Document on a comprehensive approach to type 2 diabetes mellitus. / Documento de abordaje integral de la diabetes tipo 2.

OBJECTIVE: Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM. PARTICIPANTS: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology. METHODS: The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members. CONCLUSIONS: This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists.

The Economic Burden of Insulin-Related Hypoglycemia in Spain.

INTRODUCTION: An analysis was conducted to estimate the economic burden of insulin-related hypoglycemia in adults in Spain, derived from a novel concept developed for the UK known as the Local Impact of Hypoglycemia Tool. METHODS: Costs per severe and non-severe hypoglycemic episode were calculated for patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM). The costs per episode were applied to the population of adults with T1DM and T2DM using insulin in Spain according to the number of severe and non-severe episodes experienced per year. Costs were calculated using Spanish-specific resource costs and published values for resource utilization, including ambulance, accident and emergency (A&E) department, hospitalization, healthcare professional visits, and extra self-monitoring of blood glucose (SMBG) tests used in the week following the episode. A one-way sensitivity analysis on all model inputs was then performed. RESULTS: The cost of insulin-related hypoglycemia in Spain is estimated as €662.0 m per year, €292.6 m of which is due to severe episodes and €369.4 m to non-severe episodes. The cost per episode varies from €1.25 for patients with T1DM and €1.48 for patients with T2DM for a non-severe episode where extra SMBG testing after the episode is the only action taken, to €4378.22 for T1DM and €3005.74 for T2DM for a severe episode that was treated in hospital and requires an ambulance, A&E visit, hospitalization, and a diabetes specialist visit. A reduction in severe and non-severe hypoglycemia rates of just 20% could lead to considerable cost savings of €284,925 per 100,000 general population. CONCLUSION: This analysis highlights the substantial economic burden of hypoglycemia in Spain, and gives budget holders the ability to assess the costs of new treatments or patient education programs in relation to the potential cost savings due to lower hypoglycemia rates.

Cost-effectiveness analysis of insulin degludec compared with insulin glargine u100 for the management of type 1 and type 2 diabetes mellitus - from the Spanish National Health System perspective.

BACKGROUND: The objective of this study was to assess the cost-effectiveness of insulin degludec versus insulin glargine, from the Spanish NHS in three groups of patients. METHODS: A short-term cost utility model was developed to estimate effectiveness results in terms of the total number of hypoglycaemic events and their disutility impact throughout the year on the initial level of quality of life for patients in each treatment. RESULTS: Degludec was the dominant strategy for T2DM BOT and exhibited an incremental cost-effectiveness ratio of 52.70€/QALY and 11,240.88€/QALY for T1DM B/B and T2DM B/B, respectively. Lower costs are primarily driven by lower nocturnal and severe hypoglycaemic events, which were reduced versus IGlar. Improvements in clinical outcomes in all three patient groups are result of the reduced number of hypoglycaemic events showing 0.0211, 0.0328 and 0.0248 QALYs gained when compared to IGlar for T1DM B/B, T2DM BOT and T2DM B/B, respectively. Different scenario analyses showed that the ICERS were stable to plausible variations in the analysed parameters, except when the same number of SMBG for both treatments is used, with T2DM B/B showing an ICER over the accepted threshold. CONCLUSION: This analysis demonstrates that degludec is a cost-effective option in the Spanish NHS, when used in patients currently treated with long-acting insulin.

Liraglutide Versus Lixisenatide: Long-Term Cost-Effectiveness of GLP-1 Receptor Agonist Therapy for the Treatment of Type 2 Diabetes in Spain.

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists are used successfully in the treatment of patients with type 2 diabetes as they are associated with low hypoglycemia rates, weight loss and improved glycemic control. This study compared, in the Spanish setting, the cost-effectiveness of liraglutide 1.8 mg versus lixisenatide 20 µg, both GLP-1 receptor agonists, for patients with type 2 diabetes who had not achieved glycemic control targets on metformin monotherapy. METHODS: The IMS CORE Diabetes Model was used to project clinical outcomes and costs, expressed in 2015 Euros, over patient lifetimes. Baseline cohort data and treatment effects were taken from the 26-week, open-label LIRA-LIXI™ trial (NCT01973231). Treatment and management costs of diabetes-related complications were retrieved from published sources and databases. Future benefits and costs were discounted by 3% annually. Sensitivity analyses were conducted. RESULTS: Compared with lixisenatide 20 µg, liraglutide 1.8 mg was associated with higher life expectancy (14.42 vs. 14.29 years), higher quality-adjusted life expectancy [9.40 versus 9.26 quality-adjusted life years (QALYs)] and a reduced incidence of diabetes-related complications. Higher acquisition costs resulted in higher total costs for liraglutide 1.8 mg (EUR 42,689) than for lixisenatide 20 µg (EUR 42,143), but these were partly offset by reduced costs of treating diabetes-related complications (EUR 29,613 vs. EUR 30,636). Projected clinical outcomes and costs resulted in an incremental cost-effectiveness ratio of EUR 4113 per QALY gained for liraglutide 1.8 mg versus lixisenatide 20 µg. CONCLUSIONS: Long-term projections in the Spanish setting suggest that liraglutide 1.8 mg is likely to be cost-effective compared with lixisenatide 20 µg in type 2 diabetes patients who have not achieved glycemic control targets on metformin monotherapy. Liraglutide 1.8 mg presents a clinically and economically attractive treatment option in the Spanish setting.

Cost-Effectiveness Analysis of Incretin Therapy for Type 2 Diabetes in Spain: 1.8 mg Liraglutide Versus Sitagliptin.

OBJECTIVES: Metformin is the first-line therapy for most patients with type 2 diabetes, but the majority require treatment intensification at some stage due to the progressive nature of the disease. The 1860-LIRA-DPP-4 trial showed that liraglutide exhibited greater improvements compared with sitagliptin in glycated hemoglobin and body mass index in patients with type 2 diabetes inadequately controlled on metformin monotherapy. As a follow-up to a previously published cost-effectiveness analysis of 1.2 mg liraglutide versus sitagliptin in Spain, the aim of this analysis was to compare long-term projections of the clinical and cost implications associated with 1.8 mg liraglutide and sitagliptin. METHODS: For the modeling analysis, 52-week treatment effect data (as opposed to 26-week data in the previous analysis) were taken from the 1860-LIRA-DPP-4 trial, for adults with type 2 diabetes receiving 1.8 mg liraglutide or 100 mg sitagliptin daily in addition to metformin. Long-term (patient lifetime) projections of clinical outcomes and direct costs (2012 EUR) were made using a published and validated model of type 2 diabetes, with modeling assumptions as per the 1.2 mg liraglutide analysis. RESULTS: Liraglutide was associated with increased life expectancy (14.24 versus 13.87 years) and quality-adjusted life expectancy [9.24 versus 8.84 quality-adjusted life years (QALYs)] over sitagliptin. Improved clinical outcomes were attributable to the improvement in glycemic control, leading to a reduced incidence of diabetes-related complications, including renal disease, cardiovascular disease, ophthalmic and diabetic foot complications. Liraglutide was associated with increased direct costs (EUR 56,628 versus EUR 52,450), driven by increased pharmacy costs. Based on these estimates, liraglutide was associated with an incremental cost-effectiveness ratio of EUR 10,436 per QALY gained versus sitagliptin. CONCLUSIONS: A previous analysis has suggested that 1.2 mg liraglutide is cost-effective from a healthcare payer perspective in Spain, and the present analysis suggests that the 1.8 mg dose is also likely to be cost-effective.

Is treatment with liraglutide efficient?

In the current context of limited economic and health resources, efficiency of drug treatments is of paramount importance, and their clinical effects and related direct costs should therefore be analyzed. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus (T2DM) which, in addition to its normoglycemic effects, induces a significant improvement in body weight and several cardiovascular risk factors. The aim of this narrative review is to summarize the available evidence about the effects of liraglutide upon cardiovascular risk factors and how these improve its cost-effectiveness profile. Despite the relatively higher cost of liraglutide as compared to other alternative therapies, liraglutide has been shown to be cost-effective when clinical indicators and total costs associated to T2DM management are analyzed.

Incretin therapy for type 2 diabetes in Spain: a cost-effectiveness analysis of liraglutide versus sitagliptin.

INTRODUCTION: Treatment with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, which target the incretin axis, has the potential to improve glycemic control in type 2 diabetes patients without the weight gain associated with traditional therapies. To evaluate the relative cost-effectiveness of incretin therapies, the present study aimed to compare the long-term clinical and cost implications associated with liraglutide and sitagliptin in type 2 diabetes patients in Spain. METHODS: Data were taken from a randomized, controlled trial (NCT00700817) in which adults with type 2 diabetes failing metformin monotherapy were randomly allocated to receive either liraglutide 1.2 mg or sitagliptin 100 mg daily in addition to metformin. Long-term projections of clinical outcomes and direct costs (2012 EUR) based on observed treatment effects were made using a published and validated type 2 diabetes model. Costs were taken from published sources. Future costs and clinical benefits were discounted at 3% annually. Sensitivity analyses were performed. RESULTS: Liraglutide was associated with improved discounted life expectancy (14.05 versus 13.91 years) and quality-adjusted life expectancy [9.04 versus 8.87 quality-adjusted life years (QALYs)] compared to sitagliptin. Improved clinical outcomes were driven by improved glycemic control, leading to reduced incidence of diabetes-related complications, including renal disease, cardiovascular disease, ophthalmic and diabetic foot complications. Liraglutide was associated with increased direct costs of EUR 2,297, yielding an incremental cost-effectiveness ratio of EUR 13,266 per QALY gained versus sitagliptin. CONCLUSIONS: Liraglutide was projected to improve life expectancy, quality-adjusted life expectancy and reduce incidence of diabetes-related complication. Liraglutide is likely to be cost-effective versus sitagliptin from a healthcare payer perspective in Spain.