Budget Impact Analysis of Intensification with iGlarLixi Compared to Alternative Treatment Strategies Among Patients with Type 2 Diabetes Mellitus
verfasst von:
Jennifer Ken-Opurum, Sistla S. S. Srinivas, Divya Jain, Tejaswinee Shah, Mihail Samnaliev, Terry Dex, Scott Charland, Andrew Revel, Ronald Preblick
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.
Key Summary Points
Clinical benefits of treating patients with type 2 diabetes mellitus (T2DM) with iGlarLixi were demonstrated in clinical trials and real-world evidence (RWE) studies; however, its cost impact on healthcare payers is unknown.
A budget impact model was developed from a US payer’s perspective over a 1-year time horizon among a hypothetical plan population of 1 million patients; in scenario analysis, patients with uncontrolled glycated hemoglobin (HbA1C) could intensify from a background therapy of 60 units or less of daily insulin or oral antidiabetic drugs (OADs) to iGlarLixi, insulin glargine (iGlar), rapid-acting insulin (RAI), or glucagon-like peptide 1 receptor agonists (GLP-1RA) (depending on background).
For patients treated with insulin or OADs in background, the incremental per member per month (PMPM) cost for iGlarLixi alone was $0.03 and $1.25, respectively.
Intensification with iGlarLixi was associated with reduced healthcare costs to payers.
Introduction
Diabetes is a lifelong chronic condition affecting more than 537 million adults worldwide, imposing a significant clinical and humanistic burden on patients, their families, and healthcare systems globally [1, 2]. In the USA, 37.3 million people (about 1 in 10) had diabetes in 2019, accounting for $327 billion in medical costs and lost work and wages [3]. The financial impact of diabetes care on payers is substantial and projected to grow in the future [1]. Furthermore, the growing population of older adults with diabetes puts an increasing strain on the Medicare budget and is representative of the larger challenges of unsustainable growth in US healthcare costs that drove the passage of the Inflation Reduction Act of 2022 [4].
Anzeige
As per the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Standards of Care (SOC) guidelines, first-line treatments for patients with T2DM include metformin, glucagon-like peptide 1 receptor agonists (GLP-1RA), and sodium–glucose cotransporter 2 inhibitors (SGLT2i) depending upon the goal of their therapy [5, 6]; however, evidence suggests the need for treatment intensification for patients with T2DM who fail to achieve target glycated hemoglobin (HbA1c) levels with basal insulin analogues within 6 months of initiating treatment. In addition, if treatment goals include cardiorenal risk reduction, glycemic control, or weight management, the 2023 SOC guidelines recommend treatments like GLP-1RA, gastric inhibitory peptide (GIP)/GLP-1RA, or SGLT2i as the first line of therapy contingent upon the evidence of the individual agents. For very high efficacy glycemic management, the ADA suggests the utilization of GLP-1RAs (e.g., semaglutide, high-dose dulaglutide) or insulin in combination with a GLP-1RA as a fixed- or free-ratio combination. Furthermore, for those unable to meet HbA1c targets and already on GLP-1RA, or GIP/GLP-1RA, the addition of basal insulin as a free- or fixed-ratio combination is also recommended [7]. Moreover, if the HbA1C remains above target, patients may switch to premix, neutral protamine Hagedorn (NPH) + rapid-acting insulin (RAI), or basal-bolus regimens [8]. To effectively manage T2DM, two additional therapeutic escalation methods suggested by the ADA include the addition of RAI or switching to a multiple daily premixed insulin regimen (intermediate insulin and short-acting insulin co-formulation) [9]. In contrast to the co-administration of individual agents, fixed-ratio combination (FRC) products have been developed to simplify treatment regimens into a single daily injection, thereby improving patient adherence and indicated as having very high efficacy for glycemic lowering by the ADA SOC guidelines [10]. The FRC of the long-acting basal insulin analogue insulin glargine 100 U/mL (iGlar) and the GLP-1RA lixisenatide (Lixi; together iGlarLixi) has been approved in the USA since 2016 as an adjunct to diet and exercise to improve glycemic control in individuals with T2DM [11].
The efficacy and safety profiles of iGlarLixi have previously been demonstrated in the LixiLan-L and LixiLan-O phase III, randomized, open-label, parallel-group trials, which included patients with T2DM who were not treated successfully on basal insulin or metformin alone at randomization, respectively. The LixiLan-L trial demonstrated that iGlarLixi was associated with a significant decrease in HbA1c compared to iGlar (− 0.5%; 95% confidence interval [− 0.6, − 0.4]; p < 0.001) without an increased risk of hypoglycemia in patients with T2DM [12]. Similarly, the LixiLan-O trial showed that iGlarLixi was more effective in achieving meaningful improvements in glycemic control without increase in weight or risk of hypoglycemia compared to iGlar [13].
Real-world studies have further provided evidence of the safety and effectiveness of iGlarLixi in patients with T2DM in routine clinical practice [14‐17]. However, there have been few economic evaluations of iGlarLixi in patients with T2DM to date. Recent cost-effectiveness study reports from the USA [18] and UK [19] revealed that iGlarLixi confers improved quality adjusted life years (QALYs) and lower costs compared to premix biphasic insulin aspart 30 (BIAsp) in people with suboptimal glycemic control on basal insulin. Additionally, total estimated costs were lowest for iGlarLixi compared with other fixed- and free-dose combinations of insulins plus GLP-1RA [20]. Similarly, the estimated annual acquisition cost associated with iGlarLixi was lowest when compared to alternatives [20]. According to another retrospective study, once daily iGlarLixi was an effective post-basal insulin treatment with longer treatment persistence and lower healthcare resource utilization than premixed insulin and basal-bolus insulin administration [14].
Although iGlarLixi was associated with better clinical efficacy (a significant decrease in HbA1c) and comparable safety profile (reduction in symptomatic hypoglycemia between insulin arms) than separate use of the GLP-1RA and the basal insulin [13, 21], the evidence generated from previous cost-effectiveness and budget impact analyses has not been conclusive for demonstrating the economic viability of iGlarLixi as a treatment option for patients with T2DM. Hence, this study aimed to evaluate the budget impact of treatment intensification with either iGlarLixi (Soliqua®), GLP-1RA, iGlar, or RAI, depending on oral antidiabetic drugs (OADs) or insulin background therapy, compared to the current treatment mix of these products among adult patients with T2DM.
Anzeige
Methods
Model Overview
The economic impact of two cohorts, patients uncontrolled on 60 units/day or less of insulin and patients uncontrolled on OADs as background treatments, was assessed using a budget impact model created in Microsoft Excel 2010 (Microsoft Corp, Redmond, WA). The insulin dose in background therapy was determined on the basis of clinical trials, where the maximum dose of iGlarLixi was 60 units/20 µg (60 units of insulin glargine and 20 µg of lixisenatide) [22‐24]. The budget impact was calculated as a difference between the costs of new and reference scenarios in which patients in both cohorts either switched to or added on respective intensification treatments, i.e., either GLP-1RA, iGlar, RAI, or iGlarLixi, depending on clinical guidelines. The model framework is presented in Fig. 1. Analysis was conducted among a hypothetical plan population of 1,000,000 over a time horizon of 1 year from a US healthcare payer perspective. Medication costs, dispensing costs, resource costs (needle, tests strip, and lancet), and cost benefits due to absolute reduction of HbA1c values while being on specific treatment compared to baseline HbA1c values were also included (diabetes-related drug costs, acute care costs, and diabetes-related outpatient costs) for computing the annual treatment costs. Additionally, co-payment, coinsurance, and inflation rates were applied to assess the actual costs of treatment. Monitoring costs for usage and administration of therapies were not included in the calculations.
Fig. 1
Budget impact model framework. GLP-1RA glucagon-like peptide 1 receptor agonists, HbA1c glycated hemoglobin, iGlar insulin glargine, iGlarLixi fixed-ratio combination of basal insulin glargine and lixisenatide, OAD oral antidiabetic drug, PMPM per member per month, RAI rapid-acting insulin, T2DM type 2 diabetes mellitus, BMI body mass index. Patients on metformin in background therapy could only add on intensification therapy and no switching was allowed, and patients on DPP4 in background therapy could not switch to iGlarLixi and GLP-1RA as treatment intensification options
×
The target population of adults diagnosed with and treated for T2DM was divided into patients on either insulin or OADs in background therapy, where the model index date was defined as the point of intensification (add-on or switch) with iGlarLixi/iGlar/GLP-1RA/RAI following the most recent uncontrolled HbA1c value while treated on their background therapy for at least 3 months. An incident-based modelling approach was employed, in which patients were included in analysis only if they were not previously treated with products considered as intensification therapy. Accordingly, total healthcare costs were calculated on an annual basis for all incident patients in the target population. Results were reported in 2022 US dollars (USD) for total annual costs of new and reference scenarios and budget impact per patient per month (PMPM).
Model Assumptions
According to 2022 ADA estimates, 90–95% of patients diagnosed with diabetes have T2DM [25]. The midpoint (92.5%) was used as the default value in the model. Other diabetes-related efficacies, events, or safety outcomes aside from HbA1c were not included in analysis. For the combination insulins/OADs, the unit costs were taken as the averages of the unit costs of each brand of insulin/OAD. The unit cost of GLP-1RA as a class was taken as an average of the unit costs of all individual GLP-1RAs. Patient cost-sharing (co-pay or coinsurance) was assumed to be paid once per refill frequency.
Model Inputs
A retrospective analysis of the Optum database was conducted among a population of patients with T2DM who met certain inclusion criteria, i.e., patients with at least one diagnosis of T2DM (International Classification of Diseases, 10th Revision [ICD-10] starting with E11 or International Classification of Diseases, 9th Revision [ICD-9] 250.00, 250.02, 250.10, 250.12, 250.20, 250.22, 250.30, 250.32, 250.40, 250.42, 250.50, 250.52, 250.60, 250.62, 250.70, 250.72, 250.80, 250.82, 250.90, 250.92) and had undergone treatment of T2DM either via insulins (basal insulin 60 units or less per day) or OADs between January 1, 2016 and March 31, 2022 (study period). Identified patients must also have had HbA1c values that were clinically relevant and feasible (5–13%), uncontrolled HbA1c values (≥ 7%), and had undertaken background therapy at least 3 months prior to uncontrolled HbA1c. Only patients who intensified with either iGlarLixi, RAI, GLP-1RA, or iGlar for the first time following the uncontrolled HbA1c reading were included. Patients had to also have been continuously enrolled in the health plan for at least 12 months prior to the index date, be at least 18 years of age, with a body mass index (BMI) between 10 and 40 kg/m2 pre-index, and not be pregnant (specific to female patients). An upper limit of 40 kg/m2 was set for BMI as bariatric surgery becomes a treatment option for these patients; thus, accounting for pharmacological treatment only would not adequately capture the clinical complexity of such cases [26]. Likewise, 15.5% of patients with T2DM are estimated to have BMI ≥ 40 kg/m2 [26, 27], so their exclusion from analysis would not majorly impact model results.
The proportion of patients coming from a background therapy of insulin or OADs (the insulin and OAD cohorts, respectively) and intensifying to respective treatments were based on the inclusion criteria specified above and are depicted in the consort diagram (Fig. 2). The list of background therapies and possible treatment intensifications for both cohorts are presented in Tables 1 and 2, respectively. Additionally, the average HbA1c reductions due to iGlarLixi/iGlar/ GLP-1RA were captured from the literature for both insulin [28] and OAD [29] cohorts.
Fig. 2
Real-world analysis consort diagram. BMI body mass index, GLP-1RA glucagon-like peptide 1 receptor agonists, HbA1c glycated hemoglobin, iGlar insulin glargine, iGlarLixi fixed-ratio combination of basal insulin glargine and lixisenatide, NPH neutral protamine Hagedorn, OAD oral antidiabetic drug, RAI rapid-acting insulin, T2DM type 2 diabetes mellitus
GLP-1RA glucagon-like peptide 1 receptor agonists, iGlar insulin glargine, iGlarLixi fixed-ratio combination of basal insulin glargine and lixisenatide, OAD oral antidiabetic drug, RAI rapid-acting insulin
×
The unit costs for the drugs were the wholesale acquisition costs (WAC), obtained from data on file (Table 3) [30]. The cost of dispensing was assumed to be the same for all the treatment arms, i.e., $13.85 (adjusted to 2022 USD) [31]. The model also included the annual diabetes-related cost savings of $629.53 (adjusting to 2022 USD) for every 1-percentage point reduction in HbA1c among patients with an index HbA1c ≥ 7% [32].
Data for insulin units per day was also retrieved from the retrospective database analysis. The units of all insulins and iGlarLixi were assumed to be 1500 U, whereas the prescription units of all OADs were assumed to be 90 tablets (1 tablet per day) over a 3-month prescription period. The prescription units of GLP-1RA as a class were 42.75 mg based on an average of units prescribed for individual GLP-1RA regimen drugs. GLP-1RA as a class comprised Bydureon® (AstraZeneca group of companies), Ozempic® (Novo Nordisk), Trulicity® (Eli Lilly and Company), Byetta® (AstraZeneca group of companies), Victoza® (Novo Nordisk), Adlyxin® (Sanofi‐Aventis US LLC), and Rybelsus® (Novo Nordisk).
The inputs for co-payment and coinsurance were obtained from Kaiser’s employer health benefits 2022 annual survey based on each drug’s tier placement [33]. Tier placement for the branded drugs was tier 2, while for generic/unbranded drugs it was tier 1.
Anzeige
The costs of test strips, lancets, and needles were included for insulins and GLP-1RA [34‐36]. The number of these resources consumed per day was based on the package inserts for these drugs.
Scenarios
To evaluate the effect of alternative intensifying market share proportions on healthcare budgets, hypothetical scenarios were analyzed. Table 4 lists the scenarios for the insulin and OAD cohorts.
Table 4
Description for alternative scenarios
Insulin cohort
1
Assuming maximum clinically plausible market intensification for iGlarLixi (switchers 6%)
2
Assuming equal market intensification for iGlarLixi (switchers 1.69%) and GLP-1RA (add-on 1.69%)
3
Assuming equal market intensification for iGlarLixi (switchers 1.69%) and RAI (add-on 1.69%)
OAD cohort
1
Assuming maximum clinically plausible market intensification for iGlarLixi (switchers and add-on both 6%)
2
Assuming equal market intensification for iGlarLixi and GLP-1RA (switchers 0.39% and add-on 0.35%)
3
Assuming equal market intensification for iGlarLixi and iGlar (switchers 0.39% and add-on 0.35%)
GLP-1RA glucagon-like peptide 1 receptor agonists, iGlar insulin glargine, iGlarLixi fixed-ratio combination of basal insulin glargine and lixisenatide, OAD oral antidiabetic drug, RAI rapid-acting insulin
Sensitivity Analysis
To investigate the impact of individual parameters on model results, one-way sensitivity analyses (OWSA) were conducted. All parameters were varied by ± 10% of the base case. Analysis was conducted separately for the insulin and OAD cohorts. Variables included in the OWSA were population inputs, baseline HbA1c, dosage, costs, costs related to HbA1c reductions, co-payment, and coinsurance.
Ethical Approval
The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Internal review board approval was not sought, as all analyses were applied to anonymized retrospective patient data. The electronic health record datasets analyzed during the current study are licensed by Sanofi from Optum, and permission to access and use data not publicly available from Optum was obtained.
Anzeige
Results
On the basis of proportions of patients observed in real-world data (RWD), an estimated target population of 57,131 patients with T2DM was modelled in this analysis to evaluate the economic impact of treatment intensification among those uncontrolled on a background therapy of 60 units/day or less of insulin (n = 9780) or OADs only (n = 47,350).
Insulin Cohort Results
Base Case
The total annual costs among the insulin cohort for iGlarLixi, GLP-1RA, and RAI were $409,990, $866,417,959, and $57,760,903, respectively, including the annual cost benefit from an absolute HbA1c reduction following treatment intensification. Treatment intensification had an incremental total budget impact of $897,556,502, while the incremental PMPM cost was $74.80 among the insulin cohort. The incremental PMPM cost for iGlarLixi alone was $0.03, the lowest among intensifying drugs, while PMPM costs for GLP-1RA and RAI were $72.20 and $4.81, respectively. Results are shown in Table 5 and Fig. 3.
Table 5
Base case results for insulin cohort (PMPM costs, $)
Treatments
Base scenario (PMPM)
New scenario (PMPM)
Budget impact (PMPM)
iGlarLixi
$0.00
$0.03
$0.03
GLP-1RA
$0.00
$72.20
$72.20
RAI
$0.06
$4.88
$4.81
Total
$2.32
$77.11
$74.80
A positive value in the table implies positive budget impact, i.e., additional costs rather than cost savings
GLP-1RA glucagon-like peptide 1 receptor agonists, iGlarLixi fixed-ratio combination of basal insulin glargine and lixisenatide, PMPM per member per month, RAI rapid-acting insulin
Fig. 3
Result graph for insulin cohort (PMPM costs, $). GLP-1RA glucagon-like peptide 1 receptor agonists, iGlarLixi fixed-ratio combination of basal insulin glargine and lixisenatide, PMPM per member per month, RAI rapid-acting insulin
×
Scenarios
Scenario 1: Assuming Maximum Clinically Plausible Market Intensification for iGlarLixi (6%)
When the market intensification for iGlarLixi was changed to 6% as compared to base case of 1.69%, and the remaining patients were proportionally intensified to GLP-1RA and RAI, the incremental PMPM costs for iGlarLixi changed from $0.03 to $0.12 and the incremental PMPM cost for the entire treatment-mix decreased from $74.80 to $71.50.
Scenario 2: Assuming Equal Market Intensification for iGlarLixi and GLP-1RA (1.69%)
When the market intensification percentage for GLP-1RA was assumed equal to iGlarLixi in the new scenario (1.69%) and the remaining patients intensified to RAI, the incremental PMPM costs for GLP-1RA were $2.28 and for iGlarLixi were $0.03. The incremental PMPM cost for the entire treatment-mix decreased from $74.80 to $10.50.
Scenario 3: Assuming Equal Market Intensification for iGlarLixi and RAI (1.69%)
When the market intensification percentage for RAI was assumed equal to iGlarLixi in the new scenario (1.69%) and the remaining patients intensified to GLP-1RA, the incremental PMPM costs for RAI were $0.11 and for iGlarLixi were $0.03. The incremental PMPM cost for the entire treatment-mix increased from $74.80 to $128.53.
One-Way Sensitivity Analysis (OWSA)
In OWSA, the proportion of patients uncontrolled on insulin was the most influential parameter affecting the base results, ranging the PMPM costs from $67.32 to $82.28, followed by the proportion of patients with T2DM (lower bound $67.32, upper bound $80.86) and units per day for NPH (lower bound $74.47, upper bound $75.12). Table 6 lists the top 10 parameters influencing the results, along with their lower and upper bounds, which is also depicted in Fig. 4.
Table 6
OWSA results for insulin cohort
Parameters
Base case
Lower bound
Upper bound
PMPM lower bound
PMPM upper bound
Patients uncontrolled on insulin
17.12%
15.41%
18.83%
$67.32
$82.28
Patients with type 2 diabetes
92.50%
83.25%
100.00%
$67.32
$80.86
Units per day—NPH
84.41
75.96
92.85
$74.47
$75.12
Units cost of—NPH
$0.28
$0.26
$0.31
$74.47
$75.12
Units cost of—RAI
$0.25
$0.22
$0.27
$74.62
$74.97
Units per day—RAI
52.73
47.46
58.00
$74.63
$74.96
Baseline HbA1c of selected population
9.06%
8.15%
9.96%
$74.83
$74.77
Annual cost benefit of 1% HbA1c reduction
$629.53
566.58
692.48
$74.83
$74.77
Dispensing fees of—NPH
$13.85
$12.46
$15.23
$74.79
$74.81
Dispensing fees of—RAI
$13.85
$12.46
$15.23
$74.79
$74.80
HbA1c glycated hemoglobin, NPH neutral protamine Hagedorn, PMPM per member per month, RAI rapid-acting insulin
The total annual costs among the OAD cohort for iGlarLixi, GLP-1RA, and iGlar were $14,985,743, $3,859,837,508, and $1,377,813,031, respectively, including the annual cost benefit from an absolute HbA1c reduction following treatment intensification. Treatment intensification had an incremental total budget impact of $238,170,096 while the incremental PMPM cost was $19.85 among the OAD cohort. The incremental PMPM cost for intensification with iGlarLixi was $1.25, the lowest among intensifying drugs, while the PMPM costs for intensification with GLP-1RA and iGlar were $321.65 and $114.82, respectively. Results are shown in Table 7 and Fig. 5.
Table 7
Base case results for OAD cohort (PMPM costs, $)
Treatments
Base scenario (PMPM)
New scenario (PMPM)
Budget impact (PMPM)
iGlarLixi
$0.00
$1.25
$1.25
GLP-1RA
$0.00
$321.65
$321.65
iGlar
$0.00
$114.82
$114.82
Total
$433.86
$453.71
$19.85
A positive value in the table implies positive budget impact, i.e., additional costs rather than cost savings
GLP-1RA glucagon-like peptide 1 receptor agonists, iGlar insulin glargine, iGlarLixi fixed-ratio combination of basal insulin glargine and lixisenatide, PMPM per member per month
Fig. 5
Result graph for OAD cohort (PMPM costs, $). GLP-1RA glucagon-like peptide 1 receptor agonists, iGlar insulin glargine, iGlarLixi Fixed-ratio combination of basal insulin glargine and lixisenatide, PMPM Per member per month
×
Scenarios
Scenario 1: Assuming Maximum Clinically Plausible Market Intensification (Switchers/Add-On) for iGlarLixi (6% Each)
When the market intensification for iGlarLixi (switchers and add-on) was changed to 6% from the base case of 0.39% and 0.35% for switchers and add-on, respectively, and the remaining patients were proportionally redistributed to other treatment intensification drugs, the incremental PMPM cost for iGlarLixi changed from $1.25 to $21.43, while the incremental PMPM cost for the entire treatment-mix decreased from $19.85 to − $33.80.
Scenario 2: Assuming Equal Market Intensification for iGlarLixi (Switchers and Add-On) and GLP-1RA (Switchers 0.39%, Add-On 0.35%)
When the market intensification percentage for GLP-1RA was assumed equal to iGlarLixi in the new scenario (i.e., 0.39% switchers and 0.35% add-on) and the remaining patients intensified to iGlar, the incremental PMPM cost for GLP-1RA was − $146.93, while the incremental PMPM cost for iGlarLixi was $1.25. The incremental PMPM cost for the entire treatment-mix decreased from $19.85 to − $319.08.
Scenario 3: Assuming Equal Market Intensification for iGlarLixi (Switchers and Add-On) and iGlar (Switchers 0.39%, Add-On 0.35%)
When market intensification percentage for iGlar was assumed equal to iGlarLixi in the new scenario (i.e., 0.39% switchers and 0.35% add-on) and the remaining patients intensified to GLP-1RA, the incremental PMPM cost for iGlar was $1.63, while the incremental PMPM cost for iGlarLixi was $1.25. The incremental PMPM cost for the entire treatment-mix increased from $19.85 to $241.56.
One-Way Sensitivity Analysis (OWSA)
In OWSA, units per day for multipill oral therapy combination was the most influential parameter affecting the base results, ranging the PMPM costs from $40.79 to − $1.10, followed by unit cost of multipill oral therapy combination (lower bound $40.75, upper bound − $1.06), and units per day for SGLT2i (lower bound $23.26, upper bound $16.44). Table 8 lists the top 10 parameters influencing the results, along with their lower and upper bounds, which is also depicted in Fig. 6.
Table 8
OWSA results for OAD cohort
Parameters
Base case
Lower bound
Upper bound
PMPM lower bound
PMPM upper bound
Units per day—combinations—multipill oral therapy
43.97
39.58
48.37
$40.79
− $1.10
Units cost of—combinations—multipill oral therapy
$15.57
$14.01
$17.12
$40.75
− $1.06
Units per day—SGLT2i
80.83
72.75
88.92
$23.26
$16.44
Units cost of—SGLT2i
$14.98
$13.48
$16.48
$23.25
$16.44
Patients uncontrolled on OADs
82.88%
74.59%
91.17%
$17.86
$21.83
Patients with type 2 diabetes
92.50%
83.25%
100.00%
$17.86
$21.46
Units per day—DPP4
18.33
16.50
20.17
$20.77
$18.93
Units cost of—DPP4
$16.39
$14.75
$18.03
$20.76
$18.93
Units cost of—iGlar
$0.28
$0.25
$0.31
$19.15
$20.54
Units per day—iGlar
43.77
39.39
48.15
$19.19
$20.50
DPP4 dipeptidyl peptidase 4, iGlar insulin glargine, OAD oral antidiabetic drug, PMPM per member per month, SGLT2 sodium-glucose cotransporter 2 inhibitor
Healthcare costs associated with diabetes treatment in the USA continue to increase. Hence, there is a pressing need for accurate and relevant assessment of the cost and affordability of adopting new antidiabetic medications. This study used a budget impact model applied to two cohorts of patients with T2DM uncontrolled on a background therapy of either 60 units or less of insulin daily or OADs, who either switched to or added on clinically plausible intensification treatment options, including GLP-1RA, iGlar, RAI, or iGlarLixi. We found that switching to or adding on iGlarLixi was associated with lower PMPM costs to payers compared to alternative intensification therapies.
Anzeige
For both insulin and OAD cohorts, iGlarLixi represented lower annual treatment costs compared to other intensification drugs. Furthermore, our results demonstrated that the PMPM costs for iGlarLixi were much lower than that for GLP-1RA/RAI/iGlar based on the proportion of intensification determined by RWD analysis. Results were primarily influenced by two factors: (1) GLP-1RA had relatively higher unit costs ($270.77) in comparison to iGlarLixi ($0.57) and all other drugs (< $0.50); and (2) iGlarLixi’s annual cost savings from an absolute reduction in HbA1c (insulin cohort $791.14 and OAD cohort $1,078.89) were higher than the cost savings associated with the same for GLP-1RA (insulin cohort $642.12 and OAD cohort $642.12). Therefore, in the context of treatment decisions made according to economic factors, iGlarLixi was shown to be the less expensive treatment option than other products in the model.
Directional findings for the two cohorts were similar; however, the extent of overall budget impacts varied. This was mostly due to the OAD cohort’s larger starting sample size (n = 47,350) and resulting higher percentage of patients initiating background treatment when compared to the insulin cohort (n = 9780). For both the cohorts, scenario analysis revealed that the PMPM costs for iGlarLixi were either the same or increased. For most scenarios, the overall budget impact reduced for the entire treatment mix. This was because the cost increase for iGlarLixi was smaller than the cost decrease for other intensification treatment options, which had higher unit costs. The overall incremental PMPM costs were higher than the base case for both cohorts, whereas the higher proportion of patients intensified to GLP-1RA. This was because of the higher unit costs of GLP-1RA along with smaller cost savings in terms of absolute HbA1c reductions. To summarize, the findings of the scenario analysis suggest that the overall financial burden related to therapeutic selection for managing diabetes may be expected to decrease if more patients switch to or add on iGlarLixi.
There is a lack of studies across the literature to demonstrate the budget impact of iGlarLixi. The current budget impact analysis intended to fill the gap by evaluating the economic impact of treatment intensification with iGlarLixi and other intensifying drugs in patients with T2DM. The findings of our study are consistent with previously conducted cost-effectiveness analyses. Our results are aligned with a recent cost-effectiveness analysis in the UK in which iGlarLixi offered comparable clinical efficacy but at a substantial cost reduction compared to other fixed- and free-ratio combinations of insulins plus GLP-1RA alternative [20]. The use of iGlarLixi was associated with significant cost savings and favorable utility outcomes in patients with T2DM with insufficient glycemic control despite using GLP-1RAs. In another cost-effectiveness analysis conducted in the USA comparing iGlarLixi to BIAsp 30 in patients with T2DM suboptimally controlled with basal insulin, iGlarLixi had lower costs and demonstrated an increase in QALYs, results which were primarily driven by cost reductions associated with iGlarLixi compared to the greater dose and twice-daily administration of BIAsp 30 [18]. In addition, iGlarLixi was associated with a lower incidence of hypoglycemia compared to premixed insulin, resulting in slightly more QALYs gained in patients with T2DM. This finding was further supported by a cost-effectiveness study from South Korea, where iGlarLixi demonstrated acceptable incremental cost-effectiveness over premixed insulin and was shown to be a cost-effective treatment option for patients with T2DM [37]. The results of our current model were also consistent with the LixiLan-L and LixiLan-O trials, which demonstrated the superior efficacy of iGlarLixi to achieve meaningful HbA1c reductions [12, 13]. Moreover, our analysis highlighted significant cost savings associated with absolute reduction in HbA1c for iGlarLixi compared to alternative intensification therapies.
Similarly, a study in the UK showed that treatment acquisition was the main driver of cost differences between premix BIAsp 30 and iGlarLixi, making the latter a simple, cost-effective option for intensification [19]. Another study in the USA compared the healthcare resource utilization and costs for iGlarLixi with newly initiated free-dose combinations of basal insulin and GLP-1RA that were started either simultaneously or sequentially [18]. The results showed that iGlarLixi was associated with longer persistence and better adherence, fewer diabetes-related pharmacy visits, and lower diabetes medication costs. A budget impact study of iGlarLixi in the treatment of T2DM in the Guatemalan Social Security Institute showed that the inclusion of iGlarLixi for the treatment of T2DM would result in budget savings considering its associated health benefits [38].
Across the literature, the majority of studies did not perform sensitivity analysis. In the present study, findings from OWSA suggest that the largest impact on annual treatment costs was due to the variation in unit costs of iGlarLixi, followed by annual treatment costs of GLP-1RA. The results of OWSA for the insulin cohort showed that the most influential parameter affecting the base result was the number of patients with T2DM, followed by units per day for NPH and unit cost of NPH. Similarly, for the OAD cohort, the most influential parameters were units per day for dipeptidyl peptidase 4 (DPP4), followed by the unit cost of DPP4 and the number of patients uncontrolled on OADs.
The strengths of this study included analysis of two cohorts of patients identified in RWD who would be clinically eligible to intensify to respective treatment options, budget impact analysis pertaining to intensification strategies implemented in the Lixilan-L and -O trials, selection of model inputs from a variety of sources including administrative claims, the literature, data on file, and clinical opinion, and use of a contemporary cohort of patients whose costs were inflated to the most up to date values at the time of analysis. However, several limitations remain. As we followed protocol design of the Lixilan-L and -O clinical trials, any treatments not included therein were likewise excluded from the model. Although HbA1c is a reliable measure of chronic glycemia, the cost savings associated with HbA1c were fixed in the model regardless of the patient’s current HbA1c value. Moreover, the current model did not consider the safety outcomes associated with treatment. The optimal management of T2DM should consider not only the efficacy of antidiabetic drugs in lowering blood sugar levels but also cardiovascular safety and other long-term diabetes complications [39]. Another limitation was the use of publicly available estimates rather than inputs derived directly from patient-level data for some of the cost parameters, including needles, lancets, and test strips. In addition, we did not conduct indirect treatment comparisons via network meta-analysis, e.g., a comprehensive rebate analysis to explore discounts necessary for new interventions to show cost parity with competitors.
Conclusions
The model demonstrates that treatment intensification with iGlarLixi can be a cost-saving alternative compared to other intensification treatment options for patients with T2DM. Switching to or adding on iGlarLixi to background treatments was the less expensive treatment option, effectively reducing healthcare costs to payers. This study provides important insight into the economic impact of iGlarLixi on payers and patients who frequently bear out-of-pocket expenses associated with diabetes care. The result of this budget impact analysis can be used to inform analyses regarding selection of affordable therapeutic options for diabetes management, such as iGlarLixi.
Acknowledgements
Medical Writing and Editorial Assistance
Medical Writing and editorial support were provided by Pratikshya Ray, PhD, in accordance with Good Publication Practice Guidelines [40] and funded by Sanofi US.
Authorship
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Declarations
Conflict of Interest
The authors Jennifer Ken-Opurum, Sistla S.S. Srinivas, Divya Jain, Tejaswinee Shah, Mihail Samnaliev, Terry Dex, Scott Charland, Andrew Revel, and Ronald Preblick declare that they have no competing interests aside from those listed above. Mihail Samnaliev was employed at Axtria during the conduct of this study, and is now employed at Stratevi. Scott Charland was employed at Sanofi during the conduct of this study, and is now retired.
Ethical Approval
The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Internal review board approval was not sought, as all analyses were applied to anonymized retrospective patient data. The electronic health record datasets analyzed during the current study are licensed by Sanofi from Optum, and permission to access and use data not publicly available from Optum was obtained.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.
Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.
Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.
„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.
Update Innere Medizin
Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.
