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

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Insulin 2 endocrinologydiseasesdrugs
acarbose 12 endocrinologydiseasesdrugs
diabetes mellitus 3 endocrinologydiseases
hypoglycemia 29 endocrinologydiseases
metformin 20 endocrinologydiseasesdrugs
type 2 diabetes mellitus 2 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
Insulin 16080 arms in the model.10.1371/journal.pone.0167190.t002Table 2Clinical Input Variables.SAXA+MET aACAR+MET a Insulin cVariableMeanSEMeanSEMeanHbA1c change, %-1.020.11-0.810.07−1.11Weight change, kg-1.880.74-0.260.761.9SBP
Insulin 17527 head-to-head studies [[33],[41]–[44]]. The annual cost of MET was estimated from Hou et al [[51]]. Insulin cost per kilogram weight per day was assumed to be ¥0.137 based on the inherent therapy profile of
acarbose 793 /2016AbstractObjectiveThis 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
acarbose 11443 were inadequately controlled on MET alone.Search terms included “saxagliptin”, “Onglyza”, “ acarbose ” or “Glucobay”, in combination with “type 2 diabetes”, “non-insulin-dependent diabetes mellitus”
acarbose 16517 hypoglycemia0.00040.0013 b0.00020.0009 b0.022Probability gastrointestinal adverse events00 b0.10.02 b0ACAR, acarbose ; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; MET, metformin; SAXA, saxagliptin; SBP,
acarbose 18131 for saxagliptin in eastern China according to Chinese Price Bureau [[49]].b Official drug price for acarbose in eastern China according to Chinese Price Bureau [[50]].c Obtained from Hou et al. [[51]]. The cost
acarbose 23748 2–5.10.1371/journal.pone.0167190.g002Fig 2Simulated progression of HbA1c in the treatment (saxagliptin+metformin) and control ( acarbose +metformin) arms over the modeled time horizon.10.1371/journal.pone.0167190.g003Fig 3Simulated progression
acarbose 23932 horizon.10.1371/journal.pone.0167190.g003Fig 3Simulated progression of body weight in the treatment (saxagliptin+metformin) and control ( acarbose +metformin) arms over the modeled time horizon.10.1371/journal.pone.0167190.g004Fig 4Simulated progression
acarbose 24108 horizon.10.1371/journal.pone.0167190.g004Fig 4Simulated progression of SBP in the treatment (saxagliptin+metformin) and control ( acarbose +metformin) arms over the modeled time horizon.10.1371/journal.pone.0167190.g005Fig 5Simulated progression
acarbose 24292 horizon.10.1371/journal.pone.0167190.g005Fig 5Simulated progression of cholesterol in the treatment (saxagliptin+metformin) and control ( acarbose +metformin) arms over the modeled time horizon.10.1371/journal.pone.0167190.t007Table 7Base Case Results
acarbose 25671 Life Years15.58715.6080.02Cost per QALYDominates−38,640Cost per Life YearDominates−918,030ACAR, acarbose ; BMI, body mass index; LY, life-year; MET, metformin; QALY, quality-adjusted life-year; SAXA, saxagliptin.a
acarbose 29861 complications costs−18,7290.48−38,626Probabilistic sensitivity analysis−21,9990.47−46,815ACAR, acarbose ; BMI, body mass index; GI, gastrointestinal; HbA1c, glycated hemoglobin; ICER, incremental cost-effectiveness
acarbose 32286 incremental cost-effectiveness ratios for the treatment (saxagliptin+metformin) arm versus control ( acarbose +metformin) arm with a CE threshold value of ¥46,629 (GDP per capita in China in 2014).10.1371/journal.pone.0167190.g008Fig
acarbose 32521 8Cost effectiveness acceptability curve for the treatment (saxagliptin+metformin) arm versus control ( acarbose +metfromin) arm.DiscussionThis is the first economic evaluation study using the Cardiff Diabetes Model
metformin 765 (collection): /2016AbstractObjectiveThis 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)
metformin 802 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.MethodsSystematic
metformin 3781 insulin; weight gain with insulin, SUs, and thiazolidinediones; gastrointestinal [GI] discomfort with metformin [MET], α-glucosidase inhibitors [AGIs], and glucagon-like peptide-1 [GLP-1] receptor agonists) [[4]–[6]]
metformin 16591 events00 b0.10.02 b0ACAR, acarbose; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein; MET, metformin ; SAXA, saxagliptin; SBP, systolic blood pressure; SE, standard error.a Variables were taken from five
metformin 18246 eastern China according to Chinese Price Bureau [[50]].c Obtained from Hou et al. [[51]]. The cost for metformin is ¥366.9 per 12 weeks, and thus the cost of metformin = 366.9x 4 = 1467.6. Convert to 2014 yuan using
metformin 18302 Obtained from Hou et al. [[51]]. The cost for metformin is ¥366.9 per 12 weeks, and thus the cost of metformin = 366.9x 4 = 1467.6. Convert to 2014 yuan using the Chinese Consumer Price Index from 2013 to 2014,
metformin 18427 1467.6. Convert to 2014 yuan using the Chinese Consumer Price Index from 2013 to 2014, annual cost of metformin = 1577.28.Costs associated with diabetes-related complications were split into fatal or nonfatal costs,
metformin 23724 2–5.10.1371/journal.pone.0167190.g002Fig 2Simulated progression of HbA1c in the treatment (saxagliptin+ metformin ) and control (acarbose+metformin) arms over the modeled time horizon.10.1371/journal.pone.0167190.g003Fig
metformin 23757 2–5.10.1371/journal.pone.0167190.g002Fig 2Simulated progression of HbA1c in the treatment (saxagliptin+metformin) and control (acarbose+ metformin ) arms over the modeled time horizon.10.1371/journal.pone.0167190.g003Fig 3Simulated progression of body
metformin 23908 horizon.10.1371/journal.pone.0167190.g003Fig 3Simulated progression of body weight in the treatment (saxagliptin+ metformin ) and control (acarbose+metformin) arms over the modeled time horizon.10.1371/journal.pone.0167190.g004Fig
metformin 23941 3Simulated progression of body weight in the treatment (saxagliptin+metformin) and control (acarbose+ metformin ) arms over the modeled time horizon.10.1371/journal.pone.0167190.g004Fig 4Simulated progression of SBP
metformin 24084 horizon.10.1371/journal.pone.0167190.g004Fig 4Simulated progression of SBP in the treatment (saxagliptin+ metformin ) and control (acarbose+metformin) arms over the modeled time horizon.10.1371/journal.pone.0167190.g005Fig
metformin 24117 horizon.10.1371/journal.pone.0167190.g004Fig 4Simulated progression of SBP in the treatment (saxagliptin+metformin) and control (acarbose+ metformin ) arms over the modeled time horizon.10.1371/journal.pone.0167190.g005Fig 5Simulated progression of cholesterol
metformin 24268 horizon.10.1371/journal.pone.0167190.g005Fig 5Simulated progression of cholesterol in the treatment (saxagliptin+ metformin ) and control (acarbose+metformin) arms over the modeled time horizon.10.1371/journal.pone.0167190.t007Table
metformin 24301 5Simulated progression of cholesterol in the treatment (saxagliptin+metformin) and control (acarbose+ metformin ) arms over the modeled time horizon.10.1371/journal.pone.0167190.t007Table 7Base Case Results for Saxagliptin
metformin 25723 QALYDominates−38,640Cost per Life YearDominates−918,030ACAR, acarbose; BMI, body mass index; LY, life-year; MET, metformin ; QALY, quality-adjusted life-year; SAXA, saxagliptin.a Treatment cost included cost of insulin and cost
metformin 29992 GI, gastrointestinal; HbA1c, glycated hemoglobin; ICER, incremental cost-effectiveness ratio; MET, metformin ; QALY, quality-adjusted life-year; SAXA, saxagliptin.*Analysis based on 1000 patients. Everything else
metformin 32255 PSA.10.1371/journal.pone.0167190.g007Fig 7Scatter plot of incremental cost-effectiveness ratios for the treatment (saxagliptin+ metformin ) arm versus control (acarbose+metformin) arm with a CE threshold value of ¥46,629 (GDP per capita in
metformin 32295 incremental cost-effectiveness ratios for the treatment (saxagliptin+metformin) arm versus control (acarbose+ metformin ) arm with a CE threshold value of ¥46,629 (GDP per capita in China in 2014).10.1371/journal.pone.0167190.g008Fig
metformin 32490 2014).10.1371/journal.pone.0167190.g008Fig 8Cost effectiveness acceptability curve for the treatment (saxagliptin+ metformin ) arm versus control (acarbose+metfromin) arm.DiscussionThis is the first economic evaluation study using
Select Disease Character Offset Disease Term Instance
diabetes mellitus 855 saxagliptin+metformin (SAXA+MET) versus acarbose+metformin (ACAR+MET) in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on MET alone.MethodsSystematic literature reviews were performed to identify
diabetes mellitus 2790 third of the world’s diabetic population by the year 2025 [[2]]. The number of people with type 2 diabetes mellitus (T2DM) is increasing worldwide [[1]]. In China in 2014, there were approximately 96 million adult diabetics
diabetes mellitus 11542 “acarbose” or “Glucobay”, in combination with “type 2 diabetes”, “non-insulin-dependent diabetes mellitus ” or “T2DM”, and “Chinese” or “China” (Detailed search strategies are provided in S1 Table).
hypoglycemia 1434 over a patient’s lifetime.ResultsSAXA+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,
hypoglycemia 3637 decades. Despite the proven efficacy of these antidiabetic drugs, their nonnegligible adverse effects ( hypoglycemia with sulfonylureas [SUs] and insulin; weight gain with insulin, SUs, and thiazolidinediones; gastrointestinal
hypoglycemia 5332 concentrations after a carbohydrate load [[5],[22]]. ACAR lowers postprandial glucose levels without causing hypoglycemia and malabsorption, is generally safe and well tolerated [[23]–[25]], and may provide beneficial cardiovascular
hypoglycemia 6432 postprandial glucose and is generally safe and well tolerated. Additionally, it confers a low risk of hypoglycemia , weight gain, and cardiovascular events [[28]–[31]] and provides the additional advantages of fewer
hypoglycemia 10415 [[5],[40]]. The model also allowed for customization of adverse events in each therapy arm. For each hypoglycemia event and adverse event, the model evaluated the probability of that event occurring and the associated
hypoglycemia 15187 treatment-induced impacts on HbA1c, body weight, SBP and cholesterol; and rates of adverse events, including hypoglycemia and GI adverse events, were also evaluated for each arm. These data were obtained from meta-analysis
hypoglycemia 15524 model, but all the head-to-head studies did not clearly differentiate between symptomatic and severe hypoglycemia episodes. Therefore, we estimated that a rate of 2.18% represented the proportion of severe cases out
hypoglycemia 15646 Therefore, we estimated that a rate of 2.18% represented the proportion of severe cases out of all hypoglycemia events [[40]]. The efficacy of insulin therapy used the inherent therapy profile of the Cardiff model
hypoglycemia 16348 change, mmol/l-0.230.22-0.130.120HDL cholesterol change, mmol/l0.060.050.010.050Probability symptomatic hypoglycemia 0.0180.009 b0.0090.0064 b0.616Probability severe hypoglycemia0.00040.0013 b0.00020.0009 b0.022Probability
hypoglycemia 16409 mmol/l0.060.050.010.050Probability symptomatic hypoglycemia0.0180.009 b0.0090.0064 b0.616Probability severe hypoglycemia 0.00040.0013 b0.00020.0009 b0.022Probability gastrointestinal adverse events00 b0.10.02 b0ACAR, acarbose;
hypoglycemia 19639 obtained from hospital survey and other published studies [[53]–[54]].The treatment cost of severe hypoglycemia (¥3829.96) was abstracted from Zheng et al, which investigated direct medical costs for episodes of
hypoglycemia 19753 (¥3829.96) was abstracted from Zheng et al, which investigated direct medical costs for episodes of hypoglycemia in China [[40]]; treatment costs of GI adverse events were assumed to be 0 because published evidence
hypoglycemia 21269 [[56]], excluding end-stage renal disease (ESRD) and blindness [[57]], BMI-related changes [[58]], hypoglycemia episodes [[59]], and GI adverse events [[60]] which were obtained from other studies (Table 6).10.1371/journal.pone.0167190.t006Table
hypoglycemia 21706 failure0.1080.108Stroke0.1640.164Blindness0.0740.074End-stage renal disease0.2630.263Amputation0.2800.280Ulcer0.0590.059Symptomatic hypoglycemia 0.01420.000Severe hypoglycemia0.0470.000Gastrointestinal adverse events0.040.000BMI-related changes Per
hypoglycemia 21736 renal disease0.2630.263Amputation0.2800.280Ulcer0.0590.059Symptomatic hypoglycemia0.01420.000Severe hypoglycemia 0.0470.000Gastrointestinal adverse events0.040.000BMI-related changes Per unit decrease in BMI0.01710.0171 Per
hypoglycemia 22049 the UKPDS 62 study [[56]]; end-stage renal disease and blindness [[57]], BMI-related changes [[58]], hypoglycemia [[59]], and GI adverse events [[60]] were obtained from other studies.Sensitivity analysesThe impacts
hypoglycemia 22938 the base case analysis, the SAXA+MET cohort predicted lower incidences of most cardiovascular events, hypoglycemia events and fatal events as compared with that of the ACAR+MET cohort. Consistent with the differences
hypoglycemia 23398 higher in SAXA+MET, this disadvantage was offset by its much lower BMI-related prescription costs and hypoglycemia costs as compared with ACAR+MET. Overall, SAXA+MET was associated with lower total costs than that of
hypoglycemia 29357 ¥200−18,7560.48−38,681Cost of GI adverse events set to be ¥1000−18,8360.48−38,847Cost of severe hypoglycemia doubled−18,8130.48−38,798GI adverse events in ACAR+MET doubled−18,7360.49−38,330Utility decrement
hypoglycemia 29541 doubled−18,7360.49−38,330Utility decrement of GI adverse events doubled−18,7360.49−38,329Probability of hypoglycemia of SAXA+MET equal to ACAR+MET−18,7370.49−38,622Utility decrement of hypoglycemia doubled−18,7360.49−37,961Discount
hypoglycemia 29626 doubled−18,7360.49−38,329Probability of hypoglycemia of SAXA+MET equal to ACAR+MET−18,7370.49−38,622Utility decrement of hypoglycemia doubled−18,7360.49−37,961Discount rate (costs and benefits) 3.5%−17,6470.46−38,180Alternative
hypoglycemia 30736 SAXA+MET gained more dominance over ACAR+MET as compared with that of the base case. GI adverse events and hypoglycemia were commonly observed in the treatment of T2DM, which might have an effect on both cost and utility.
hypoglycemia 30895 T2DM, which might have an effect on both cost and utility. Alternative treatment costs of GI events or hypoglycemia in the sensitivity analyses, resulting in a little changes in cost saving gained by SAXA+MET compared
hypoglycemia 31078 saving gained by SAXA+MET compared to that of base case. When GI adverse events in ACAR+MET doubled or hypoglycemia of SAXA+MET equal to ACAR+MET, the incremental QALYs gained by SAXA+MET increased from 0.48 to 0.49.
hypoglycemia 34486 (modest glucose control and neutral effects on weight) and were well tolerated, with lower risk of hypoglycemia and other adverse events, whereas AGIs were associated with frequent GI adverse events and a frequent
hypoglycemia 35136 need to minimize adverse events [[6]]. In this study, sensitivity analyses on GI adverse events and hypoglycemia had demonstrated the influence of adverse events on the incremental QALYs and cost savings. Our study
hypoglycemia 35452 evaluating T2DM treatments; there is also an urgent need to minimize adverse events. Adverse events, such as hypoglycemia , weight gain and GI symptoms, may interfere with the attainment of stringent blood glucose control,
hypoglycemia 37796 costs.SAXA is a well-tolerated drug that effectively controls blood glucose levels and has a low risk of hypoglycemia , weight gain, and GI adverse events, making it possible to increase patient QOL and allow for better
hypoglycemia 38977 investigated in our study, which neglected the considerable indirect costs of diabetes-related events ( hypoglycemia , weight gain, GI adverse events) on productivity. Moreover, total costs in the ACAR+MET cohort were
type 2 diabetes mellitus 848 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.MethodsSystematic literature reviews were performed to identify
type 2 diabetes mellitus 2783 almost a third of the world’s diabetic population by the year 2025 [[2]]. The number of people with type 2 diabetes mellitus (T2DM) is increasing worldwide [[1]]. In China in 2014, there were approximately 96 million adult diabetics

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