Cost-effectiveness of continuous subcutaneous insulin infusion in people with type 2 diabetes in the Netherlands

Aims: Up to 30% of insulin-treated type 2 diabetes patients are unable to achieve HbA1c targets despite optimization of insulin multiple daily injections (MDI). For these patients the use of continuous subcutaneous insulin infusion (CSII) represents a useful but under-utilized alternative. The aim of the present analysis was to examine the cost-effectiveness of initiating CSII in type 2 diabetes patients failing to achieve good glycemic control on MDI in the Netherlands. Methods: Long-term projections were made using the IMS CORE Diabetes Model. Clinical input data were sourced from the OpT2mise trial. The analysis was performed over a lifetime time horizon. The discount rates applied to future costs and clinical outcomes were 4% and 1.5% per annum, respectively. Results: CSII was associated with improved quality-adjusted life expectancy compared with MDI (9.38 quality-adjusted life years [QALYs] vs 8.95 QALYs, respectively). The breakdown of costs indicated that ～50% of costs were attributable to diabetes-related complications. Higher acquisition costs of CSII vs MDI were partially offset by the reduction in complications. The ICER was estimated at EUR 62,895 per QALY gained and EUR 60,474 per QALY gained when indirect costs were included. Conclusions: In the Netherlands, CSII represents a cost-effective option in patients with type 2 diabetes who continue to have poorly-controlled HbA1c despite optimization of MDI. Since the ICER falls below the willingness-to-pay threshold of EUR 80,000 per QALY gained, CSII is likely to represent good-value for money in the treatment of poorly-controlled T2D patients compared with MDI.     

Cost-effectiveness of G5 Mobile continuous glucose monitoring device compared to self-monitoring of blood glucose alone for people with type 1 diabetes from the Canadian societal perspective

Aims: To evaluate the cost-effectiveness of real-time continuous glucose monitoring (CGM) compared to self-monitoring of blood glucose (SMBG) alone in people with type 1 diabetes (T1DM) using multiple daily injections (MDI) from the Canadian societal perspective.

Methods: The IMS CORE Diabetes Model (v.9.0) was used to assess the long-term (50 years) cost-effectiveness of real-time CGM (G5 Mobile CGM System; Dexcom, Inc., San Diego, CA) compared with SMBG alone for a cohort of adults with poorly-controlled T1DM. Treatment effects and baseline characteristics of patients were derived from the DIAMOND randomized controlled clinical trial; all other assumptions and costs were sourced from published research. The accuracy and clinical effectiveness of G5 Mobile CGM is the same as the G4 Platinum CGM used in the DIAMOND randomized clinical trial. Base case assumptions included (a) baseline HbA1c of 8.6%, (b) change in HbA1c of –1.0% for CGM users vs –0.4% for SMBG users, and (c) disutilities of –0.0142 for non-severe hypoglycemic events (NSHEs) and severe hypoglycemic events (SHEs) not requiring medical intervention, and –0.047 for SHEs requiring medical resources. Treatment costs and outcomes were discounted at 1.5% per year.

Results: The incremental cost-effectiveness ratio for the base case G5 Mobile CGM vs SMBG was $33,789 CAD/quality-adjusted life-year (QALY). Sensitivity analyses showed that base case results were most sensitive to changes in percentage reduction in hypoglycemic events and disutilities associated with hypoglycemic events. The base case results were minimally impacted by changes in baseline HbA1c level, incorporation of indirect costs, changes in the discount rate, and baseline utility of patients.

Conclusions: The results of this analysis demonstrate that G5 Mobile CGM is cost-effective within the population of adults with T1DM using MDI, assuming a Canadian willingness-to-pay threshold of $50,000 CAD per QALY.     

Cost-effectiveness of insulin degludec compared with insulin glargine in a basal-bolus regimen in patients with type 1 diabetes mellitus in the UK

Abstract

Objective:

The aim of this study was to evaluate the cost-effectiveness of insulin degludec (IDeg) vs insulin glargine (IGlar) as part of a basal-bolus treatment regimen in adults with T1DM, using a short-term economic model.

Methods:

Data from two phase III clinical studies were used to populate a simple and transparent short-term model. The costs and effects of treatment with IDeg vs IGlar were calculated over a 12-month period. The analysis was conducted from the perspective of the UK National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results. The main outcome measure, the incremental cost-effectiveness ratio (ICER), was the cost per quality-adjusted life-year (QALY).

Results:

IDeg is a cost-effective treatment option vs IGlar in patients with T1DM on a basal-bolus regimen. The base case ICER was estimated at £16,895/QALY, which is below commonly accepted thresholds for cost-effectiveness in the UK. Sensitivity analyses demonstrated that the ICER was stable to variations in the majority of input parameters. The parameters that exerted the most influence on the ICER were hypoglycemia event rates, daily insulin dose, and disutility associated with non-severe nocturnal hypoglycemic events. However, even under extreme assumptions in the majority of analyses the ICERs remained below the commonly accepted threshold of £20,000–£30,000 per QALY gained.

Conclusions:

This short-term modeling approach accommodates the treat-to-target trial design required by regulatory bodies, and focuses on the impact of important aspects of insulin therapy such as hypoglycemia and dosing. For patients with T1DM who are treated with a basal-bolus insulin regimen, IDeg is a cost-effective treatment option compared with IGlar. IDeg may be particularly cost-effective for sub-groups of patients, such as those suffering from recurrent nocturnal hypoglycemia and those with impaired awareness of hypoglycemia.     

Long-term cost-effectiveness of insulin detemir versus NPH insulin in type 2 diabetes in Sweden

Abstract

Aim:

To evaluate the cost-effectiveness of insulin detemir vs. NPH insulin once daily, in patients with type 2 diabetes in the Swedish setting based on clinical data from a published randomized controlled trial.

Methods:

Projections of long-term outcomes were made using the IMS CORE Diabetes Model (CDM), based on clinical data from a 26-week randomized controlled trial that compared once daily insulin detemir and NPH insulin, when used to intensify insulin treatment in 271 patients with type 2 diabetes and body mass index (BMI) 25–40?kg/m². Trial results showed that insulin detemir was associated with a significantly lower incidence of hypoglycemic events and significantly less weight gain in comparison with NPH insulin. The analysis was conducted from a third party payer perspective and the base case analysis was performed over a time horizon of 40 years and future costs and clinical outcomes were discounted at a rate of 3% per year.

Results:

Insulin detemir was associated with higher mean (SD) quality-adjusted life expectancy (5.42 [0.10] vs. 5.31 [0.10] quality-adjusted life years [QALYs]) and lower overall costs (SEK 378,539 [10,372] vs. SEK 384,216 [11,230]; EUR 33,794 and EUR 34,300, respectively, where 1 EUR?=?11.2015 SEK) compared with NPH insulin. Sensitivity analysis showed that the principal driver of the benefits associated with insulin detemir was the lower rate of hypoglycemic events (major and minor events) vs. NPH insulin, suggesting that detemir might also be cost-saving over a shorter time horizon. Limitations of the analysis include the use of data from a trial outside Sweden in the Swedish setting.

Conclusions:

Based on clinical input data derived from a previously published randomized controlled trial, it is likely that in the Swedish setting insulin detemir would be cost-saving in comparison with NPH insulin for the treatment of patients with type 2 diabetes.     

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.     

The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes

Objective: To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin.

Methods: The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled, despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study. The Swedish healthcare perspective was adopted for this analysis; costs are reported in €EUR to aid interpretation. The main outcome measure was the cost per quality-adjusted life-year (QALY) gained with exenatide BID compared to lispro TID.

Results: Exenatide BID was associated with an incremental cost of €1,270 and a QALY increase of +0.64 compared with lispro TID over 40 years. The cost per QALY gained with exenatide BID compared with lispro TID was €1,971, which is within conventional limits of cost-effectiveness. Cost-effectiveness results were generally robust to alternative assumptions and values for key model parameters.

Limitations: Extrapolation of trial data over the longer term can be influenced by modeling and parameter uncertainty. Cost-effectiveness results were generally insensitive to alternative values of key model input parameters and across scenarios.

Conclusions: The addition of exenatide BID rather than insulin lispro to basal insulin is associated with similar or better clinical outcomes. Illustrated from the Swedish healthcare perspective, analysis with the Cardiff Diabetes Model demonstrated that exenatide BID represents a cost-effective treatment alternative to lispro TID as add-on therapy in type 2 diabetes patients insufficiently controlled on basal insulin.     

Evaluation of the long-term cost-effectiveness of liraglutide therapy for patients with type 2 diabetes in France

Objectives:

The present study aimed to compare the projected long-term clinical and cost implications associated with liraglutide, sitagliptin and glimepiride in patients with type 2 diabetes mellitus failing to achieve glycemic control on metformin monotherapy in France.

Methods:

Clinical input data for the modeling analysis were taken from two randomized, controlled trials (LIRA-DPP4 and LEAD-2). Long-term (patient lifetime) projections of clinical outcomes and direct costs (2013 Euros; €) were made using a validated computer simulation model of type 2 diabetes. Costs were taken from published France-specific sources. Future costs and clinical benefits were discounted at 3% annually. Sensitivity analyses were performed.

Results:

Liraglutide was associated with an increase in quality-adjusted life expectancy of 0.25 quality-adjusted life years (QALYs) and an increase in mean direct healthcare costs of €2558 per patient compared with sitagliptin. In the comparison with glimepiride, liraglutide was associated with an increase in quality-adjusted life expectancy of 0.23 QALYs and an increase in direct costs of €4695. Based on these estimates, liraglutide was associated with an incremental cost-effectiveness ratio (ICER) of €10,275 per QALY gained vs sitagliptin and €20,709 per QALY gained vs glimepiride in France.

Conclusion:

Calculated ICERs for both comparisons fell below the commonly quoted willingness-to-pay threshold of €30,000 per QALY gained. Therefore, liraglutide is likely to be cost-effective vs sitagliptin and glimepiride from a healthcare payer perspective in France.     

Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway

Abstract

Background:

Lixisenatide is a potent, selective and short-acting once daily prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin and body weight by clinically significant amounts in patients with type 2 diabetes treated with basal insulin, with limited risk of hypoglycemia.     

The cost-effectiveness and budget impact of stepwise addition of bolus insulin in the treatment of type 2 diabetes: evaluation of the FullSTEP trial

Background and aims:

Intensification of basal insulin-only therapy in type 2 diabetes is often achieved through addition of bolus insulin 3-times daily. The FullSTEP trial demonstrated that stepwise addition (SWA) of bolus insulin aspart was non-inferior to full basal-bolus (FBB) therapy and reduced the rate of hypoglycemia. Here the cost-effectiveness and budget impact of SWA is evaluated.

Methods:

Cost-effectiveness and budget impact models were developed to assess the cost and quality-of-life (QoL) implications of intensification using SWA compared with FBB in the US setting. At assessment, SWA patients added one bolus dose to their current regimen if the HbA1c target was not met. SWA patients reaching three bolus doses used FBB event rates. Outcomes were evaluated at trial end and projected annually up to 5 years. Models captured hypoglycemic events, the proportion meeting HbA1c target, and self-measured blood glucose. Event rates and QoL utilities were taken from trial data and published literature. Costs were evaluated from a healthcare-payer perspective, reported in 2013 USD, and discounted (like clinical outcomes) at 3.5% annually. This analysis applies to patients with HbA1c 7.0–9.0% and body mass index <40?kg/m².

Results:

SWA was associated with improved QoL and reduced costs compared with FBB. Improvement in QoL and cost reduction were driven by lower rates of hypoglycemia. Sensitivity analyses showed that outcomes were most influenced by the cost of bolus insulin and QoL impact of symptomatic hypoglycemia. Budget impact analysis estimated that, by moving from FBB to SWA, a health plan with 77,000 patients with type 2 diabetes, of whom 7.8% annually intensified to basal-bolus therapy, would save USD 1304 per intensifying patient over the trial period.

Conclusions:

SWA of bolus insulin should be considered a beneficial and cost-saving alternative to FBB therapy for the intensification of treatment in type 2 diabetes.     

Cost-effectiveness of saxagliptin vs glimepiride as a second-line therapy added to metformin in Type 2 diabetes in China

Abstract

Objective:

This study aims to estimate the long-term cost-effectiveness of saxagliptin?+?metformin (SAXA?+?MET) vs glimepiride?+?metformin (GLI?+?MET) in patients with Type 2 diabetes mellitus (T2DM) inadequately controlled with MET in China.     

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.     

Cost-effectiveness of insulin detemir compared with neutral protamine Hagedorn insulin in patients with type 1 diabetes using a basal-bolus regimen in five European countries

Abstract

Objectives: The aim of this analysis was to evaluate the long-term clinical and economic outcomes associated with insulin detemir and neutral protamine Hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 1 diabetes in Belgian, French, German, Italian and Spanish settings.

Methods: The published and validated IMS CORE Diabetes Model was used to make long-term projections of life expectancy, quality-adjusted life expectancy and direct medical costs. The analysis was based on patient characteristics and treatment effects from a 2-year randomised controlled trial. Events were projected for a time horizon of 50 years. Potential uncertainty using a modelling approach was addressed.

Results: Basal-bolus therapy with insulin detemir was projected to improve quality-adjusted life expectancy by 0.45 years versus NPH in the German setting, with similar improvements in the other countries. Insulin detemir was associated with cost savings in Belgium, Germany and Spain. In France and Italy, lifetime costs were slightly higher in the detemir arm, leading to incremental cost-effectiveness ratios of €519 per QALY gained and €3,256 per QALY gained, respectively.

Conclusions: Compared to NPH, insulin detemir is likely to be a dominant treatment strategy in Belgium, Germany and Spain and highly cost-effective in France and Italy in patients with type 1 diabetes.     

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.     

Effect of type 1 diabetes on school performance in a dynamic world: new analysis exploring Swedish register data

This paper investigates if the effect of type 1 diabetes mellitus (T1DM) on school performance, documented in prior research, has changed in more recent birth cohorts of children using national Swedish population register data. The issue is of interest because management and treatment of the disease have improved over the last decades and, furthermore, because of changes in the educational grading system. Despite these changes, data indicate a persistent negative effect of T1DM on compulsory and upper secondary school grades with a standardized effect size of ?0.109 and ?0.070, respectively, and the results appear only marginally smaller compared to earlier findings in cohorts completing school under the previous grading system. Moreover, the results are consistent for alternative model specifications and econometric estimation strategies. Whereas access to new treatment technologies and improved diabetes management strategies has reduced the burden of diabetes in daily life, the results from this study indicate that continued efforts are needed to improve the situation in school for children with T1DM to prevent potential long-term socio-economic consequences.     

Cost-effectiveness analysis of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese patients with Type 2 diabetes mellitus inadequately controlled by oral therapies

Abstract

Objective:

To estimate cost-effectiveness of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese type 2 diabetes patients not well controlled by oral anti-diabetic (OAD) agents.     

Economic outcomes of exenatide vs liraglutide in type 2 diabetes patients in the United States: results from a retrospective claims database analysis

Abstract

Objective:

The safety and efficacy of the GLP-1 receptor agonists exenatide BID (exenatide) and liraglutide for treating type 2 diabetes mellitus (T2DM) have been established in clinical trials. Effective treatments may lower overall treatment costs. This study examined cost offsets and medication adherence for exenatide vs liraglutide in a large, managed care population in the US.

Methods:

This was a retrospective cohort analysis comprising adult patients with T2DM who initiated exenatide or liraglutide between 1/1/2010 and 6/30/2010 and had 6 months pre-index and post-index continuous eligibility. Patients were propensity score-matched to controls for baseline differences. Medication adherence was measured by proportion of days covered (PDC). Paired t-test and McNemar’s test were used to compare outcomes.

Results:

Matched exenatide and liraglutide cohorts (n?=?1347 pairs) had similar average total 6-month follow-up costs ($6688 vs $7346). However, exenatide patients had significantly lower mean pharmacy costs ($2925 vs $3272, p?<?0.001). Among liraglutide patients, patients receiving the 1.8?mg dose had significantly higher average total costs compared to those receiving the 1.2?mg dose ($8031 vs $6536, p?=?0.026), with higher mean pharmacy costs in the 1.8?mg cohort ($3935 vs $3146, p?<?0.001). There were no significant differences in inpatient or outpatient costs or medication adherence between groups (mean PDC: exenatide 56% vs liraglutide 57%, p?=?0.088).

Limitations:

The study assumed that all information needed for case classification and matching of cohorts was present and not differential across cohorts. The study did not control for covariates that were unavailable, such as HbA1c and duration of diabetes.

Conclusions:

Patients initiating exenatide vs liraglutide for T2DM had similar medication adherence and total healthcare costs; however, exenatide patients had significantly lower total pharmacy costs. Patients prescribed 1.8?mg liraglutide had significantly higher costs compared to those on 1.2?mg.