Long-term health economic benefits of sensor-augmented pump therapy vs continuous subcutaneous insulin infusion alone in type 1 diabetes: a UK perspective

Aims/hypothesis:

Continuous subcutaneous insulin infusion (CSII) is an important treatment option for type 1 diabetes patients unable to achieve adequate glycemic control with multiple daily injections (MDI). Combining CSII with continuous glucose monitoring (CGM) in sensor-augmented pump therapy (SAP) with a low glucose-suspend (LGS) feature may further improve glycemic control and reduce the frequency of hypoglycemia. A cost-effectiveness analysis of SAP?+?LGS vs CSII plus self-monitoring of blood glucose (SMBG) was performed to determine the health economic benefits of SAP?+?LGS in type 1 diabetes patients using CSII in the UK.

Methods:

Cost-effectiveness analysis was performed using the CORE diabetes model. Treatment effects were sourced from the literature, where SAP?+?LGS was associated with a projected HbA_1c reduction of ?1.49% vs ?0.62% for CSII, and a reduced frequency of severe hypoglycemia. The time horizon was that of patient lifetimes; future costs and clinical outcomes were discounted at 3.5% and 1.5% per annum, respectively.

Results:

Projected outcomes showed that SAP?+?LGS was associated with higher mean quality-adjusted life expectancy (17.9 vs 14.9 quality-adjusted life years [QALYs], SAP?+?LGS vs CSII), and higher life expectancy (23.8 vs 21.9 years), but higher mean lifetime direct costs (GBP 125,559 vs GBP 88,991), leading to an incremental cost-effectiveness ratio (ICER) of GBP 12,233 per QALY gained for SAP?+?LGS vs CSII. Findings of the base-case analysis remained robust in sensitivity analyses.

Conclusions/interpretation:

For UK-based type 1 diabetes patients with poor glycemic control, the use of SAP?+?LGS is likely to be cost-effective compared with CSII plus SMBG.     

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.     

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.     

The association between the severity of chronic kidney disease and medical costs among patients with type 2 diabetes

Aims: Examine healthcare costs across chronic kidney disease (CKD) stages for US patients with type 2 diabetes (T2D).

Materials and methods: IQVIA Real World Data Adjudicated Claims linked electronic medical records and insurance claims from January 1, 2012 through March 31, 2017 were used for this retrospective study. Adults diagnosed with T2D and comorbid CKD were included. General linear models incorporating splines were constructed, and information from these regressions were used to inform the relationship between medical costs and CKD. Multivariable analyses controlled for patient characteristics, vital signs, general health, prior medication use, prior visit to specialists, index A1c, and year of index date.

Results: There were 6,645 individuals who met the study criteria. Results generally indicate sharp increases in annual total medical costs and non-drug medical costs in the 1?year post-period for patients with Stage 4 or 5 CKD (estimated glomerular filtration rate [eGFR]?≤?30?mL/min/1.73 m²) with each 1 point reduction in eGFR from 30 associated with an increase of $1,870 in all-cause total medical costs (p?<?0.0001) and $1,805 of all-cause non-drug medical costs (p?<?0.0001). Similarly, each point decline below 30?mL/min was associated annual cost increases of $1,701 for CKD-related total medical costs, $1,695 for CKD-related non-drug medical costs, $173 for diabetes-related medical costs, and $187 for diabetes-related non-drug medical costs (all p?<?0.0001).

Limitations: The investigation included only patients with medical insurance and laboratory test results, and results may not be generalizable to all T2D patients with CKD. The methodology allowed us to determine associations, not causation, and potential confounders, such as duration of diabetes, diet, exercise, or social support, could not be assessed.

Conclusions: Results indicate there are sharp and significant increases in medical costs among T2D patients with Stage 4 and 5 CKD compared to those with earlier stages of CKD.     

Clinical and economic benefits of professional CGM among people with type 2 diabetes in the United States: analysis of claims and lab data

Background: It is estimated that one in 10 people in the US have a diagnosis of diabetes. Type 2 diabetes accounts for 95% of all cases in the US, with annual costs estimated to be $246 billion per year. This study investigated the impact of a glucose-measuring intervention to the burden of type 2 diabetes.

Objective: This analysis seeks to understand how professional continuous glucose monitoring (professional CGM) impacts clinical and economic outcomes when compared to patients who are not prescribed professional CGM.

Methods: This study utilized a large healthcare claims and lab dataset from the US, and identified a cohort of patients who were prescribed professional CGM as identified by CPT codes 95250 and 95251. It calculated economic and clinical outcomes 1 year before and 1 year after the use of professional CGM, using a generalized linear model.

Results: Patients who utilized professional CGM saw an improvement in hemoglobin A1C. The “difference-in-difference” calculation for A1C was shown to be –0.44%. There was no statistically significant difference in growth of total annual costs for people who used professional CGM compared to those who did not ($1,270, p?=?.08). Patients using professional CGM more than once per year had a –$3,376 difference in the growth of total costs (p?=?.05). Patients who used professional CGM while changing their diabetes treatment regimen also had a difference of –$3,327 in growth of total costs (p?=?.0023).

Conclusion: Significant clinical benefits were observed for patients who used professional CGM. Economic benefits were observed for patients who utilized professional CGM more than once within a 1-year period or who used it during a change of diabetes therapy. This suggests that professional CGM may help decrease rising trends in healthcare costs for people with type 2 diabetes, while also improving clinical outcomes.     

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.     

基于机器学习的妊娠期糖尿病智能预测系统设计与实现

为帮助有效识别患有妊娠期糖尿病的孕妇,提前干预治疗,降低其潜在风险,设计并开发了妊娠期糖尿病智能预测系统。首先,在对比10种机器学习模型的基础上对临床数据集进行数据归一化和特征筛选,减少模型计算复杂度和一些使模型不稳定的特征;其次,使用Stacking算法对10种不同的机器学习模型进行集成,分别搭建2个集成模型Stacking1和Stacking2,比较集成模型的性能;最后,基于PyQt5设计妊娠期糖尿病智能预测系统,预测孕妇患妊娠期糖尿病的风险,并给出建议。结果表明：使用10个机器学习模型以及2个集成模型对GDM进行预测,发现GBDT的预测结果高于其他机器学习模型,集成模型Stacking2将多个异质学习器相结合表现出较高的准确性和可靠性,且评价指标Accuracy、Precision、Recall、AUC分别为0.900 9、0.901 2、0.900 7、0.900 7,均高于同类模型。智能预测系统能有效预测妊娠期糖尿病的风险,能够及早发现易患病人群,并提供妊娠期糖尿病的科普知识,从而加强对易患病人群的健康管理,降低妊娠期糖尿病发生的风险。     

Predictors of glycemic control and diabetes-related costs among type 2 diabetes patients initiating therapy with liraglutide in the United States

Objective:

Liraglutide has been shown to significantly improve glycemic control and reduce body weight while minimizing the risk of hypoglycemia in adult patients with type 2 diabetes (T2D). This study aimed to identify characteristics that predict clinical and economic outcomes associated with liraglutide therapy in clinical practice in the US.

Methods:

Using the Truven Health MarketScan Laboratory Database, glycemic control (A1C <7%) and diabetes-related costs were evaluated in T2D patients initiating liraglutide between January 1, 2010 and June 30, 2012. Patients were required to have ≥1 post-index claim for liraglutide and A1C values at baseline and 6 months follow-up. All valid values of baseline A1C were included. Patients previously treated with GLP-1 receptor agonist(s) or insulin, or with evidence of type 1 diabetes, pregnancy, or gestational diabetes during the study period were excluded. Multivariable regression models were used to identify predictors of glycemic control and diabetes-related costs.

Results:

Of 417 patients newly treated with liraglutide, 54.0% achieved glycemic control (A1C <7%) during follow-up. Factors associated with increased odds of glycemic control during follow-up were: being female, POS/EPO health plan type, baseline A1C, early liraglutide initiation (0–1 prior oral anti diabetics [OADs] vs ≥2), adherence to liraglutide (defined as the proportion of days covered [PDC]), and diabetic retinopathy. Being female, earlier liraglutide initiation (0–1 prior OADs), and higher patient share of liraglutide costs were associated with significantly lower diabetes-related costs during follow-up. Factors associated with significantly higher post-index diabetes-related costs were: higher baseline A1C, baseline use of sulfonylureas, and diabetic retinopathy.

Conclusions:

Within this commercially-insured population of T2D patients treated with liraglutide, gender, baseline A1C, early liraglutide initiation (0–1 prior OADs), diabetic retinopathy, better adherence, and patient share of liraglutide costs were associated with increased odds of achieving glycemic control and the odds of having higher or lower diabetes-related costs.     

Evaluation of a patient self-directed mealtime insulin titration algorithm: a US payer perspective

Objective To model the potential economic impact of implementing the AUTONOMY once daily (Q1D) patient self-titration mealtime insulin dosing algorithm vs standard of care (SOC) among a population of patients with Type 2 diabetes living in the US.

Methods Three validated models were used in this analysis: The Treatment Transitions Model (TTM) was used to generate the primary results, while both the Archimedes (AM) and IMS Core Diabetes Models (IMS) were used to test the veracity of the primary results produced by TTM. Models used data from a ‘real world’ representative sample of patients (2012 US National Health and Nutrition Examination Survey) that matched the characteristics of US patients enrolled in the randomized controlled trial ‘AUTONOMY’ cohort. The base-case time horizon was 10 years.

Results The modeling results from TTM demonstrated that total costs in the base-case were reduced by $1732, with savings predicted to occur as early as year 1. Results from the three models were consistent, showing a reduction in total costs for all sensitivity analyses.

Limitations Data from short-term clinical trials were used to develop long-term projections. The nature of such extrapolation leads to increased uncertainty.

Conclusion The results from all three models indicate that the AUTONOMY Q1D algorithm has the potential to abate total costs as early as the first year.     

Resource utilisation and costs in patients with type 2 diabetes mellitus treated with insulin glargine or conventional basal insulin under real-world conditions in Germany: LIVE-SPP study

Objective: To assess and compare the total costs relevant to diabetes care in patients with type 2 diabetes mellitus (T2D) treated at specialised diabetes practices with either insulin glargine- or conventional basal insulin (neutral protamine Hagedorn [NPH])-based therapies from the German statutory health insurance (SHI) perspective.

Methods: The Long Acting Insulin Glargine Versus NPH Cost Evaluation in Specialised Practices (LIVE-SPP) study is an observational, retrolective, multicentre longitudinal cost comparison in adults with T2D. Costs were evaluated from the German SHI perspective based on official 2005 prices. Average total costs per patient for insulin glargine-versus NPH-based therapies were compared using multivariate general linear modelling. Sensitivity analyses were performed by varying the main cost factors by ± 25%.

Results: Patients (n=1,024, 512 patients per cohort) were on average 62 years of age, with an average 8-year diabetes history at study start. The average unadjusted total annual costs per patient were €1,868.41 (95% CI 1,744.27–1,992.56) for insulin glargine-based vs. €2,063.72 (95% CI 1,922.91–2,204.54) for NPH-based therapies. Average adjusted total annual costs per patient between insulin glargine- (€1,241.13) and NPH-based therapies (€1,607.86) were statistically significantly different (p=0.0004). The economic advantage for insulin glargine-based therapies resulted mainly from fewer blood glucose measurements and other diabetes-related materials (e.g. needles). The savings remained stable in one-way sensitivity analyses.

Conclusions: The LIVE-SPP study suggests that insulin glargine-based therapies may offer an economic advantage over NPH-based therapies.