Cost-Effectiveness of Dipeptidylpeptidase-4 Inhibitors Added to Metformin in Patients With Type 2 Diabetes in China.

Purpose: Dipeptidylpeptidase-4 (DPP-4) inhibitors, including linagliptin, alogliptin, saxagliptin, sitagliptin, and vildagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM) patients in China. This study assessed the economic outcomes of different DPP-4 inhibitors in patients with T2DM inadequately controlled with metformin in the Chinese context. Materials and Methods: In this study, the validated Chinese Outcomes Model for T2DM (COMT) was conducted to project economic outcomes from the perspective of Chinese healthcare service providers. Efficacy and safety, medical expenditure, and utility data were derived from the literature, which were assigned to model variables. The primary outputs of the model included the lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analysis was conducted to assess the potential uncertainties of parameters. Results: Of the five competing strategies, alogliptin 25 mg strategy yielded the most significant health outcome, which associated with improvements in discounted QALY of 0.007, 0.014, 0.011, and 0.022 versus linagliptin 5 mg, saxagliptin 5 mg, sitagliptin 100 mg and vildagliptin50 mg, respectively. The sitagliptin 100 mg strategy was the cheapest option. The ICER of alogliptin 25 mg against sitagliptin 100 mg strategy was $6,952 per additional QALY gained, and the rest of the strategies were dominated or extended dominated. The most influential parameters were the cost of DPP-4 inhibitors and their treatment efficacy. Conclusions: These results suggested that alogliptin was a preferred treatment option compared with other DPP-4 inhibitors for Chinese patients whose T2DM are inadequately controlled on metformin monotherapy.

[Efficacy of Saxagliptin for Blood Glucose Control in Hemodialysis Patients with Diabetes].

Studies on the drug saxagliptin (marketed in Japan since 2013) suggest favorable efficacy in hemodialysis patients, but included small sample sizes. Noting that some hemodialysis patients at our medical institution had been switched to saxagliptin 2.5 mg from treatment with other dipeptidyl peptidase-4 inhibitors, we decided to evaluate the effects of switching to saxagliptin on blood glucose control in these patients. The study included 11 patients. Before switching drugs, six of the patients used teneligliptin 20 mg and five used linagliptin 5 mg. Mean glycated albumin (GA) from before to 4 months after switching tended to increase in the previous users of teneligliptin 20 mg (18.4±3.0% to 19.5±2.7%) and tended to decrease in the previous users of linagliptin 5 mg (18.8±3.3% to 17.7±1.4%). Lack of a substantial change in GA when the previous users of teneligliptin 20 mg and linagliptin 5 mg were switched to saxagliptin 2.5 mg indicates that these three agents might have comparable antihyperglycemic profiles when used in patients on hemodialysis. Future research following from this pilot study must evaluate the risk of cardiac failure and incidences of adverse events in a larger population, to investigate the long-term efficacy and safety of switching to saxagliptin.

Healthcare costs among adults with type 2 diabetes initiating saxagliptin or linagliptin: a US-based claims analysis.

OBJECTIVE: To compare healthcare costs of adults with type 2 diabetes (T2D) after initiation of saxagliptin or linagliptin, two antidiabetic medications in the dipeptidyl peptidase-4 inhibitor medication class. METHODS: Patients with T2D who were at least 18 years old and initiated saxagliptin or linagliptin (index date) between 1 June 2011 and 30 June 2014 were identified in the MarketScan Commercial and Medicare Supplemental Databases. All-cause healthcare costs and diabetes-related costs (T2D diagnosis on a medical claim and/or an antidiabetic medication claim) were measured in the 1 year follow-up period. Saxagliptin and linagliptin initiators were matched using propensity score methods. Cost ratios (CRs) and predicted costs were estimated from generalized linear models and recycled predictions. RESULTS: There were 34,560 saxagliptin initiators and 18,175 linagliptin initiators identified (mean ages 57 and 59; 55% and 56% male, respectively). Before matching, saxagliptin initiators had significantly lower all-cause total healthcare costs than linagliptin initiators (mean = $15,335 [SD $28,923] vs. mean = $20,069 [SD $48,541], p < .001) and significantly lower diabetes-related total healthcare costs (mean = $6109 [SD $13,851] vs. mean = $7393 [SD $26,041], p < .001). In matched analyses (n = 16,069 per cohort), saxagliptin initiators had lower all-cause follow-up costs than linagliptin initiators (CR = 0.953, 95% CI = 0.932-0.974, p < .001; predicted costs = $17,211 vs. $18,068). There was no significant difference in diabetes-related total costs after matching; however, diabetes-related medical costs were significantly lower for saxagliptin initiators (CR = 0.959, 95% CI = 0.927-0.993, p = 0.017; predicted costs = $3989 vs. $4159). CONCLUSIONS: Adult patients with T2D initiating treatment with saxagliptin had lower total all-cause healthcare costs and diabetes-related medical costs over 1 year compared with patients initiating treatment with linagliptin.

Cost-effectiveness of vildagliptin for people with type 2 diabetes mellitus in Brazil; findings and implications.

INTRODUCTION: Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4, indicated for the treatment of type 2 diabetes mellitus, combined or not with metformin. This study aims to evaluate the cost-effectiveness of vildagliptin in the Brazilian context. Areas covered: Using MEDLINE, Cochrane Library, Lilacs and CRD, six studies were selected for the economic models. This study utilised cost data in the Brazilian health system to provide the context. Expert commentary: Type 2 diabetes mellitus is an epidemic disease and represents a challenge for all health care systems. Although guidelines clearly define first-line treatment, there are several other promising treatments. Vildagliptin is one of them, resulting in a mean lifetime increase of 0.31 years compared to metformin alone and 1.19 more life years compared to other metformin combinations. Considering observational data, life years with dual vildagliptin-containing treatments were 0.37 more compared to other dual treatments. However, its high cost versus generic metformin and its unclear safety profile weakens its subsequent cost-effectiveness. Consequently, the incorporation of vildagliptin or its combination with metformin is currently not recommended for the Brazilian Health Care System. This may change as more data becomes available.

Adherence, Persistence, and Health Care Costs for Patients Receiving Dipeptidyl Peptidase-4 Inhibitors.

BACKGROUND: The dipeptidyl peptidase-4 (DPP-4) inhibitors are among the newer, yet more established, classes of diabetes medications. OBJECTIVE: To compare adherence, persistence, and health care costs among patients taking DPP-4 inhibitors. METHODS: Claims were extracted from Humana Medicare Advantage Prescription Drug (MAPD) or commercial plans for patients aged > 18 years with ≥ 1 prescription filled for a DPP-4 inhibitor between July 1, 2011, and March 31, 2013. The first prescription claim for a DPP-4 inhibitor established the index date and index medication; 12-month pre-index and post-index data were analyzed. The Diabetes Complications Severity Index (DCSI) was used to assess a level of baseline diabetes-related comorbidities. Adherence (proportion of days covered [PDC] ≥ 80%) and persistence (< 31-day gap) measures were compared before and after, adjusting for DCSI, pre-index insulin, age, and gender. Post-index costs (in 2013 U.S. dollars) were compared using general linear modeling (GLM) to adjust for pre-index costs, DCSI, pre-index insulin, age, and gender. RESULTS: Based on study criteria, 22,860 patients with MAPD coverage (17,292 sitagliptin, 4,282 saxagliptin, and 1,286 linagliptin) and 3,229 patients with commercial coverage (2,368 sitagliptin, 643 saxagliptin, and 218 linagliptin) were included. For MAPD patients, the mean age was 70-72 years, and females represented 50%-52% of patients. For commercial patients, mean age was 55-56 years, and females represented 44% of patients. Clinical indicators for patients on linagliptin showed a higher comorbidity level than sitagliptin or saxagliptin cohorts (MAPD DCSI 3.0 vs 2.4 and 2.2, P < 0.001; commercial DCSI 1.2 vs. 0.9 and 0.9, P < 0.001); a higher use of pre-index insulin (MAPD 22% vs. 15% and 14%, P < 0.001; commercial 18% vs. 11% and 10%, P = 0.003); and higher mean pre-index costs (MAPD $14,448 vs. $11,818 and $10,399, P < 0.001; commercial $13,868 vs. $9,357 and $8,223, P = 0.016). For the MAPD cohort, the unadjusted PDC was lower for linagliptin patients (67%) compared with saxagliptin (72%) or sitagliptin (72%) patients (P < 0.001). Significant differences were still seen when adjusted for covariates. Linagliptin patients were more likely to be nonpersistent (73%) than those on saxagliptin (65%) or sitagliptin (67%; P < 0.01 for adjusted and unadjusted comparisons). For the commercial population, there were no significant differences in mean PDC between the 3 groups (linagliptin 70%, saxagliptin 72%, and sitagliptin 74%; P = 0.096). Dichotomized comparisons of nonpersistence were significantly different (linagliptin 65%, saxagliptin 62%, and sitagliptin 57%; P = 0.010), although upon adjustment using a Cox proportional hazard model, no significant differences were found. When controlling for other factors, post-index adjusted health care costs were similar between the medication cohorts (MAPD: sitagliptin = $13,913, saxagliptin = $13,651, and linagliptin = $13,859; commercial: sitagliptin = $11,677, saxagliptin = $12,059, and linagliptin = $11,163; all P > 0.25). CONCLUSIONS: For MAPD and commercial populations, baseline patient demographics were similar between the 3 DPP-4 inhibitor groups, but the linagliptin group may have had more complex patients (higher pre-index costs, higher DCSI, and more use of insulin). For the MAPD population, patients on linagliptin were less adherent and persistent than patients taking sitagliptin or saxagliptin for all unadjusted and adjusted comparisons. For the commercial population, which was notably smaller, these differences were in the same direction, but not all were statistically significant. When controlling for baseline factors, 12-month post-index direct medical health care costs were similar between index DPP-4 inhibitors. DISCLOSURES: No external funding was provided for this research. The project was done as part of internal work by Humana employees. Rascati received no compensation. None of the authors have any financial disclosures or conflicts of interests to report. Worley and Everhart are employees of Comprehensive Health Insights, a subsidiary of Humana, and Meah is an employee of Humana. Discussion of the adherence and persistence data was presented as a poster at the Academy of Managed Care Pharmacy Nexus Conference, October 2015. Cost data were presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research 18th Annual European Congress, November 2015. Study concept and design were contributed by Rascati, Worley, and Meah, along with Everhart. Rascati took the lead in data collection, assisted by Meah, and data interpretation was performed by all the authors. The manuscript was written primarily by Rascati, along with Worley, Everhart, and Meah, and revised by Rascati, Everhart, and Worley, with assistance from Meah.

Cost-Effectiveness of Saxagliptin versus Acarbose as Second-Line Therapy in Type 2 Diabetes in China.

OBJECTIVE: This study assessed the long-term cost-effectiveness of saxagliptin+metformin (SAXA+MET) versus acarbose+metformin (ACAR+MET) in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on MET alone. METHODS: Systematic literature reviews were performed to identify studies directly comparing SAXA+MET versus ACAR+MET, and to obtain diabetes-related events costs which were modified by hospital surveys. A Cardiff Diabetes Model was used to estimate the long-term economic and health treatment consequences in patients with T2DM. Costs (2014 Chinese yuan) were calculated from the payer's perspective and estimated over a patient's lifetime. RESULTS: SAXA+MET predicted lower incidences of most cardiovascular events, hypoglycemia events and fatal events, and decreased total costs compared with ACAR+MET. For an individual patient, the quality-adjusted life-years (QALYs) gained with SAXA+MET was 0.48 more than ACAR+MET at a cost saving of ¥18,736, which resulted in a cost saving of ¥38,640 per QALY gained for SAXA+MET versus ACAR+MET. Results were robust across various univariate and probabilistic sensitivity analyses. CONCLUSION: SAXA+MET is a cost-effective treatment alternative compared with ACAR+MET for patients with T2DM in China, with a little QALYs gain and lower costs. SAXA is an effective, well-tolerated drug with a low incidence of adverse events and ease of administration; it is anticipated to be an effective second-line therapy for T2DM treatment.

Healthcare Costs Among Adults with Type 2 Diabetes Initiating DPP-4 Inhibitors.

INTRODUCTION: Oral antidiabetes medications, including dipeptidyl peptidase-4 inhibitors (DPP-4is) saxagliptin and sitagliptin, are used for the treatment of type 2 diabetes (T2D). The study objective was to compare all-cause and diabetes-related costs following initiation of saxagliptin or sitagliptin. METHODS: Patients aged ≥ 18 years initiating saxagliptin or sitagliptin between January 1, 2009 and January 31, 2012 in the Truven Health MarketScan Commercial and Medicare Supplemental databases were identified. Patients were required to have continuous enrollment for ≥ 365 days before and ≥ 365 days after the index date (date of the first saxagliptin or sitagliptin claim). Additionally, patients were required to have a claim with a T2D diagnosis (ICD-9-CM 250.×0, 250.×2) and no claims for a DPP-4i medication before the index date. All-cause and diabetes-related medical costs and total costs (including pharmacy costs) were captured over the 1-year follow-up period. Generalized linear models with log link and gamma distribution were fit to compare costs between the two cohorts using cost ratios, controlling for patient baseline characteristics. Recycled prediction methods were used to generate adjusted predicted costs and confidence intervals. RESULTS: The final sample comprised 3354 saxagliptin initiators and 26,895 sitagliptin initiators. The average age of saxagliptin and sitagliptin initiators was 57 years and just over 50% were males. After adjusting for baseline characteristics, saxagliptin patients had significantly lower average all-cause medical costs (cost ratio = 0.901, P < 0.001; predicted mean costs: $8687 vs. $9646) compared with sitagliptin patients over the 1-year follow-up. Findings were consistent for diabetes-related medical costs (cost ratio = 0.890, P < 0.001; predicted mean costs: $2180 vs. $2450). Total costs were also lower for saxagliptin initiators (cost ratio = 0.950, P = 0.002; predicted mean costs: $13,911 vs. $14,651) over the 1-year follow-up period. CONCLUSION: Initiation of treatment with saxagliptin was associated with lower medical costs over 1 year compared with initiation of sitagliptin among adults with T2D. FUNDING: AstraZeneca.

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

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. METHODS: The Cardiff Model was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews and hospital surveys were conducted to obtain patients profiles, clinical data, and costs. Health insurance costs (2014¥) were estimated over a 40-year period. One-way and probabilistic sensitivity analyses were performed. RESULTS: SAXA + MET had lower predicted incidences of cardiovascular and hypoglycemia events and a decreased total cost compared with GLI + MET (¥241,072,807 vs ¥285,455,177). There were increased numbers of quality-adjusted life-years (QALYs; 1.01/patient) and life-years (Lys; 0.03/patient) gained with SAXA + MET compared with GLI + MET, and the incremental cost of SAXA + MET vs GLI + MET (-¥44,382) resulted in -¥43,883/QALY and -¥1,710,926/LY gained with SAXA + MET. Sensitivity analyses confirmed that the results were robust. CONCLUSION: In patients with T2DM in China, SAXA + MET was more cost-effective and was well tolerated with fewer adverse effects (AEs) compared with GLI + MET. As a second-line therapy for T2DM, SAXA may address some of the unmet medical needs attributable to AEs in the treatment of T2DM.

Cost-effectiveness of metformin plus vildagliptin compared with metformin plus sulphonylurea for the treatment of patients with type 2 diabetes mellitus: a Portuguese healthcare system perspective.

OBJECTIVE: To evaluate the cost-effectiveness of vildagliptin plus metformin vs generic sulphonylurea plus metformin in patients with type 2 diabetes mellitus, not controlled with metformin, from a Portuguese healthcare system perspective. METHODS: A cost-effectiveness model was constructed using risk equations from the UK Prospective Diabetes Study Outcomes Model with a 10,000-patient cohort and a lifetime horizon. The model predicted microvascular and macrovascular complications and mortality in yearly cycles. Patients entered the model as metformin monotherapy failures and switched to alternative treatments (metformin plus basal-bolus insulin and subsequently metformin plus intensive insulin) when glycated hemoglobin A1c >7.5% was reached. Baseline patient characteristics and clinical variables were derived from a Portuguese epidemiological study. Cost estimates were based on direct medical costs only. One-way and probabilistic sensitivity analyses were conducted to test the robustness of the model. RESULTS: There were fewer non-fatal diabetes-related adverse events (AEs) in patients treated with metformin plus vildagliptin compared with patients treated with metformin plus sulphonylurea (6752 vs 6815). Addition of vildagliptin compared with sulphonylurea led to increased drug acquisition costs but reduced costs of AEs, managing morbidities, and monitoring patients. Treatment with metformin plus vildagliptin yielded a mean per-patient gain of 0.1279 quality-adjusted life years (QALYs) and a mean per-patient increase in total cost of €1161, giving an incremental cost-effectiveness ratio (ICER) of €9072 per QALY. Univariate analyses showed that ICER values were robust and ranged from €4195 to €16,052 per QALY when different parameters were varied. LIMITATIONS: The model excluded several diabetes-related morbidities, such as peripheral neuropathy and ulceration, and did not model second events. Patients were presumed to enter the model with no diabetes-related complications. CONCLUSION: Treatment with metformin plus vildagliptin compared with metformin plus sulphonylurea is expected to result in a lower incidence of diabetes-related AEs and to be a cost-effective treatment strategy.

Pharmacoeconomic analysis of DPP-4 inhibitors.

Dipeptidyl peptidase-4 (DPP-4) inhibitors and other incretin-related drugs have attracted attention as antidiabetic agents, but they are expensive. The Japanese government has adopted a policy of reducing healthcare costs, and medical institutions must provide medical care while considering economic efficiency. This study was a comparative survey of the usage, treatment effectiveness, and cost of DPP-4 inhibitors. The subjects were patients prescribed DPP-4 inhibitors (sitagliptin, vildagliptin, and alogliptin) at Gifu Municipal Hospital between February 2010 and August 2011. HbA1c: Japan Diabetes Society values (%) and concomitant antidiabetic agents were surveyed for 12 weeks after the start of DPP-4 inhibitors. A cost-effectiveness analysis showed that the cost required for a 0.1% decrease in HbA1c for 12 weeks was the lowest with vildagliptin (2,478 yen; decrease in HbA1c: 0.75% +/- 0.85%). In a cost analysis with a virtual cohort of 1000 patients, the number of patients who achieved the treatment target (HbA1c 6.5%) was estimated with respect to a virtual cohort created based on the HbA1c level (7.59 +/- 1.13%) at baseline of 307 patients, in cases assuming the use of each DPP-4 inhibitor. In addition, the incremental cost-effectiveness ratio (ICER) was obtained with sitagliptin 50 mg as the reference. The number of patients achieving the treatment target was the highest with vildagliptin 100 mg (413 of 1000 patients), and the estimated ICER of 28,359 yen was the lowest. Robustness was also confirmed with a sensitivity analysis. These results suggest that vildagliptin provides a superior cost-benefit.

Cost-effectiveness and budget impact of saxagliptine as additional therapy to metformin for the treatment of diabetes mellitus type 2 in the Brazilian private health system.

OBJECTIVES: To compare costs and clinical benefits of three additional therapies to metformin (MF) for patients with diabetes mellitus type 2 (DM2). METHODS: A discrete event simulation model was built to estimate the cost-utility ratio (cost per quality-adjusted life years [QALY]) of saxagliptine as an additional therapy to MF when compared to rosiglitazone or pioglitazone. A budget impact model (BIM) was built to simulate the economic impact of saxagliptine use in the context of the Brazilian private health system. RESULTS: The acquiring medication costs for the hypothetical patient group analyzed in a time frame of three years, were R$ 10,850,185, R$ 14,836,265 and R$ 14,679,099 for saxagliptine, pioglitazone and rosiglitazone, respectively. Saxagliptine showed lower costs and greater effectiveness in both comparisons, with projected savings for the first three years of R$ 3,874 and R$ 3,996, respectively. The BIM estimated cumulative savings of R$ 417,958 with the repayment of saxagliptine in three years from the perspective of a health plan with 1,000,000 covered individuals. CONCLUSION: From the perspective of private paying source, the projection is that adding saxagliptine with MF save costs when compared with the addition of rosiglitazone or pioglitazone in patients with DM2 that have not reached the HbA1c goal with metformin monotherapy. The BIM of including saxagliptine in the reimbursement lists of health plans indicated significant savings on the three-year horizon.

Custo-efetividade e impacto orçamentário da saxagliptina como terapia adicional à metformina para o tratamento do diabetes mellitus tipo 2 no sistema de saúde suplementar do Brasil / Cost-effectiveness and budget impact of saxagliptine as additional therapy to metformin for the treatment of diabetes mellitus type 2 in the brazilian private health system

OBJETIVOS: Comparar custos e benefícios clínicos de três terapias adicionais à metformina (MF) para pacientes com diabetes mellitus tipo 2 (DMT2). MÉTODOS: Um modelo de simulação de eventos discretos foi construído para estimar a relação custo-utilidade (custo por QALY) da saxagliptina como uma terapia adicional à MF comparada à rosiglitazona ou pioglitazona. Um modelo de impacto orçamentário (BIM - Budget Impact Model) foi construído para simular o impacto econômico da adoção de saxagliptina no contexto do Sistema Suplementar de Saúde brasileiro. RESULTADOS: O custo de aquisição da medicação para o grupo de pacientes hipotéticos analisados, para o horizonte temporal de três anos, foi de R$ 10.850.185,00, R$ 14.836.265,00 e R$ 14.679.099,00 para saxagliptina, pioglitazona e rosiglitazona, respectivamente. Saxagliptina exibiu menores custos e maior efetividade em ambas as comparações, com economias projetadas para os três primeiros anos de -R$ 3.874,00 e -R$ 3.996,00, respectivamente. O BIM estimou uma economia cumulativa de R$ 417.958,00 com o reembolso da saxagliptina em três anos a partir da perspectiva de uma operadora de plano de saúde com 1 milhão de vidas cobertas. CONCLUSÃO: Da perspectiva da fonte pagadora privada, a projeção é de que o acréscimo de saxagliptina à MF poupe custos quando comparado ao acréscimo de rosiglitazona ou pioglitazona em pacientes com DMT2 que não atingiram a meta de hemoglobina glicada (HbA1c) com metformina em monoterapia. O BIM, para a inclusão de saxagliptina nas listas de reembolso das operadoras de planos de saúde, indicou uma economia significativa para o horizonte de 3 anos.

OBJECTIVES: To compare costs and clinical benefits of three additional therapies to metformin (MF) for patients with diabetes mellitus type 2 (DM2). METHODS: A discrete event simulation model was built to estimate the cost-utility ratio (cost per quality-adjusted life years [QALY]) of saxagliptine as an additional therapy to MF when compared to rosiglitazone or pioglitazone. A budget impact model (BIM) was built to simulate the economic impact of saxagliptine use in the context of the Brazilian private health system. RESULTS: The acquiring medication costs for the hypothetical patient group analyzed in a time frame of three years, were R$ 10,850,185, R$ 14,836,265 and R$ 14,679,099 for saxagliptine, pioglitazone and rosiglitazone, respectively. Saxagliptine showed lower costs and greater effectiveness in both comparisons, with projected savings for the first three years of R$ 3,874 and R$ 3,996, respectively. The BIM estimated cumulative savings of R$ 417,958 with the repayment of saxagliptine in three years from the perspective of a health plan with 1,000,000 covered individuals. CONCLUSION: From the perspective of private paying source, the projection is that adding saxagliptine with MF save costs when compared with the addition of rosiglitazone or pioglitazone in patients with DM2 that have not reached the HbA1c goal with metformin monotherapy. The BIM of including saxagliptine in the reimbursement lists of health plans indicated significant savings on the three-year horizon.

Cost-effectiveness of saxagliptin (Onglyza®) in type 2 diabetes in Sweden.

AIM: The objective of this study was to investigate the cost-effectiveness of saxagliptin (Onglyza(®)), a DPP-4 inhibitor, plus metformin compared with a sulphonylurea (SU) (Glipizide) plus metformin in Swedish patients not well controlled on metformin alone. METHODS: Data from a 52-week clinical trial comparing saxagliptin and glipizide in combination with metformin was used in a simulation model to estimate long term complications in a cohort of type 2 diabetes patients. The model estimates the incidence of microvascular and macrovascular complications, diabetes-specific mortality, all-cause mortality, and ultimately, costs and quality-adjusted life years (QALYs) associated with the investigated treatment strategies. Costs and QALYs were estimated for a lifetime time horizon. RESULTS: Compared with SU+metformin, the cost per QALY gained with saxagliptin+metformin is approximately SEK 91,000. Patients on saxagliptin+metformin gain 0.10 QALYs on average, at an incremental cost of around SEK 9500. The cost-effectiveness results were robust to various sensitivity analyses. CONCLUSIONS: This study demonstrates that, over a patient's lifetime, the addition of saxagliptin to metformin is associated with improvements in quality-adjusted life years compared with SU in patients with type 2 diabetes. Saxagliptin treatment is a cost-effective treatment alternative for type 2 diabetes in patients not well-controlled on metformin alone.

The cost-effectiveness of saxagliptin versus NPH insulin when used in combination with other oral antidiabetes agents in the treatment of type 2 diabetes mellitus in Poland.

BACKGROUND: This study compared the health and economic benefits of saxagliptin versus insulin as second-line therapy with either metformin (MET) or sulfonylurea (SU) after failure of the respective monotherapies for patients with type 2 diabetes in Poland. METHODS: The cost-effectiveness was assessed using a previously published diabetes model. Disease progression, utilities, and effects of changes in glycosylated hemoglobin (HbA1c), weight, and hypoglycemic events were taken from published studies, and Polish sources were used where possible. RESULTS: MET + saxagliptin reduced severe hypoglycemic complications and weight versus MET + insulin, with an incremental benefit of 0.13 quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) of 27,454 Polish zloty (PLN) ($9,966 U.S.) per QALY gained. SU + saxagliptin showed an incremental benefit of 0.14 QALYs and ICER of 24,663 PLN ($8,953 U.S.) per QALY gained versus SU + insulin, with reduced incidence of symptomatic and severe hypoglycemias. Results were most sensitive to disutilities associated with weight gain, hypoglycemia, injection fear, HbA1c changes, threshold for switching treatment, and patients' age. Results were robust to various model assumptions and inputs. Using a willingness-to-pay threshold of 100,000 PLN ($36,300 U.S.) per QALY gained, the probability that saxagliptin is cost-effective in these analyses was 74% (MET) and 76% (SU). CONCLUSIONS: Saxagliptin in combination with MET or SU is likely to represent a cost-effective treatment option in Polish patients with type 2 diabetes failing first-line treatment.

Incretin-based therapies in the management of type 2 diabetes: rationale and reality in a managed care setting.

In addition to the hypoglycemia and weight gain associated with many treatments for type 2 diabetes, alpha-glucosidase inhibitors, thiazolidinediones, metformin, sulfonylureas, and the glinides do not address all of the multiple defects existing in the pathophysiology of the disease. Cumulatively, these oral agents address the influx of glucose from the gastrointestinal tract, impaired insulin activity, and acute beta-cell dysfunction in type 2 diabetes; however, until recently, there were no means to deal with the inappropriate hyperglucagonemia or chronic beta-cell-decline characteristic of the disease. The recently introduced incretin-based therapies serve to address some of the challenges associated with traditionally available oral antidiabetic agents. In addition to improving beta-cell function, stimulating insulin secretion, and inhibiting glucagon secretion, these agents reduce appetite, thereby stabilizing weight and/or promoting weight loss in patients with type 2 diabetes. Of the incretin-based therapies, both the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and inhibit glucagon secretion. The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 receptor agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and saxagliptin. Earlier and more frequent use of these incretin-based therapies is recommended in the treatment of type 2 diabetes, based on their overall safety and ability to achieve the glycosylated hemoglobin level goal. As such, both the American Diabetes Association and the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) treatment algorithms recommend the use of incretin-based therapy in both treatment-naive and previously treated patients. The AACE/ACE guidelines clearly state that these agents should not be limited to third- or fourth-line therapy.

Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation.

BACKGROUND: In May 2008, the National Institute for Health and Clinical Excellence (NICE) issued an updated guideline [clinical guideline (CG) 66] for the management of all aspects of type 2 diabetes. This report aims to provide information on new drug developments to support a 'new drugs update' to the 2008 guideline. OBJECTIVE: To review the newer agents available for blood glucose control in type 2 diabetes from four classes: the glucagon-like peptide-1 (GLP-1) analogue exenatide; dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin and vildagliptin; the long-acting insulin analogues, glargine and detemir; and to review concerns about the safety of the thiazolidinediones. DATA SOURCES: The following databases were searched: MEDLINE (1990-April 2008), EMBASE (1990-April 2008), the Cochrane Library (all sections) Issue 2, 2008, and the Science Citation Index and ISI Proceedings (2000-April 2008). The websites of the American Diabetes Association, the European Association for the Study of Diabetes, the US Food and Drug Administration, the European Medicines Evaluation Agency and the Medicines and Healthcare Products Regulatory Agency were searched, as were manufacturers' websites. REVIEW METHODS: Data extraction was carried out by one person, and checked by a second. Studies were assessed for quality using standard methods for reviews of trials. Meta-analyses were carried out using the Cochrane Review Manager (RevMan) software. Inclusion and exclusion criteria were based on current standard clinical practice in the UK, as outlined in NICE CG 66. The outcomes for the GLP-1 analogues, DPP-4 inhibitors and the long-acting insulin analogues were: glycaemic control, reflected by glycated haemoglobin (HbA1c) level, hypoglycaemic episodes, changes in weight, adverse events, quality of life and costs. Modelling of the cost-effectiveness of the various regimes used the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model. RESULTS: Exenatide improved glycaemic control by around 1%, and had the added benefit of weight loss. The gliptins were effective in improving glycaemic control, reducing HbA1c level by about 0.8%. Glargine and detemir were equivalent to Neutral Protamine Hagedorn (NPH) (and to each other) in terms of glycaemic control but had modest advantages in terms of hypoglycaemia, especially nocturnal. Detemir, used only once daily, appeared to cause slightly less weight gain than glargine. The glitazones appeared to have similar effectiveness in controlling hyperglycaemia. Both can cause heart failure and fractures, but rosiglitazone appears to slightly increase the risk of cardiovascular events whereas pioglitazone reduces it. Eight trials examined the benefits of adding pioglitazone to an insulin regimen; in our meta-analysis, the mean reduction in HbA1c level was 0.54% [95% confidence interval (CI) -0.70 to -0.38] and hypoglycaemia was marginally more frequent in the pioglitazone arms [relative risk (RR) 1.27, 95% CI 0.99 to 1.63]. In most studies, those on pioglitazone gained more weight than those who were not. In terms of annual drug acquisition costs among the non-insulin regimes for a representative patient with a body mass index of around 30 kg/m2, the gliptins were the cheapest of the new drugs, with costs of between 386 pounds and 460 pounds. The glitazone costs were similar, with total annual costs for pioglitazone and for rosiglitazone of around 437 pounds and 482 pounds, respectively. Exenatide was more expensive, with an annual cost of around 830 pounds. Regimens containing insulin fell between the gliptins and exenatide in terms of their direct costs, with a NPH-based regimen having an annual cost of around 468 pounds for the representative patient, whereas the glargine and detemir regimens were more expensive, at around 634 pounds and 716 pounds, respectively. Comparisons of sitagliptin and rosiglitazone, and of vidagliptin and pioglitazone slowed clinical equivalence in terms of quality-adjusted life-years (QALYs), but the gliptins were marginally less costly. Exenatide, when compared with glargine, appeared to be cost-effective. Comparing glargine with NPH showed an additional anticipated cost of around 1800 pounds. Within the comparison of detemir and NPH, the overall treatment costs for detemir were slightly higher, at between 2700 pounds and 2600 pounds. LIMITATIONS: The UKPDS Outcomes Model does not directly address aspects of the treatments under consideration, for example the direct utility effects from weight loss or weight gain, severe hypoglycaemic events and the fear of severe hypoglycaemic events. Also, small differences in QALYs among the drugs lead to fluctuations in incremental cost-effectiveness ratios. CONCLUSIONS: Exenatide, the gliptins and detemir were all clinically effective. The long-acting insulin analogues glargine and detemir appeared to have only slight clinical advantages over NPH, but had much higher costs and did not appear to be cost-effective as first-line insulins for type 2 diabetes. Neither did exenatide appear to be cost-effective compared with NPH but, when used as third drug after failure of dual oral combination therapy, exenatide appeared cost-effective relative to glargine in this analysis. The gliptins are similar to the glitazones in glycaemic control and costs, and appeared to have fewer long-term side effects. Therefore, it appears, as supported by recent NICE guidelines, that NPH should be the preferred first-line insulin for the treatment of type 2 diabetes. More economic analysis is required to establish when it becomes cost-effective to switch from NPH to a long-acting analogue. Also, long-term follow-up studies of exenatide and the gliptins, and data on combined insulin and exenatide treatment, would be useful.