Evaluation of the long-term cost-effectiveness of IDegLira versus liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the USA

Background and aims: IDegLira, a fixed ratio combination of insulin degludec and glucagon-like peptide-1 receptor agonist liraglutide, utilizes the complementary mechanisms of action of these two agents to improve glycemic control with low risk of hypoglycemia and avoidance of weight gain. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira vs liraglutide added to basal insulin, for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US setting.

Methods: Projections of lifetime costs and clinical outcomes were made using the IMS CORE Diabetes Model. Treatment effect data for patients receiving IDegLira and liraglutide added to basal insulin were modeled based on the outcomes of a published indirect comparison, as no head-to-head clinical trial data is currently available. Costs were accounted in 2015?US dollars ($) from a healthcare payer perspective.

Results: IDegLira was associated with small improvements in quality-adjusted life expectancy compared with liraglutide added to basal insulin (8.94 vs 8.91 discounted quality-adjusted life years [QALYs]). The key driver of improved clinical outcomes was the greater reduction in glycated hemoglobin associated with IDegLira. IDegLira was associated with mean costs savings of $17,687 over patient lifetimes vs liraglutide added to basal insulin, resulting from lower treatment costs and cost savings as a result of complications avoided.

Conclusions: The present long-term modeling analysis found that IDegLira was dominant vs liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the US, improving clinical outcomes and reducing direct costs.     

Evaluating the short-term cost-effectiveness of liraglutide versus lixisenatide in patients with type 2 diabetes in the United States

Aims: Bringing patients with type 2 diabetes to recommended glycated hemoglobin (HbA1c) treatment targets can reduce the risk of developing diabetes-related complications. The aim of the present analysis was to evaluate the short-term cost-effectiveness of once-daily liraglutide 1.8?mg vs once-daily lixisenatide 20?μg as an add-on to metformin for treatment of type 2 diabetes in the US by assessing the cost per patient achieving HbA1c-focused and composite treatment targets.

Materials and methods: Percentages of patients achieving recommended targets were obtained from the LIRA-LIXI trial, which compared the efficacy and safety of once-daily liraglutide 1.8?mg and once-daily lixisenatide 20?μg as an add-on to metformin in patients with type 2 diabetes failing to achieve glycemic control with metformin. Annual costs were estimated from a healthcare payer perspective. An economic model was developed to evaluate the annual cost per patient achieving target (cost of control) with liraglutide 1.8?mg vs lixisenatide 20?μg for five end-points.

Results: Annual treatment costs were higher with liraglutide 1.8?mg than lixisenatide 20?μg, but this was offset by greater clinical efficacy, and the cost of control was lower with liraglutide 1.8?mg than lixisenatide 20?μg for all five end-points. The annual cost of control was USD 3,850, USD 11,404, USD 3,807, USD 4,299, and USD 6,901 lower for liraglutide 1.8?mg than lixisenatide 20?μg for targets of HbA1c?Conclusions: Once-daily liraglutide 1.8?mg was associated with greater clinical efficacy than once-daily lixisenatide 20?μg, which resulted in a lower annual cost of control for HbA1c-focused and composite treatment targets.     

A short-term cost-utility analysis of insulin degludec versus insulin glargine U100 in patients with type 1 or type 2 diabetes in Denmark

Background and aims: Insulin degludec is an insulin analog with an ultra-long duration of action that exhibits less intra-patient variability in its glucose-lowering activity, and reduces nocturnal, overall, and severe hypoglycemia relative to insulin glargine. The aim of the present study was to evaluate the cost-effectiveness of insulin degludec relative to insulin glargine in patients with: type 1 diabetes (T1D), type 2 diabetes receiving basal-only therapy (T2DBOT), and type 2 diabetes receiving basal-bolus therapy (T2DBB) in Denmark.

Methods: A short-term (1 year) cost-utility model was developed to model insulin use, non-severe and severe hypoglycemia, and self-monitoring of blood glucose in patients using insulin degludec and insulin glargine from the perspective of a Danish healthcare payer. Where possible, data were derived from Danish patients with diabetes and meta-analyses of clinical trials comparing insulin degludec with insulin glargine. Using these characteristics, the model estimated costs and quality-adjusted life years (QALYs) gained for the two insulin regimens in each of the three diabetes populations.

Results: Insulin degludec dominated insulin glargine (i.e. reduced costs while improving quality-adjusted life expectancy) in patients with T1D and patients with type 2 diabetes using a basal-only insulin regimen. In the T2DBB cohort, insulin degludec was associated with an incremental cost-effectiveness ratio of DKK 221,063 per QALY gained, which would be considered cost-effective at a willingness-to-pay threshold of EUR 30,000 (～DKK 224,000) per QALY gained. Sensitivity analysis showed that results were most affected by changes in hypoglycemia rate ratio assumptions, but were broadly insensitive to changes in individual input parameters.

Conclusions: Insulin degludec reduces incidence of hypoglycemia and improves quality-of-life in patients with diabetes. Over a 1-year time horizon, insulin degludec resulted in cost savings relative to insulin glargine in T1D and T2DBOT cohorts, while being cost-effective in T2DBB.     

Insulin degludec versus insulin glargine U100 for patients with type 1 or type 2 diabetes in the US: a budget impact analysis with rebate tables

Background and aims: Drug rebates are almost universally negotiated privately between the manufacturer and the payer in the US. The aim of the present study was to illustrate the use of a “rebate table” to improve the transparency and utility of published budget impact analyses in the US by modeling ranges of hypothetical rebates for two comparators. Worked examples were conducted to illustrate the budgetary implications of using insulin degludec (IDeg) relative to insulin glargine (IGlar) U100 in patients with type 1 or 2 diabetes.

Methods: A short-term (1-year) budget impact model was developed to evaluate the costs of switching to IDeg from IGlar in patients with type 1 or 2 diabetes on basal-bolus and basal-only insulin, respectively. The analysis used insulin dose and hypoglycemia data from recent randomized trials, data on the prevalence of diabetes, and estimates of the proportion of patients using each insulin regimen. The model was configured to run multiple rebate scenarios to generate a rebate table in a hypothetical 1 million member commercial plan.

Results: Relative to IGlar, IDeg resulted in reductions in non-severe and severe hypoglycemia incidence and costs both in patients with type 1 and patients with type 2 diabetes. Insulin acquisition costs were higher, and respective rebates of 7.3% and 10.6% were required for IDeg to break-even with IGlar at the full list price. Incremental per member per month IDeg costs without a rebate were USD 0.04 in type 1 diabetes and USD 0.80 in type 2 diabetes.

Conclusions: Using IDeg instead of IGlar at list price could result in a modest increase in costs when considering insulin and hypoglycemia costs alone, but modest incremental rebates with IDeg would result in cost neutrality relative to IGlar. In addition, IDeg would result in reduced incidence of severe and non-severe hypoglycemia.     

Therapy conversion to biphasic insulin aspart 30 improves long-term outcomes and reduces the costs of type 2 diabetes in Saudi Arabia

Objective: An observational study in Saudi Arabia indicated that conversion to biphasic insulin aspart 30 (BIAsp 30) from human insulin (HI) was associated with improvement of glycaemic control.

Methods: A validated computer simulation model of diabetes was used to project long-term outcomes (such as quality-adjusted life expectancy and direct medical costs) based on patient characteristics and treatment effects observed in the Saudi Arabian PRESENT subgroup (n=598). Baseline prevalence of comorbidities was obtained from published sources. Primary research was performed in Riyadh and Jeddah to derive diabetes-related complication costs and patient management practices.

Results: Conversion to BIAsp 30 from HI was projected to increase life expectancy by 0.62 years (11.77 ± 0.20 vs. 11.15 ± 0.19 years) and quality-adjusted life expectancy by 0.96 quality-adjusted life years (QALYs) (7.03 ± 0.12 vs. 6.07 ± 0.11 QALYs). Direct medical cost savings of Saudi Arabian Riyals (SAR) 53,879 per patient were projected for conversion to BIAsp 30 therapy (SAR 84,761 ± 3102 vs. SAR 138,640 ± 4102 per patient). Cost savings were driven by lower costs of hypoglycaemia (SAR 286 vs. SAR 57,437 per patient), and lower costs of renal complications (SAR 18,848 vs. SAR 31,228) over patient lifetimes.

Conclusion: Conversion to BIAsp 30 from HI was projected to improve life expectancy and quality-adjusted life expectancy while reducing lifetime direct medical costs.     

An analysis of the cost-effectiveness of switching from biphasic human insulin 30, insulin glargine,or neutral protamine Hagedorn to biphasic insulin aspart 30 in people with type 2 diabetes

Abstract

Aims:

The aim of this analysis was to assess the cost-effectiveness of switching from biphasic human insulin 30 (BHI), insulin glargine (IGlar), or neutral protamine Hagedorn (NPH) insulin (all?±?oral glucose-lowering drugs [OGLDs]) to biphasic insulin aspart 30 (BIAsp 30) in people with type 2 diabetes in India, Indonesia, and Saudi Arabia.

Methods:

The IMS CORE Diabetes Model was used to determine the clinical outcome, costs, and cost-effectiveness of switching from treatment with BHI, IGlar, or NPH to BIAsp 30 over a 30-year time horizon. A 1-year analysis was also performed based on quality-of-life data and treatment costs. Incremental cost-effectiveness ratios (ICERs) were expressed as a fraction of gross domestic product (GDP) per capita, and cost-effectiveness was defined as ICER <3-times GDP per capita.

Results:

Switching treatment from BHI, IGlar, or NPH to BIAsp 30 was associated with an increase in life expectancy of >0.7 years, reduction in all diabetes-related complications, and was considered as cost-effective or highly cost-effective in India, Indonesia, and Saudi Arabia (BHI to BIAsp 30, 0.26 in India, 1.25 in Indonesia, 0.01 in Saudi Arabia; IGlar to BIAsp 30, ?0.68 in India, ?0.21 in Saudi Arabia; NPH to BIAsp 30, 0.15 in India, ?0.07 in Saudi Arabia; GDP per head per annum/quality-adjusted life-year). Cost-effectiveness was maintained in the 1-year analyses.

Conclusions:

Switching from treatment with BHI, IGlar, or NPH to BIAsp 30 (all?±?OGLDs) was found to be cost-effective in India, Indonesia, and Saudi Arabia, both in the long and short term.     

An indirect treatment comparison of the efficacy of insulin degludec/liraglutide (IDegLira) and insulin glargine/lixisenatide (iGlarLixi) in patients with type 2 diabetes uncontrolled on basal insulin

Aims: To obtain estimates of the relative treatment effects between insulin degludec/liraglutide (IDegLira) and insulin glargine U100/lixisenatide (iGlarLixi) in patients with type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin therapy.

Materials and methods: Data from phase 3 trials providing evidence for estimating the relative efficacy and safety of IDegLira vs iGlarLixi in patients uncontrolled on basal insulin-only regimens were used in this analysis. Outcomes of interest were changes in HbA_1c, body weight and insulin dose, and rate ratio of hypoglycemia. The indirect comparison of the reported trial findings followed the principles of Bucher et al.

Results: IDegLira was estimated to provide a 0.44 [95% CI?=?0.17–0.71] %-point reduction in HbA_1c compared with iGlarLixi. Body weight was reduced by 1.42 [95% CI?=?0.35–2.50] kg with IDegLira compared with iGlarLixi. Insulin dose was comparable between the two interventions. The rate of severe or blood glucose-confirmed (self-measured plasma glucose [SMPG]?≤?3.1?mmol/L) hypoglycemia with IDegLira was approximately half that of iGlarLixi (rate ratio?=?0.51 [95% CI?=?0.29–0.90]). However, using the American Diabetes Association definition of documented symptomatic hypoglycemia (SMPG ≤3.9?mmol/L) the rate was comparable between the two treatments (rate ratio?=?1.07 [95% CI?=?0.90–1.28]).

Limitations: The assumptions made in the indirect comparison and differences between the included trials in baseline HbA_1c levels, previous use of sulfonylureas, definitions of hypoglycemia, presence or absence of run-in period, the different duration of the trials, and the cross-over design of one of the trials.

Conclusions: The results of this indirect treatment comparison demonstrate that, among patients with T2DM uncontrolled on basal insulin, treatment with IDegLira results in a greater reduction of HbA_1c and a greater reduction in body weight compared with iGlarLixi at similar insulin doses.     

Evaluating drug cost per responder and number needed to treat associated with lixisenatide on top of glargine when compared to rapid-acting insulin intensification regimens on top of glargine,in patients with type 2 diabetes in the UK,Italy, and Spain

Objectives: This study investigated the cost per responder and number needed to treat (NNT) in type 2 diabetes mellitus (T2DM) patients for lixisenatide compared to insulin intensification regimens using composite endpoints in the UK, Italy, and Spain.

Methods: Efficacy and safety outcomes were obtained from GetGoal Duo-2, a 26-week phase 3 trial comparing lixisenatide vs insulin glulisine (IG) once daily (QD) and three times daily (TID). Response at week 26 was extrapolated to 52 weeks, assuming a maintained treatment effect, based on long-term evidence in other T2DM populations. Responders were defined using composite end-points, based on an HbA1c threshold and/or no weight gain and/or no hypoglycemia. The HbA1c threshold was varied in sensitivity analyses. Annual treatment costs were estimated in euros (1 GBP?=?1.26 EUR), including drug acquisition and resource use costs. Cost per responder was computed by dividing annual treatment costs per patient by the proportion of responders.

Results: Lixisenatide was associated with the lowest cost per responder for all composite end-points that included a weight-related component. For the main composite end-point of HbA1c ≤7.5% AND no weight gain AND no symptomatic hypoglycemia, cost per responder results were: UK: 6,867€, 8,746€, and 12,410€; Italy: 7,057€, 9,160€, and 12,844€; Spain: 8,370€, 11,365€, and 17,038€, for lixisenatide, IG QD, and TID, respectively. The NNT analysis showed that, for every 6.85 and 5.86 patients treated with lixisenatide, there was approximately one additional responder compared to IG QD and TID, respectively.

Limitations: A limitation of the clinical inputs is the lack of 52-week trial data from GetGoal Duo-2, which led to the assumption of a maintained treatment effect from week 26 to 52.

Conclusions: This analysis suggests lixisenatide is an efficient economic resource allocation in the UK, Italy, and Spain.     

Cost-effectiveness analysis of exenatide once-weekly versus dulaglutide,liraglutide, and lixisenatide for the treatment of type 2 diabetes mellitus: an analysis from the UK NHS perspective

Objective: To assess the cost-effectiveness of exenatide 2?mg once-weekly (EQW) compared to dulaglutide 1.5?mg QW, liraglutide 1.2?mg and 1.8?mg once-daily (QD), and lixisenatide 20?μg QD for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin.

Methods: The Cardiff Diabetes Model was applied to evaluate cost-effectiveness, with treatment effects sourced from a network meta-analysis. Quality-adjusted life years (QALYs) were calculated with health-state utilities applied to T2DM-related complications, weight changes, hypoglycemia, and nausea. Costs (GBP £) included drug treatment, T2DM-related complications, severe hypoglycemia, nausea, and treatment discontinuation due to adverse events. A 40-year time horizon was used.

Results: In all base-case comparisons, EQW was associated with a QALY gain per patient; 0.046 vs dulaglutide 1.5?mg; 0.102 vs liraglutide 1.2?mg; 0.043 vs liraglutide 1.8?mg; and 0.074 vs lixisenatide 20?μg. Cost per patient was lower for EQW than for liraglutide 1.8?mg (?£2,085); therefore, EQW dominated liraglutide 1.8?mg. The cost difference per patient between EQW and dulaglutide 1.5?mg, EQW and liraglutide 1.2?mg, and EQW and lixisenatide 20?μg was £27, £103, and £738, respectively. Cost per QALY gained with EQW vs dulaglutide 1.5?mg, EQW vs liraglutide 1.2?mg, and EQW vs lixisenatide 20?μg was £596, £1,004, and £10,002, respectively. In the probabilistic sensitivity analysis, the probability that EQW is cost-effective ranged from 76–99%.

Conclusion: Results suggest that exenatide 2?mg once-weekly is cost-effective over a lifetime horizon compared to dulaglutide 1.5?mg QW, liraglutide 1.2?mg QD, liraglutide 1.8?mg QD, and lixisenatide 20?μg QD for the treatment of T2DM in adults not adequately controlled on metformin alone.     

Comparison of costs and outcomes of dapagliflozin with other glucose-lowering therapy classes added to metformin using a short-term cost-effectiveness model in the US setting

Objective: To compare 1-year costs and benefits of dapagliflozin (DAPA), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with those of other treatments for type 2 diabetes (T2D), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), sulfonylureas (SUs), thiazolidinediones (TZDs), and dipeptidyl peptidase-4 inhibitors (DPP-4i), all combined with metformin.

Methods: A short-term decision-analytic model with a 1-year time horizon was developed from a payer’s perspective in the United States setting. Costs and benefits associated with four clinical end-points (glycated hemoglobin [A1C], body weight, systolic blood pressure [SBP], and risk of hypoglycemia) were evaluated in the analysis. The impact of DAPA and other glucose-lowering therapy classes on these clinical end-points was estimated from a network meta-analysis (NMA). Data for costs and quality-adjusted life-years (QALYs) associated with a per-unit change in these clinical end-points were taken from published literature. Drug prices were taken from an annual wholesale price list. All costs were inflation-adjusted to December 2016 costs using the medical care component of the consumer price index. Total costs (both medical and drug costs), total QALYs, and incremental cost-effectiveness ratios (ICERs) were estimated. Sensitivity analyses (SA) were performed to explore uncertainty in the inputs. To assess face validity, results from the short-term model were compared with long-term models published for these drugs.

Results: The total annual medical cost for DAPA was less than that for GLP-1RA ($186 less), DPP-4i ($1,142 less), SU ($2,474 less), and TZD ($1,640 less). Treatment with DAPA resulted in an average QALY gain of 0.0107, 0.0587, 0.1137, and 0.0715 per treated patient when compared with GLP-1RA, DPP-4i, SU, and TZD, respectively. ICERs for DAPA vs SU and TZD were $19,005 and $25,835, respectively. DAPA was a cost-saving option when compared with GLP-1RAs and DPP-4is. Among all four clinical end-points, change in weight had the greatest impact on total annual costs and ICERS. Sensitivity analysis showed that results were robust, and results from the short-term model were found to be similar to those of published long-term models.

Conclusion: This analysis showed that DAPA was cost-saving compared with GLP-1RA and DPP-4i, and cost-effective compared with SU and TZD in the US setting over 1 year. Furthermore, the results suggest that, among the four composite clinical end-points, change in weight and SBP had an impact on cost-effectiveness results.     

Retrospective study comparing healthcare costs and utilization between commercially insured patients with type 2 diabetes mellitus who are newly initiating exenatide once weekly or liraglutide in the United States

Abstract

Objective:

To compare healthcare costs and utilization between commercially insured patients with type 2 diabetes mellitus (T2DM) in the United States newly initiating exenatide once weekly (QW) or liraglutide.     

Real-world rates,predictors, and associated costs of hypoglycemia among patients with type 2 diabetes mellitus treated with insulin glargine: results of a pooled analysis of six retrospective observational studies

Abstract

Objective:

To evaluate the real-world rates of hypoglycemia and related costs among patients with type 2 diabetes mellitus (T2DM) who initiated insulin glargine with either a disposable pen or vial-and-syringe.

Methods:

Pooled data were evaluated from six previously published, retrospective, observational studies using US health plan insurance claims databases to investigate adults with T2DM who initiated insulin glargine. The current study evaluated baseline characteristics, hypoglycemic events, and costs during the 6 months prior to and 12 months following insulin glargine initiation. Comparisons were made between patients initiating treatment with a disposable pen (GLA-P) and vial-and-syringe (GLA-V). Multivariate analyses using baseline characteristics as covariates determined predictors of hypoglycemia after initiating insulin glargine.

Results:

This study included 23,098 patients (GLA-P: 14,911; GLA-V: 8187). Overall annual prevalence of hypoglycemia was low (6.3% overall, 2.2% related to hospital admission or emergency department visit). Prevalence was significantly lower with GLA-P (5.5% vs 7.7%; p?<?0.0001). Furthermore, average glycated hemoglobin HbA1c reduction was higher with GLA-P (?1.22% vs ?0.86%; p?=?0.0012). The average annual hypoglycemia-related cost associated with initiating insulin glargine was $293, with GLA-P being 46% lower than GLA-V ($225 vs $417; p?=?0.001). Patients who had already developed microvascular complications at the time of initiating insulin therapy were at higher risk for developing hypoglycemia.

Limitations:

This study is limited by the use of retrospective data and ICD-9-CM codes, which are subject to coding error. In addition, this pooled analysis used unmatched cohorts, with multivariate regression analyses employed to adjust for between-group differences. Finally, results describe a managed care sample and cannot be generalized to all patients with T2DM.

Conclusions:

Patients with T2DM initiating insulin glargine treatment showed low rates of hypoglycemia, especially when using a disposable pen device. Hypoglycemia-related costs were low, contributing a very small proportion to overall diabetes-related healthcare costs.     

Economic modelling of costs associated with outcomes reported for type 2 diabetes mellitus (T2DM) patients in the CANVAS and EMPA-REG cardiovascular outcomes trials

Aims: To model direct medical costs associated with reductions in cardiovascular disease (CVD) events in T2DM patients reported in the CANVAS and EMPA-REG trials, which assessed the cardiovascular safety of canagliflozin and empagliflozin, respectively.

Materials and methods: Costs were modeled from a US managed care organization (MCO) perspective for the CVD outcomes included in both trials: three-point major adverse cardiovascular event (MACE) and its components (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke), as well as heart failure requiring hospitalization. The rate of CVD events averted (difference between study drug and placebo) was projected to the portion of an MCO T2DM population matching the respective trial’s inclusion criteria. A targeted literature search for paid amounts directly associated with each CVD event provided the unit costs, which were applied to the projected number of events averted, to calculate costs avoided per member per year (PMPY). One-way sensitivity analyses were performed on events averted, unit costs, and percentages of trial-applicable patients.

Results: Based on three-point MACE events averted, costs avoided PMPY of $6.17 (range: $1.27–$10.94) for CANVAS and $2.75 ($0.19–$4.83) for EMPA-REG were estimated. Costs avoided for individual components of MACE ranged from $0.77 to $3.84 PMPY for CANVAS and from -$0.97 (additional costs) to $1.54 for EMPA-REG. PMPY costs avoided for heart failure were $2.72 for CANVAS and $1.32 for EMPA-REG.

Limitations and conclusions: Models assumed independent, non-recurrent outcomes and were restricted to medical costs directly associated with the trial-reported events. The reductions in CVD events in T2DM patients reported for both CANVAS and EMPA-REG project to a positive cost avoidance for these events in an MCO population. The analysis did not include an assessment of the impact on total cost, as the costs associated with adverse events, drug utilization or other clinical outcomes were not examined.