Dataset Information

The Cost-Effectiveness of Alogliptin Versus Sulfonylurea as Add-on Therapy to Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus.

ABSTRACT:

Introduction

ENDURE (ClinicalTrials.gov identifier, NCT00856284), a multicenter, double-blind, active-controlled study of 2639 patients with uncontrolled type 2 diabetes mellitus (T2DM), found that metformin in combination with alogliptin (12.5 and 25 mg doses), when compared to standard add-on therapy (sulfonylurea, SU), exerted sustained antihyperglycemic effects over 2 years. This economic analysis of ENDURE aimed to quantify the relationship between increased glycemic durability and cost-effectiveness of alogliptin in the UK clinical setting, and communicate its sustained glycemic benefit in economic terms.

Methods

Using baseline characteristics and treatment effects from the ENDURE trial population, between-group cost-effectiveness analyses compared the combined use of metformin and alogliptin (MET + ALO_12.5/25) in patients with inadequately controlled T2DM, as an alternative to metformin and SU (MET + SU). In scenario analyses, an intragroup cost-effectiveness analysis compared MET + ALO_12.5/25 with MET + SU; a between-group cost-effectiveness analysis also compared MET + ALO_12.5/25 versus MET + SU within a subpopulation of patients who achieved HbA1c control (<7.5%) at 2 years on study drug.

Results

Compared with baseline profiles of patients, combination therapies with alogliptin or SU were associated with improvements in length and quality of life and were cost-effective at established norms. Despite increased drug acquisition costs, alogliptin at 12.5 mg and 25 mg doses resulted in greater predicted lifetime quality-adjusted life year (QALY) gains with associated incremental cost-effectiveness ratios (ICERs) of £10,959/QALY and £7217/QALY compared to SU, respectively.

Conclusion

The ENDURE trial and the present cost-effectiveness analysis found that the glycemic durability of alogliptin therapy was associated with improved long-term patient outcomes, QALY gains, and ICERs that were cost-effective when evaluated against standard threshold values. Alogliptin therefore represents a cost-effective treatment alternative to SU as add-on therapy to metformin in patients with poorly managed T2DM.

Funding

Takeda Development Centre Europe Ltd.

SUBMITTER: Gordon J

PROVIDER: S-EPMC5118244 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionInternational and Danish guidelines recommend the use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors already in second line in the management of type 2 diabetes (T2D). The objective of this study was to evaluate the long-term cost-effectiveness (CE) of subcutaneous (SC) semaglutide (GLP-1 RA) versus empagliflozin (SGLT-2 inhibitor) in individuals with T2D uncontrolled on metformin alone from a Danish payer's perspective.MethodsCost-effectiveness analyses (CEA) were conducted from a Danish payer's perspective, using the IQVIA Core Diabetes model (CDM 9.5), with a time horizon of 50 years and an annual discount of 4% on costs and effects. Patients received either SC semaglutide or empagliflozin, in addition to metformin, until HbA1c threshold of 7.5% (58 mmol/mol) was reached, following which treatment intensification with insulin glargine in addition to empagliflozin or SC semaglutide plus metformin was considered. Baseline cohort characteristics and treatment effects were sourced from a published CEA. Utilities and cost of diabetes-related complications were also obtained from published sources. Treatment costs were derived from Danish official sources. Scenario analyses were also performed to test the accuracy of the base case results.ResultsIndividuals with T2D on SC semaglutide plus metformin gained 0.065 life-years (LYs) and 0.130 quality-adjusted LYs (QALYs), respectively, at an incremental cost of DKK 96,923 (€ 13,031) compared to empagliflozin plus metformin, resulting in an incremental cost-effectiveness ratio (ICER) of DKK 745,561(€ 100,239) per QALY gained. The probabilistic sensitivity analysis (PSA) results showed that the SC semaglutide plus metformin was cost-effective in 19% of simulations assuming a willingness-to-pay (WTP) threshold of DKK 357,100 (€ 48,011)/QALY gained. Duration of therapy with SC semaglutide seems the key driver of results.ConclusionThe current analyses suggest that SC semaglutide plus metformin is not cost-effective compared to empagliflozin plus metformin from a Danish payer's perspective.

Project description:IntroductionFew patients with type 2 diabetes mellitus (T2DM) achieve recommended glycemic control targets in the Czech Republic. Novel therapies, such as fixed-ratio combinations of basal insulin plus glucagon-like peptide-1 receptor agonists, may contribute to better glycemic control. In the analysis presented here, the present analysis assessed the long-term cost-effectiveness of two fixed-ratio combinations, IDegLira (insulin degludec/liraglutide) and iGlarLixi (insulin glargine/lixisenatide), for the treatment of patients with T2DM inadequately controlled with basal insulin from a healthcare payer perspective in the Czech Republic.MethodsA cost-effectiveness analysis was performed over patient lifetimes using the IQVIA CORE Diabetes Model. Treatment effects were obtained from an indirect treatment comparison as no head-to-head data for IDegLira versus iGlarLixi are currently available. IDegLira was compared with two iGlarLixi pens (100 U/mL insulin glargine + 33 μg/mL and 50 μg/mL of lixisenatide, respectively). Direct medical costs associated with pharmaceutical interventions, screening and diabetes-related complications were captured. Deterministic and probabilistic sensitivity analyses were performed.ResultsIDegLira was associated with gains in life expectancy of 0.11 years and in quality-adjusted life expectancy of 0.14 quality-adjusted life-years (QALYs) versus iGlarLixi, due to a lower cumulative incidence and delayed onset of diabetes-related complications. IDegLira was also associated with higher projected costs due to higher acquisition costs; however, these were partially offset by cost savings from avoided complications. IDegLira was associated with incremental cost-effectiveness ratios of Czech Koruna (CZK) 695,998 and CZK 348,323 per QALY gained versus iGlarLixi pens containing 33 and 50 μg/mL of lixisenatide, respectively. These ratios were below the commonly used willingness-to-pay threshold of CZK 1,200,000 per QALY gained.ConclusionThe present analysis indicated that IDegLira was associated with clinical benefits relative to iGlarLixi over patient lifetimes and was likely to be cost-effective in the treatment of patients with T2DM uncontrolled on basal insulin in the Czech Republic.FundingNovo Nordisk. Plain language summary is available for this article.

Project description:IntroductionAlogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), approved for the treatment of type 2 diabetes mellitus (T2DM). There currently exists no comparative data to support the use of alogliptin in combination with metformin (met) and sulfonylurea (SU). A decision-focused network meta-analysis (NMA) was performed to compare the relative efficacy and safety of alogliptin 25 mg once daily to other DPP-4 inhibitors as part of a triple therapy regimen for patients inadequately controlled on metformin and SU dual therapy.MethodsA systematic literature review was conducted to identify published papers of randomized controlled trials (RCTs) that compared alogliptin with other DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) at their Summary of Product Characteristics (SmPC) recommended daily doses, added on to metformin and SU. Comprehensive comparative analysis involving frequentist meta-analysis and Bayesian NMA compared alogliptin to each DPP-4 inhibitor separately and collectively as a group. Quasi-random effect models were introduced when random effect models could not be estimated.ResultsThe review identified 2186 articles, and 94 full-text articles were assessed for eligibility. Eight RCTs contained appropriate data for inclusion in the NMA. All analyses over all trial population sets produced very similar results, and show that alogliptin 25 mg is as least as effective (as measured by change in HbA1c from baseline, but supported by other outcome measures: change in body weight and FPG from baseline) and safe (as measured by incidence of hypoglycemia and adverse events leading to study discontinuation) as all the other DPP-4 inhibitors in triple therapy.ConclusionThis decision-focused systematic review and NMA demonstrated alogliptin 25 mg daily to have similar efficacy and safety compared to other DPP-4 inhibitors, for the treatment of T2DM in adults inadequately controlled on metformin and SU. (Funded by Takeda Development Centre Americas; EXAMINE ClinicalTrials.gov number, NCT00968708).

Project description:BackgroundOral semaglutide was approved in 2019 for blood glucose control in patients with type 2 diabetes mellitus (T2DM) and was the first oral glucagon-like peptide 1 receptor agonist (GLP-1 RA). T2DM is associated with substantial healthcare expenditures in the US, so the cost of a new intervention should be weighed against clinical benefits.ObjectiveThis study evaluated the budget impact of a treatment pathway with oral semaglutide 14 mg daily versus oral sitagliptin 100 mg daily among patients not achieving target glycated hemoglobin (HbA1c) level despite treatment with metformin.MethodsThis study used the validated IQVIA™ CORE Diabetes Model to simulate the treatment impact of oral semaglutide 14 mg and sitagliptin 100 mg over a 5-year time horizon from a US healthcare sector (payer) perspective. Trial data (PIONEER 3) informed cohort characteristics and treatment effects, and literature sources informed event costs. Population and market share data were from the literature and data on file. The analysis evaluated the estimated budget impact of oral semaglutide 14 mg use for patients currently using sitagliptin 100 mg considering both direct medical and treatment costs to understand the impact on total cost of care, given underlying treatment performance and impact on avoidable events.ResultsIn a hypothetical plan of 1 million lives, an estimated 1993 patients were treated with sitagliptin 100 mg in the target population. Following these patients over 5 years, the incremental direct medical and treatment costs of a patient using oral semaglutide 14 mg versus sitagliptin 100 mg was $US16,562, a 70.7% increase (year 2019 values). A hypothetical payer would spend an additional $US3,300,143 (7.1%) over 5 years for every 10% of market share that oral semaglutide 14 mg takes away from sitagliptin 100 mg. Univariate and scenario analyses with alternate inputs and assumptions demonstrated consistent results.ConclusionsUse of oral semaglutide 14 mg in patients currently receiving sitagliptin 100 mg substantially increases the budget impact for patients with T2DM whose blood glucose level is not controlled with metformin over a 5-year time horizon for US healthcare payers.

Project description:BACKGROUND: Insulin analogues may be associated with fewer episodes of hypoglycemia than conventional insulins. However, they are costly alternatives. We compared the cost-effectiveness of insulin analogues and conventional insulins used to treat type 1 and type 2 diabetes mellitus in adults. METHODS: We conducted a cost-effectiveness evaluation of insulin analogues versus conventional insulins using the Center for Outcomes Research Diabetes Model. We compared rapid-acting analogues (insulin aspart and insulin lispro) with regular human insulin, and long-acting analogues (insulin glargine and insulin detemir) with neutral protamine Hagedorn insulin. We derived clinical information for the comparisons from meta-analyses of randomized controlled trials. We obtained cost and utility estimates from published sources. We performed sensitivity analyses to test the robustness of our results. RESULTS: For type 1 diabetes, insulin aspart was more effective and less costly than regular human insulin. Insulin lispro was associated with an incremental cost of Can$28,996 per quality-adjusted life-year. The incremental cost per quality-adjusted life-year was Can$87,932 for insulin glargine and Can$387,729 for insulin detemir, compared with neutral protamine Hagedorn insulin. For type 2 diabetes, insulin aspart was associated with an incremental cost of Can$22,488 per quality-adjusted life-year compared with regular human insulin. For insulin lispro, the incremental cost was Can$130,865. Compared with neutral protamine Hagedorn insulin, insulin detemir was less effective and more costly. Insulin glargine was associated with an incremental cost of Can$642,994 per quality-adjusted life-year. The model was sensitive to changes in the effect size of hemoglobin A(1c) and to decrements applied to utility scores when fear of hypoglycemia was included as a factor. INTERPRETATION: The cost-effectiveness of insulin analogues depends on the type of insulin analogue and whether the patient receiving the treatment has type 1 or type 2 diabetes. With the exception of rapid-acting insulin analogues in type 1 diabetes, routine use of insulin analogues, especially long-acting analogues in type 2 diabetes, is unlikely to represent an efficient use of finite health care resources.

Project description:BackgroundWe assessed the cost-effectiveness of the glucagon-like peptide 1 receptor agonists liraglutide 1.8 mg and lixisenatide 20 μg (both added to basal insulin) in patients with type 2 diabetes (T2D) in Sweden.MethodsThe Swedish Institute for Health Economics cohort model for T2D was used to compare liraglutide and lixisenatide (both added to basal insulin), with a societal perspective and with comparative treatment effects derived by indirect treatment comparison (ITC). Drug prices were 2016 values, and all other costs 2015 values. The cost-effectiveness of IDegLira (fixed-ratio combination of insulin degludec and liraglutide) versus lixisenatide plus basal insulin was also assessed, under different sets of assumptions.ResultsFrom the ITC, decreases in HbA1c were -1.32% and -0.43% with liraglutide and lixisenatide, respectively; decreases in BMI were -1.29 and -0.65 kg/m2, respectively. An estimated 2348 cases of retinopathy, 265 of neuropathy and 991 of nephropathy would be avoided with liraglutide compared with lixisenatide in a cohort of 10,000 patients aged over 40 years. In the base-case analysis, total direct costs were higher with liraglutide than lixisenatide, but costs associated with complications were lower. The cost/quality-adjusted life-year (QALY) for liraglutide added to basal insulin was SEK30,802. Base-case findings were robust in sensitivity analyses, except when glycated haemoglobin (HbA1c) differences for liraglutide added to basal insulin were abolished, suggesting these benefits were driving the cost/QALY. With liraglutide 1.2 mg instead of liraglutide 1.8 mg (adjusted for efficacy and cost), liraglutide added to basal insulin was dominant over lixisenatide 20μg.IDegLira was dominant versus lixisenatide plus basal insulin when a defined daily dose was used in the model.ConclusionsThe costs/QALY for liraglutide, 1.8 or 1.2 mg, added to basal insulin, and for IDegLira (all compared with lixisenatide 20 μg added to basal insulin) were below the threshold considered low by Swedish authorities. In some scenarios, liraglutide and IDegLira were cost-saving.