications at the time of T2D diagnosis (prevalence=12.3%, 95% CI 12.2% to 12.5%), while the prevalence of CVD was among the lowest at 3.3% (95% CI 3.2% to 3.3%). The median time to incidence of a T2D complication ranged from 3.0 to 5.2 years. High incidence rates (95% CI) of T2D complications included peripheral neuropathy (26.9, 95% CI 26.5 to 27.3 per 1000 person-years (PY)), CKD (21.2, 95% CI 20.9 to 21.6 per 1000 PY), and CVD (11.9, 95% CI 11.7 to 12.2 per 1000 PY). The trend of 5-year incidence rates of T2D complications by diagnosis year decreased over time (p value<0.001). Older age, non-Hispanic white race/ethnicity, sex, higher A1C, smoking, and hypertension were associated with increased CKD and CVD incidence. CONCLUSION: Though incidence rates of T2D complications were lower in more recent years (2010-2014), a significant proportion of patients had complications at T2D diagnosis. Earlier preventive therapies as well as managing modifiable factors may help delay the development and progression of T2D complications.

Metformin adherence and discontinuation among patients with type 2 diabetes: A retrospective cohort study.

AIMS: To describe discontinuation and adherence to metformin in the United Kingdom. METHODS: This was a retrospective analysis of data from the Clinical Practice Research Datalink database of type 2 diabetes patients aged ≥18 years with ≥1 metformin prescription in 2013. Metformin use was assessed in new and ongoing users, defined, respectively, as not having or having a prescription for metformin in the baseline period. Discontinuation was assessed in all patients and adherence in patients who did not discontinue metformin. Factors predictive of discontinuation and adherence were assessed. RESULTS: Discontinuation among new and ongoing users was 35.9% and 23.1%, respectively. Among the continuers of metformin treatment, the adherence rate was 40.5% and 44.3% among new and ongoing users, respectively. Among new users, baseline use of DDP-4 inhibitors (HR 1.276) and diabetes duration (HR 1.013) were associated with an increased risk of discontinuation, whereas increased age (HR 0.997), concomitant lipid-lowering therapy (HR 0.956), macrovascular disease (HR 0.952), and chronic kidney disease (HR 0.952) were associated with a decreased risk of discontinuation among ongoing users. Variables positively associated with adherence in both user groups were (HR values for all patients) age (1.021), smoking status (1.188), and baseline comorbidities: chronic kidney disease, depression, dementia, and chronic obstructive pulmonary disease (1.106, 1.192, 2.27, and 1.211, respectively), while obesity (0.936) and HbA1c 8.0-8.9% (0.862; reference <6.5%) were negatively associated with adherence. CONCLUSIONS: About one-third of patients initiating metformin discontinued within 12 months and fewer than 50% of all patients are adherent to metformin.

Real-World Adherence and Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists Therapy in Type 2 Diabetes Mellitus Patients in the United States.

AIM: To assess adherence and discontinuation of injectable glucagon-like peptide-1 receptor agonists (GLP-1 RA) at 12 and 24 months among adult type 2 diabetes mellitus (T2DM) patients in the United States initiating GLP-1 RA using the administrative claims-based database, Optum Clinformatics® Data Mart 7.1. METHODS: A retrospective study was conducted from 01/2009 to 12/2017. Patients were required to be continuously enrolled for 12 months prior to their first GLP-1 RA prescription. Proportion of days covered (PDC) from prescription claims ≥0.80 defined adherence. Discontinuation was defined as a ≥90-day gap from the last date of GLP-1 RA supply to the first date of subsequent prescription claim. RESULTS: A total of 4791 T2DM patients had ≥1 and 3907 had ≥2 GLP-1 RA prescription claims. 50.9% and 47.4% of patients were adherent at 12 and 24 months, respectively. Adherence was significantly higher among patients on weekly vs daily doses (p<0.001). Median time to discontinuation was 13 months. The discontinuation rate was 47.7% and 70.1% at 12 and 24 months, respectively, with differences at 24 months for age and dosing frequency (p<0.001 for both). CONCLUSION: Over half of T2DM patients initiating GLP-1 RA were non-adherent and the majority (70.1%) discontinued therapy by 24 months. Reasons for non-adherence and discontinuation merit further research.

Time in suboptimal glycemic control over 10 years for patients newly diagnosed with type 2 diabetes.

OBJECTIVE: To estimate time in suboptimal glycemic control among patients with incident type 2 diabetes (T2D) over 10 years. METHODS: We calculated percent of time in suboptimal glycemic control using three A1C thresholds (8%, 7.5%, 7%) following T2D diagnosis. Stratified analyses were conducted based on age and A1C levels at T2D diagnosis. RESULTS: We identified 28,315 patients with incident T2D. Percent of time in suboptimal glycemic control increased with T2D duration. Mean percent time in suboptimal A1C control in the first 2 years following diagnosis was 30%, 34% and 40% for the 8%, 7.5%, and 7% thresholds, respectively. In the 6-10 years following T2D diagnosis, the percent time in suboptimal A1C control increased to 39%, 48% and 61%, for the 8%, 7.5%, and 7% thresholds, respectively. Time in suboptimal glycemic control was longer among younger patients aged 20-44 versus ≥65 years and those with higher A1C (>8%) versus lower A1C (<7%) at diagnosis. CONCLUSIONS: Over 10 years following diagnosis, T2D patients spent one-third to over one-half of their time in suboptimal glycemic control. Reducing time spent above desired A1C targets could lower risk of microvascular and macrovascular complications.