The economic value of insulin glargine 300 U/mL (Gla-300) in people ≥18 years of age with type 2 diabetes mellitus: a value-based economic model from a U.S. payer perspective.

AIMS: This study aimed to evaluate the value and affordability of insulin glargine 300 U/mL (Gla-300) in a budget impact model from a United States (U.S.) payer perspective by leveraging recent real-world evidence (RWE) studies and incorporating the recent insulin price caps where applicable. MATERIALS AND METHODS: An economic model for a hypothetical one million U.S. health-plan population was developed to assess the budgetary impact of therapeutic interchanges in either direction between the two long- and longer-acting basal insulins (BIs) for patients with type 2 diabetes over a three-year model horizon. The utilization of long-acting BIs, longer-acting BIs, biosimilar BIs, and insulin degludec (IDeg-100) were informed by IQVIA data and internal forecasting at Sanofi. The DELIVER-2 and DELIVER-naïve studies provided healthcare resource utilization (HCRU) parameters. In the model base case, 24% of patients switched from long-acting BIs to insulin glargine biosimilars, IDeg-100, and other longer-acting BIs (Gla-300) by projected year 3. RESULTS: The base case total costs were $10,145 per patient per year (PPPY) in year 3 for the cumulative population. When all patients switched to Gla-300, the total costs in year 3 were $8,799, reflecting a net savings of -$660 PPPY compared to the budget increase of $686 PPPY in the base case. However, the longer-acting to long-acting BIs reversal scenario demonstrated a budgetary decrease of $676 PPPY over the model horizon. The reduction in incremental PPPY cost of $93 was observed using net drug costs rather than wholesale acquisition costs (WAC). LIMITATIONS: The market shares for years 1-3 were based on expectations supported by the clinicians' expert opinions and were not obtained from real-world data. CONCLUSIONS: The economic value of increased utilization of Gla-300 was driven by the reduction in HCRU, costs and market shares assumptions. Budgetary reductions were achieved by switching patients from long-acting BIs to Gla-300.

Type 2 Diabetes (T2D) is a chronic and debilitating condition that can lead to severe macro or microvascular complications. To mitigate these complications, it is crucial to effectively manage blood glucose levels. When other treatments prove ineffective in achieving adequate glucose control, insulin-based therapy becomes necessary. However, insulin-based treatments often come with the risk of hypoglycemic episodes, which can lead to increased utilization of healthcare resources (HCRU) and have a negative impact on costs.This study aimed to assess the budgetary impact of higher market shares of longer-acting basal insulins (specifically insulin glargine Gla-300) compared to long-acting basal insulins, insulin glargine biosimilars, and insulin degludec (IDeg) in the treatment of T2D. The perspective taken was that of a U.S. payer, taking into account the recent insulin price caps where applicable.The economic benefit of increased utilization of Gla-300 was driven by reductions in HCRU, costs, and market share assumptions. This resulted in a budgetary increase of $686 per patient per year (PPPY). In an alternative scenario where all patients transitioned to Gla-300, it led to a net savings of $660 PPPY.These findings provide valuable insights for decision-makers and healthcare professionals when making choices related to formulary placement and treatment utilization.

Budget Impact Analysis of Intensification with iGlarLixi Compared to Alternative Treatment Strategies Among Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: The clinical benefits of treating patients with type 2 diabetes mellitus (T2DM) with fixed-ratio combination of insulin iGlar (iGlar) plus lixisenatide (iGlarLixi) were demonstrated in clinical trials and real-world evidence studies; however, its cost impact to healthcare payers is unknown. METHODS: A budget impact model was developed from a United States (US) payer's perspective for a hypothetical healthcare plan of 1 million people over a 1-year time horizon. In scenario analysis, patients with uncontrolled glycated hemoglobin (HbA1c) treated with 60 units or less of daily insulin (insulin cohort) or oral antidiabetic drugs (OADs) only (OAD cohort) were intensified to iGlarLixi/rapid-acting insulin (RAI)/glucagon-like peptide 1 receptor agonists (GLP-1RA) or iGlarLixi/iGlar/GLP-1RA, respectively. Model inputs from real-world data (RWD) included baseline market shares, proportion of patients intensifying to respective treatments, and dosing inputs; unit costs were obtained from published literature. One-way sensitivity analyses assessed the impact of individual parameters. RESULTS: Intensification with iGlarLixi resulted in the lowest incremental per member per month (PMPM) budget impact compared to other intensifying drugs (iGlar, RAI, and GLP-1RA). In the insulin cohort, the incremental PMPM cost for intensification with iGlarLixi ($0.03) was the lowest among intensifying drugs; GLP-1RA ($72.20) and RAI ($4.81). Similarly, the incremental PMPM cost for intensification with iGlarLixi was the lowest ($1.25) in the OAD cohort among intensifying drugs; GLP-1RA ($321.65) and iGlar ($114.82). In scenario analyses, when equal market intensification shares for iGlarLixi and GLP-1RA were explored, the incremental PMPM cost for iGlarLixi ($0.03) remained lower than GLP-1RA ($2.28) and RAI ($10.44) in the insulin cohort. CONCLUSIONS: Intensification with iGlarLixi was associated with lower costs compared to other treatment intensifications, as well as overall budget reductions compared to pre-intensification when considering cost savings attributable to reduction in HbA1c; therefore, its inclusion for the treatment of T2DM would represent a budget saving.

Real-World Persistence, Adherence, Hypoglycemia, and Health Care Resource Utilization in People With Type 2 Diabetes Who Continued With the Second-Generation Basal Insulin Analog Insulin Glargine 300 Units/mL or Switched to a First-Generation Basal Insulin (Insulin Glargine 100 Units/mL or Detemir 100).

People with type 2 diabetes receiving a second-generation basal insulin (BI) analog may be switched to a first-generation formulation for financial reasons or changes in health insurance. However, because second-generation BI analogs have more even pharmacokinetic profiles, longer durations of action (>24 vs. ≤24 hours), and more stable action profiles than first-generation BI analogs, such a change may result in suboptimal treatment persistence and/or adherence. This study compared treatment persistence, treatment adherence, rates of hypoglycemia, and health care resource utilization outcomes in people with type 2 diabetes who either continued treatment with the second-generation BI Gla-300 or switched to a first-generation BI. The study showed that continuing with Gla-300 was associated with a lower risk of discontinuing therapy, fewer emergency department visits, and lower hypoglycemia event rates than switching to a first-generation BI.

Clinical and economic outcomes associated with use of anti-arrhythmic drugs versus ablation in atrial fibrillation.

Aim: To evaluate the clinical and economic impact of antiarrhythmic drugs (AADs) compared with ablation both as individual treatments and as combination therapy without/with considering the order of treatment among patients with atrial fibrillation (AFib). Materials & methods: A budget impact model over a one-year time horizon was developed to assess the economic impact of AADs (amiodarone, dofetilide, dronedarone, flecainide, propafenone, sotalol, and as a group) versus ablation across three scenarios: direct comparisons of individual treatments, non-temporal combinations, and temporal combinations. The economic analysis was conducted in accordance with CHEERS guidance as per current model objectives. Results are reported as costs per patient per year (PPPY). The impact of individual parameters was evaluated using one-way sensitivity analysis (OWSA). Results: In direct comparisons, ablation had the highest annual medication/procedure cost ($29,432), followed by dofetilide ($7661), dronedarone ($6451), sotalol ($4552), propafenone ($3044), flecainide ($2563), and amiodarone ($2538). Flecainide had the highest costs for long-term clinical outcomes ($22,964), followed by dofetilide ($17,462), sotalol ($15,030), amiodarone ($12,450), dronedarone ($10,424), propafenone ($7678) and ablation ($9948). In the non-temporal scenario, total costs incurred for AADs (group) + ablation ($17,278) were lower compared with ablation alone ($39,380). In the temporal scenario, AADs (group) before ablation resulted in PPPY cost savings of ($22,858) compared with AADs (group) after ablation ($19,958). Key factors in OWSA were ablation costs, the proportion of patients having reablation, and withdrawal due to adverse events. Conclusion: Utilization of AADs as individual treatment or in combination with ablation demonstrated comparable clinical benefits along with costs savings in patients with AFib.

Clinical Benefits of Treating Patients with Type 2 Diabetes Mellitus with iGlarLixi: A Patient-Level Simulation Study.

INTRODUCTION: The fixed-ratio combination of insulin glargine (iGlar) plus lixisenatide (iGlarLixi) has proven efficacious in clinical trials; however, there is limited evidence of its benefits in a variety of real-world patients with type 2 diabetes mellitus (T2DM) who present in routine clinical practice. METHODS: A large integrated claims and EHR database was used to identify two real-world (RW) cohorts (ages ≥ 18) with T2DM who were eligible for treatment with iGlarLixi. At baseline, the first cohort (insulin cohort) received insulin with or without oral antidiabetic drugs (OADs), and the second cohort (OAD-only cohort) received OADs only. A Monte Carlo patient-level simulation was applied to each cohort based on treatment strategies and efficacies from the LixiLan-L and LixiLan-O trials to estimate reductions in glycated hemoglobin A1C (A1C) and the percentage achieving age-based A1C goals (≤ 7% for ages < 65 and ≤ 8% for ages ≥ 65) at 30 weeks. RESULTS: The RW insulin (N = 3797) and OAD-only (N = 17,633) cohorts differed considerably in demographics, age, clinical characteristics, baseline A1C levels, and background OAD therapies compared to the populations in the Lixilan-L and Lixilan-O trials. Regardless of the cohort description, A1C goals were achieved among 52.6% vs. 31.6% (p < 0.001) of patients in the iGlarLixi vs. the iGlar arms in the insulin cohort simulation, while A1C goals were achieved among 59.9% vs. 49.3% and 32.8% (p < 0.001) of patients in the OAD-only cohort simulation in the iGlarLixi vs. the iGlar and lixisenatide arms, respectively. CONCLUSIONS: Irrespective of the treatment regimen at baseline (insulin vs. OAD only), this patient-level simulation demonstrated that a greater proportion of patients achieved their A1C goals with iGlarlixi compared to iGlar or lixisenatide alone. These findings suggest that the benefits of iGlarLixi extend to clinically distinct RW populations.

A value-based budget impact model for dronedarone compared with other rhythm control strategies.

Aim: The budgetary consequences of increasing dronedarone utilization for treatment of atrial fibrillation were evaluated from a US payer perspective. Materials & methods: A budget impact model over a 5-year time horizon was developed, including drug-related costs and risks for long-term clinical outcomes (LTCOs). Treatments included antiarrhythmic drugs (AADs; dronedarone, amiodarone, sotalol, propafenone, dofetilide, flecainide), rate control medications, and ablation. Direct comparisons and temporal and non-temporal combination scenarios investigating treatment order were analyzed as costs per patient per month (PPPM). Results: By projected year 5, costs PPPM for dronedarone versus other AADs decreased by $37.69 due to fewer LTCOs, treatment with dronedarone versus ablation or rate control medications + ablation resulted in cost savings ($359.94 and $370.54, respectively), and AADs placed before ablation decreased PPPM costs by $242 compared with ablation before AADs. Conclusion Increased dronedarone utilization demonstrated incremental cost reductions over time.

Patient and caregiver preferences for haemophilia A treatments: A discrete choice experiment.

INTRODUCTION: Long-acting products are changing the haemophilia A treatment landscape by giving patients and caregivers treatment options with varying product attributes. AIM: A discrete choice experiment (DCE) was used to elicit treatment attribute preferences among patients with haemophilia A and caregivers of children with haemophilia A. MATERIALS & METHODS: A survey of sociodemographics and preferences was completed by an online panel of adult patients with haemophilia A and caregivers of children (<18 years) with haemophilia A. The DCE included a series of questions in which respondents chose their preferred option from pairs of hypothetical treatment profiles with systematic variation in the levels of six attributes (safety concerns with too much clotting, bleed protection, dosing frequency, length of time the product has been approved for use, product type and joint health studies). Preference weights and relative attribute importance scores were estimated using random parameters logit models. RESULTS: One hundred and thirteen patients (mean age: 35.5 years) and 96 caregivers (mean age of child: 10.3 years) were included. For patients with haemophilia A, the top three attributes ranked from the most to least important were: (a) dosing frequency; (b) bleed protection; and (c) safety concerns with too much clotting. For caregivers of children with haemophilia A, the ranking was as follows: (a) safety concerns; (b) bleed protection; and (c) dosing. CONCLUSIONS: Patients with haemophilia A viewed dosing as the most important driver of treatment decision-making whereas caregivers of children with haemophilia A valued safety the most.

Limited Generalizability of a Retrospective Chart Review Comparing 3 Recombinant FVIII Products for Hemophilia A Prophylaxis.

DISCLOSURES: No funding supported the writing of this letter. Preblick, Ali, and DasMahapatra are employees and shareholders of Sanofi Genzyme. Gray is a postdoctoral fellow at Sanofi Genzyme and Rutgers University.

Estimation of Annual Health Care Costs for Adults with Type 1 Diabetes in the United States.

BACKGROUND: Diabetes health care resource utilization (HCRU) studies tend to focus on patients with type 2 diabetes (T2D) or pool patients with T2D and type 1 diabetes (T1D). There is a paucity of recent data on the cost of treating patients with T1D in the United States. OBJECTIVES: To (a) estimate the per-patient per-year (PPPY) HCRU and costs, from a payer perspective, associated with treating U.S. adults with T1D and (b) compare these with the HCRU and costs for patients with T2D. METHODS: This retrospective cohort study used claims data from the Optum Clinformatics database between January 2015 and December 2017. Adults (aged ≥ 18 years) with a diagnosis of T1D were propensity score-matched to adults with T2D. Overall and nondiabetes-related HCRU and costs were assessed for T1D and T2D and compared between the 2 groups. RESULTS: Propensity scores were used to match 10,103 patient pairs from T1D and T2D cohorts (mean ages 54.4 and 56.9 years, respectively). In the T1D cohort, inpatient, emergency department (ED), outpatient, and prescription claims occurred in 14.0%, 17.3%, 85.5%, and 100% of patients, respectively, resulting in a mean total cost of U.S. $18,817 PPPY (diabetes-related = $11,002; nondiabetes-related = $7,816). The T1D cohort had significantly higher mean total costs than the T2D cohort ($18,817 vs. $14,148 PPPY; P < 0.001). When extrapolating these findings to a commercial health plan with 1 million covered lives, the estimated total direct medical costs of T1D would be $103.4 million. CONCLUSIONS: This study showed that the total annual cost of managing an adult with T1D is significantly higher than that of an adult with T2D. Nondiabetes costs accounted for 40% of the total per-patient cost, similar to patients with T2D, confirming that as patients with T1D live longer lives, they may also be at greater risk for cardiometabolic complications. DISCLOSURES: This study was funded by Sanofi U.S. and Lexicon Pharmaceuticals as part of a business partnership in a diabetes program at the time this study was conducted. Joish and Davies are employees and stockholders of Lexicon Pharmaceuticals. Zhou, Preblick, and Paranjape are employees and stockholders of Sanofi. Lin was a postdoctoral fellow at Sanofi through Rutgers University during this project. Deshpande provided consulting services through Communication Symmetry. Verma is an employee of Evidera, which was contracted by Sanofi for work on this study. Pettus is a consultant for Diasome, Insulet, Lexicon, Lilly, Mannkind, Novo Nordisk, Sanofi, and Senseonics.

Burden of Cardiovascular Disease in Adult Patients with Type 1 Diabetes in the US.

BACKGROUND AND OBJECTIVES: The burden imposed by cardiovascular disease (CVD) on patients with type 1 diabetes (T1D) in the US has not been thoroughly addressed. In a retrospective observational analysis of the Optum® Clinformatics™ Data Mart database, the prevalence of CVD and cardiovascular risk factors (CVRF) as well as health economic outcomes were evaluated in adults with T1D. METHODS: Patients with at least one T1D medical claim between January 1, 2016, and December 31, 2016, were divided into cohorts based on the presence of CVD and/or CVRF. Descriptive and multivariate analyses enabled comparisons of healthcare resource utilization and costs between the cohorts. RESULTS: The analysis included 12,687 patients: CVD, 2871; CVRF, 5371; and no CVD/CVRF, 4445. The period prevalence of CVD and CVRF in the combined baseline and follow-up periods was 27% and 44%, respectively. Fewer patients in the no-CVD/CVRF cohort had a claim of a diabetes-related inpatient admission compared with the CVD cohort (8% vs. 26%, respectively; P < 0.001, standardized mean difference [SMD] > 0.1). Likewise, fewer patients with no CVD/CVRF visited the emergency department vs. those with CVRF or CVD (diabetes-related: 4% vs. 7% and 18%, respectively; P < 0.001, SMD > 0.1). Higher overall costs were observed for the CVD and CVRF vs. the no-CVD/CVRF cohort ($30,241 and $16,220, respectively, vs. $11,761; P < 0.05 and SMD ≥ 0.1 for both). CONCLUSIONS: Cardiovascular comorbidities are common among US adults with T1D. Considering their significant economic burden, optimal management is of the utmost importance to improve patient outcomes and reduce healthcare costs.

Differences between patients with type 1 diabetes with optimal and suboptimal glycaemic control: A real-world study of more than 30 000 patients in a US electronic health record database.

AIMS: To use electronic health record data from real-world clinical practice to assess demographics, clinical characteristics and disease burden of adults with type 1 diabetes (T1D) in the United States. MATERIALS AND METHODS: Retrospective observational study of adults with T1D for ≥24 months at their first visit with a T1D diagnosis code ("index date") between July 2014 and June 2016 in the Optum Humedica database. Demographic characteristics, acute complications (severe hypoglycaemia [SH], diabetic ketoacidosis [DKA]), microvascular complications, cardiovascular (CV) events and health care resource utilization during the 12 months before the index date ("baseline period") were compared between patients with optimal versus suboptimal glycaemic control (glycated haemoglobin [HbA1c] <7.0% vs. ≥7.0% [53 mmol/mol]) at the closest measurement to the index date. RESULTS: Of 31 430 adults with T1D, 79.9% had suboptimal glycaemic control (mean HbA1c 8.8% [73 mmol/mol]). These patients were more likely to be younger, African American, uninsured or on Medicaid, obese, smokers, have uncontrolled hypertension and have depression. Despite worse glycaemic control and increased CV risk factors of uncontrolled hypertension, obesity and smoking, rates of coronary heart disease and stroke were not higher in these patients. Patients with suboptimal glycaemic control also experienced more diabetes complications (including SH, DKA and microvascular disease) and utilized more emergency care, with more emergency department visits and inpatient stays. CONCLUSION: This real-world study of >30 000 adults with T1D showed that individuals with suboptimal versus optimal glycaemic control differed significantly in terms of health care coverage, comorbidities, diabetes-related complications, health care utilization and CV risk factors. However, suboptimal control was not associated with increased risk of CV outcomes.

Insights Into Patients' Experience With Type 1 Diabetes: Exit Interviews From Phase III Studies of Sotagliflozin.

PURPOSE: The purpose of this study was to conduct qualitative participant interviews to provide context to the meaningfulness of improvements in end points seen in 2 large-scale Phase III sotagliflozin trials in participants with type 1 diabetes. METHODS: Participants were eligible for an interview if they had exited one of the clinical trials within the previous 12 months. Participants were recruited by investigators at the clinical trial sites, and interviews were conducted by independent interviewers by telephone in accordance with a semistructured interview guide. Both interviewers and participants were blinded to treatment assignment. Qualitative analysis was conducted using ATLAS-ti version 7.5, and descriptive statistics were computed and summarized. FINDINGS: Across 3 countries, 41 participants were interviewed. Difficulty maintaining blood glucose within a desired range, described by participants as lack of blood glucose "stability," was the most concerning symptom that they reported, wanting to see it improved during the clinical trial because it negatively impacted their physical, mental, and emotional lives. Participants who reported symptom improvement also reported a positive psychosocial impact while taking the clinical trial medication. All participants who monitored ketones described themselves as being "pretty confident" to "very confident" that they could avoid diabetic ketoacidosis by monitoring both ketone levels and understanding the physical signs and symptoms of hyperglycemia. IMPLICATIONS: Improvements in glucose stability and control were important to participants with type 1 diabetes, as these improvements were correlated with improvements in the participants' lives. ClinicalTrials.gov identifiers: NCT02384941; NCT02421510.

Incidences of Severe Hypoglycemia and Diabetic Ketoacidosis and Prevalence of Microvascular Complications Stratified by Age and Glycemic Control in U.S. Adult Patients With Type 1 Diabetes: A Real-World Study.

OBJECTIVE: To assess the burden of disease for adults with type 1 diabetes in a U.S. electronic health record database by evaluating acute and microvascular complications stratified by age and glycemic control. RESEARCH DESIGN AND METHODS: This is a retrospective observational study of adults with type 1 diabetes (1 July 2014-30 June 2016) classified using a validated algorithm, with disease duration ≥24 months and, during a 12-month baseline period, not pregnant and having one or more insulin prescriptions and one or more HbA1c measurements. Demographic characteristics, acute complications (severe hypoglycemia [SH], diabetic ketoacidosis [DKA]), and microvascular complications (neuropathy, nephropathy, retinopathy) were stratified by age (18-25, 26-49, 50-64, ≥65 years) and glycemic control (HbA1c <7%, 7% to <9%, ≥9%). RESULTS: Of 31,430 patients, ∼20% had HbA1c <7%. Older patients had lower HbA1c values than younger patients (P < 0.001). Patients with poor glycemic control had the highest annual incidence of SH (4.2%, 4.0%, and 8.3%) and DKA (1.3%, 2.8%, and 15.8%) for HbA1c <7%, 7% to <9%, and ≥9% cohorts, respectively (both P < 0.001), and a higher prevalence of neuropathy and nephropathy (both P < 0.001). CONCLUSIONS: For adults with type 1 diabetes, glycemic control appears worse than previously estimated. Rates of all complications increased with increasing HbA1c. Compared with HbA1c <7%, HbA1c ≥9% was associated with twofold and 12-fold higher incidences of SH and DKA, respectively. Younger adults had more pronounced higher risks of SH and DKA associated with poor glycemic control than older adults.

Glycaemic goal attainment and hypoglycaemia outcomes in type 2 diabetes patients initiating insulin glargine 300 units/mL or 100 units/mL: Real-world results from the DELIVER Naïve cohort study.

AIMS: To compare HbA1c and hypoglycaemia in insulin-naïve patients with type 2 diabetes (T2D) who initiated insulin glargine 300 units/mL (Gla-300) or 100 units/mL (Gla-100). MATERIALS AND METHODS: This retrospective cohort study examined electronic medical records of insulin-naïve adults with T2D who initiated Gla-300 or Gla-100 during March 2015 through to December 2016 with active records for ≥12 months before and ≥6 months after initiation, and ≥1 valid HbA1c value during 6-month baseline and 90-180-day follow-up. Outcomes included HbA1c and hypoglycaemia. Cohorts were propensity score-matched (1:2) on baseline demographic and clinical characteristics. Sensitivity analyses were conducted using broader inclusion criteria. RESULTS: The matched cohorts included 1004 Gla-300 and 2008 Gla-100 initiators (mean age 60.4 years; 53.2% male). During 6-month follow-up, Gla-300 versus Gla-100 initiators had a greater mean HbA1c decrease (-1.52 ± 2.08% vs. -1.30 ± 2.12%; P = 0.003) and more patients achieved HbA1c <7% (25.0% vs. 21.5%; P = 0.029) and <8% (55.0% vs. 49.2%; P = 0.002); and HbA1c <7% (21.9% vs. 17.4%; P = 0.003) and <8% (49.1% vs. 41.8%; P < 0.001) without hypoglycaemia. Gla-300 initiators were similarly or less likely to have any or inpatient/emergency department-associated hypoglycaemia during 3- and 6-month follow-up (e.g. any hypoglycaemia to 6 months: 9.7% vs. 12.5%; adjusted odds ratio 0.61; P = 0.057). CONCLUSIONS: Among insulin-naïve adults with T2D, Gla-300 was associated with significantly better HbA1c reductions (latest value during 90-180-day follow-up) and similar or improved hypoglycaemia outcomes (3- and 6-month follow-up) than Gla-100.

Clinical outcomes in real-world patients with type 2 diabetes switching from first- to second-generation basal insulin analogues: Comparative effectiveness of insulin glargine 300 units/mL and insulin degludec in the DELIVER D+ cohort study.

AIMS: To compare clinical outcomes in patients with type 2 diabetes (T2D) switching from insulin glargine 100 units/mL (Gla-100) or insulin detemir (IDet) to insulin glargine 300 units/mL (Gla-300) or insulin degludec (IDeg). MATERIALS AND METHODS: We conducted a retrospective, observational study of electronic medical records for Gla-300/IDeg adult switchers (March 1, 2015 to January 31, 2017) with active records for 12-month baseline (glycated haemoglobin [HbA1c] used a 6-month baseline period) and 6-month follow-up periods. Gla-300 and IDeg switchers were propensity score-matched using baseline demographic and clinical characteristics. Outcomes were HbA1c change and goal attainment (among patients with HbA1c captured at follow-up), and hypoglycaemia with fixed follow-up (intention-to-treat [ITT]; 6 months) and variable follow-up (on-treatment [OT]; to discontinuation or 6 months). RESULTS: Each matched cohort comprised 1592 patients. The mean decrease in HbA1c and HbA1c goal (<7.0% [53 mmol/mol] and <8.0% [64 mmol/mol]) attainment rates were similar for Gla-300 (n = 742) and IDeg (n = 727) switchers. Using fixed follow-up (ITT method), hypoglycaemia incidence decreased significantly from baseline with Gla-300 (all hypoglycaemia: 15.6% to 12.7%; P = .006; hypoglycaemia associated with inpatient/emergency department [ED] encounter: 5.3% to 3.5%; P = .007), but not with IDeg. After adjusting for baseline hypoglycaemia, no significant differences in hypoglycaemia incidence and event rate were found at follow-up (ITT) for Gla-300 vs IDeg. Using variable follow-up (OT), hypoglycaemia incidence was similar in both groups, but Gla-300 switchers had a lower inpatient/ED hypoglycaemia event rate at follow-up (adjusted rate ratio 0.56; P = .016). CONCLUSIONS: In a real-world setting, switching from Gla-100 or IDet to Gla-300 or IDeg was associated with similar improvements in glycaemic control and hypoglycaemia in adult patients with T2D.

Treatment Dosing Patterns and Clinical Outcomes for Patients with Type 2 Diabetes Starting or Switching to Treatment with Insulin Glargine (300 Units per Milliliter) in a Real-World Setting: A Retrospective Observational Study.

INTRODUCTION: Usage patterns and effectiveness of a longer-acting formulation of insulin glargine at a strength of 300 units per milliliter (Gla-300) have not been studied in real-world clinical practice. This study evaluated differences in dosing and clinical outcomes before and after Gla-300 treatment initiation in patients with type 2 diabetes starting or switching to treatment with Gla-300 to assess whether the benefits observed in clinical trials translate into real-world settings. METHODS: This was a retrospective observational study using medical record data obtained by physician survey for patients starting treatment with insulin glargine at a strength of 100 units per milliliter (Gla-100) or Gla-300, or switching to treatment with Gla-300 from treatment with another basal insulin (BI). Differences in dosing and clinical outcomes before versus after treatment initiation or switching were examined by generalized linear mixed-effects models. RESULTS: Among insulin-naive patients starting BI treatment, no difference in the final titrated dose was observed in patients starting Gla-300 treatment versus those starting Gla-100 treatment [least-squares (LS) mean 0.43 units per kilogram vs 0.44 units per kilogram; P = 0.77]. Both groups had significant hemoglobin A1c level reductions (LS mean 1.21 percentage points for Gla-300 and 1.12 percentage points for Gla-100 ; both P < 0.001). The relative risk of hypoglycemic events after Gla-300 treatment initiation was lower than that after Gla-100 treatment initiation [0.31, 95% confidence interval (CI) 0.12-0.81; P = 0.018] at similar daily doses. The daily dose of BI was significantly lower after switching to treatment with Gla-300 from treatment with another BI (0.73 units per kilogram before switch vs 0.58 units per kilogram after switch; P = 0.02). The mean hemoglobin A1c level was significantly lower after switching than before switching (adjusted difference - 0.95 percentage points, 95% CI - 1.13 to - 0.78 percentage points ; P < 0.0001). Hypoglycemic events per patient-year were significantly lower (relative risk 0.17, 95% CI 0.11-0.26; P < 0.0001). CONCLUSIONS: Insulin-naive patients starting Gla-300 treatment had fewer hypoglycemic events, a similar hemoglobin A1c level reduction, and no difference in insulin dose versus patients starting Gla-100 treatment. Patients switching to Gla-300 treatment from treatment with other BIs had significantly lower daily doses of BI, with fewer hypoglycemic events, without compromise of hemoglobin A1c level reduction. These findings suggest Gla-300 in a real-world setting provides benefits in terms of dosing, with improved hemoglobin A1c level and hypoglycemia rates. FUNDING: Sanofi US Inc. (Bridgewater, NJ, USA).

Relationship between treatment persistence and A1C trends among patients with type 2 diabetes newly initiating basal insulin.

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla-100) or insulin detemir (DET) with ≥1 A1C measurement during 12-month baseline and 18-month follow-up periods were included. Patients with a refill gap of >90 days were considered non-persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow-up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non-persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.

Cost-effectiveness of edoxaban for the treatment of venous thromboembolism based on the Hokusai-VTE study.

OBJECTIVE: Venous thromboembolism (VTE) is associated with almost 300,000 deaths per year in the United States. Novel oral anticoagulants (NOACs) offer an alternative to warfarin-based therapy without monitoring requirements and with fewer drug and food interactions. Edoxaban, a direct Xa inhibitor, is approved by the Food and Drug Administration (FDA), based upon results of the Hokusai-VTE Phase 3 trial. The trial demonstrated that edoxaban administered once daily after initial treatment with heparin was non-inferior in reducing the risk of VTE recurrence and caused significantly less major and clinically relevant non-major (CRNM) bleeding compared to warfarin. The objective of this study was to evaluate the cost-effectiveness of edoxaban versus warfarin for the treatment of adults with VTE. METHODS: A cost-effectiveness model was developed using patient-level data from the Hokusai-VTE trial, clinical event costs from real-world databases, and drug acquisition costs for warfarin of $0.36 and edoxaban of $9.24 per tablet. RESULTS: From a U.S. health-care delivery system perspective, the incremental cost-effectiveness ratio (ICER) was $22,057 per quality adjusted life year (QALY) gained. Probabilistic sensitivity analysis showed that edoxaban had an ICER <$50,000 per QALY gained relative to warfarin in 67% of model simulations. The result was robust to variation in key model parameters including the cost and disutility of warfarin monitoring. CONCLUSION: Despite its higher drug acquisition cost, edoxaban is a cost-effective alternative to warfarin for the treatment of VTE.

Review of the cost of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is the second most common medical complication and a cause of excess length of hospital stay. Its incidence and economic burden are expected to increase as the population ages. We reviewed the recent literature to provide updated cost estimates on VTE management. METHODS: Literature search strategies were performed in PubMed, Embase, Cochrane Collaboration, Health Economic Evaluations Database, EconLit, and International Pharmaceutical Abstracts from 2003-2014. Additional studies were identified through searching bibliographies of related publications. RESULTS: Eighteen studies were identified and are summarized in this review; of these, 13 reported data from the USA, four from Europe, and one from Canada. Three main cost estimations were identified: cost per VTE hospitalization or per VTE readmission; cost for VTE management, usually reported annually or during a specific period; and annual all-cause costs in patients with VTE, which included the treatment of complications and comorbidities. Cost estimates per VTE hospitalization were generally similar across the US studies, with a trend toward an increase over time. Cost per pulmonary embolism hospitalization increased from $5,198-$6,928 in 2000 to $8,764 in 2010. Readmission for recurrent VTE was generally more costly than the initial index event admission. Annual health plan payments for services related to VTE also increased from $10,804-$16,644 during the 1998-2004 period to an estimated average of $15,123 for a VTE event from 2008 to 2011. Lower costs for VTE hospitalizations and annualized all-cause costs were estimated in European countries and Canada. CONCLUSION: Costs for VTE treatment are considerable and increasing faster than general inflation for medical care services, with hospitalization costs being the primary cost driver. Readmissions for VTE are generally more costly than the initial VTE admission. Further studies evaluating the economic impact of new treatment options such as the non-vitamin K antagonist oral anticoagulants on VTE treatment are warranted.

Economic burden of recurrent venous thromboembolism: analysis from a U.S. hospital perspective.

PURPOSE: An analysis of resource utilization and hospital costs associated with recurrent venous thromboembolism (VTE) is presented. METHODS: A retrospective cohort analysis was conducted using a large U.S. hospital database. Patients with VTE-related hospitalization events during the period January-December 2010 were identified; data collection extended for up to 12 months after the index event. Postdischarge hospital resource use and total costs were compared in cohorts of patients with and without recurrent VTE. Regression analysis was performed to compare hospital costs and length of stay (LOS) during initial and subsequent VTE encounters. RESULTS: Among the study population of 43,734 patients, 4% had postdischarge VTE-related events during the data collection period. The median and mean ± S.D. times to VTE recurrence were 48 days and 98 ± 106 days, respectively. Patients with recurrent VTE had more all-cause hospitalizations than those without recurrent VTE (mean ± S.D., 1.07 ± 0.96 versus 0.15 ± 0.53; p < 0.0001), more all-cause emergency room visits (mean ± S.D., 0.31 ± 0.66 versus 0.05 ± 0.31; p < 0.0001), and greater total costs (mean ± S.D., $28,353 ± $39,624 versus $17,712 ± $33,461; p < 0.0001). Relative to initial VTE admissions, admissions for recurrent VTE were, on average, associated with a 14% longer LOS (p = 0.0002) and a 22% higher total cost (p < 0.001). CONCLUSION: Patients with recurrent VTE used more hospital resources than those without recurrent VTE. Readmissions for VTE were significantly longer and more costly than index encounters.