| BackgroundThe prevalence of diabetes is increasing year by year.As one of the major chronic diseases,diabetes is one of the most serious public health problems in the world,it is a serious threat to the health of the world’s people.According to the survey data of the International Diabetes Federation(IDF),the prevalence of Diabetes among people aged 20-70 was 9.3%in 2019,and the number of people with Diabetes was 463 million.By 2030,the prevalence rate will rise to 10.2%.The number of people with Diabetes would be 578 million.According to the IDF partition,the Western Pacific region,including China,had the highest number of diabetes among people aged 20-70 in 2019,it was 163 million.The disease burden of diabetes is severe.Multiple studies have shown that the occurrence of various complications in late stage of diabetes will bring catastrophic economic losses to patients and their families.According to IDF data,from 1990 to 2015,the proportion of deaths caused by diabetes in the total death of our citizens increased from 0.84%to 1.47%,and diabetes has become the fifth disease caused of our citizens in death.The health expenses of diabetic patients in China are high and increasing rapidly.In 2015,the total economic burden of middle-aged and elderly patients diagnosed with diabetes was 259.86 billion yuan,accounting for 0.38%of GDP in the same period.It is estimated that the health expenses related to diabetes in China may reach us $376 billion by 2030.The prevention and treatment strategy of diabetes is the comprehensive prevention and treatment measures including diet treatment,reasonable exercise,condition monitoring,drug,health education,psychological counseling,and complications prevention.Timely and reasonable drug treatment can not only delay the progression of diabetes,but also reduce the occurrence of costly complications,reduce the death rate and Improve patients’ quality of life.Vigliptin is the first DPP-4 inhibitor successfully developed in the world,which was listed in China in February 2012.Vigliptin can be used throughout the treatment of patients with diabetes and is one of the most widely indicated DPP-4 inhibitors in China.It has been recommended as second-line drugs for type 2 diabetes in evidence-based clinical guidelines issued by The American Diabetes Association(ADA),the European Diabetes Society(EASD)and the Diabetes Branch of The Chinese Medical Association.Through literature retrieval and analysis,the incidence of adverse reactions in the treatment of type 2 diabetes mellitus was low and the treatment effect was better,however,systematic evaluation of its safety and effectiveness is less.During clinical treatment,doctors and patients often regard safety and effectiveness as the main criteria for drug selection.For diabetes and other chronic non-communicable diseases,patients often need to take long-term medication,so economy has become one of the factors it must pay attention to.The economic evaluation of vigliptin in treatment of type 2 diabetes are few studies by domestic and foreign scholars,there are even fewer studies based on real world data,which have not been found until the time of writing this paper.It is not conducive for doctors and patients to make reasonable decisions about the use of vigliptin in the long-term treatment of type 2 diabetes.Objectives(1)To understand the treatment status of type 2 diabetes in China,According to the management guidelines for clinical comprehensive evaluation of drugs,to evaluate the safety,efficacy and economy of vigliptin+metformin in treatment of type 2 diabetes mellitus.To evaluate the safety and efficacy of vigliptin+metformin in treatment of type 2 diabetes mellitus(2)To collect clinical efficacy indicators through a prospective observational cohort study of vigliptin in the treatment of type 2 diabetes mellitus in the real world.To get the Loss of health utility due to diabetes complications and health utility of diabetic patients through field investigation.To evaluate the long-term cost-effectiveness of vigliptin+metformin vs a glycosidase inhibitor acarbose+metformin in the treatment of type 2 diabetes By Cardiff in type 2 diabetes model and quantify the long-term impact of vigliptin+metformin on reducing the socioeconomic burden of Chinese patients with type 2 diabetes mellitus,compared with the a glycosidase inhibitor acarbose+metformin(3)To summarize the advantages and disadvantages of the safety,efficacy and economy of vigliptin+ metformin in the treatment of type 2 diabetes mellitus,and provide basis for clinical decision,Diabetes management and policy development.Methods(1)Through literature research,the status quo of diabetes drug therapy was understood,Emphasis was placed on the status quo of vigliptin+metformin in the treatment of type 2 diabetes mellitus,mainly including its safety,effectiveness and cost-effectiveness etc.And the research progress and shortcomings of vigliptin in the treatment of type 2 diabetes mellitus was summarized.(2)Based on the literature review,the systematic review about the effectiveness and safety of vigliptin+metformin in the treatment of type 2 diabetes mellitus were conducted through meta-analysis.(3)A prospective observational study in the real world collected the clinical efficacy and baseline characteristics of patients with type 2 diabetes mellitus who were treated with the vigliptin+metformin or the α glycosidase inhibitor acarbose+metformin when single oral antidiabetic drug was failure.(4)Through questionnaire survey,according to the quality of life questionnaire for diabetics,the hospitalized diabetic patients in the Affiliated Hospital of Qingdao University and Yantai Mountain Hospital from July 2019 to July 2021 were investigated.Eq-5d-51 scale was used to measure the health utility of diabetic patients and their complications and the utility loss caused by complications.At the same time,social demographic information such as gender and age,and clinical information such as onset duration and complications,and the occurrence of hypoglycemia were investigated.(5)The Cardiff type 2 diabetes model was used to evaluate the long-term cost-effectiveness of vigliptin+ metformin VS alpha glucosidase inhibitor acarbose+metformin in the treatment of type 2 diabetes mellitus,and to simulate and predict disease progression,complications and death events.Results(1)Good safety and effectiveness of vigliptin in the treatment of type 2 diabetes mellitus3 studies and 1448 patients with type 2 diabetes mellitus were included in the meta-analysis,the results of the meta-analysis showed that the random-effect model was used to evaluate the efficacy of vigliptin+metformin in the treatment of type 2 diabetes mellitus.The "vigliptin combined with metformin" group was superior to the "α-glycosidase inhibitor combined with metformin" group in reducing HbAlc level,the difference was statistically significant[WMD=-0.26,95%CI(-0.43,-0.13),P=0.002].In terms of the safety of vigagliptin+metformin in the treatment of type 2 diabetes mellitus,a random-effect model was used.The results of Meta-analysis showed that①the incidence of adverse reactions in type 2 diabetes patients in the "vigagliptin+metformin"group was lower than that in the "α-glycosidase inhibitor+ metformin" group.The difference was statistically significant[RR=0.49,95%CI(0.36,0.67),P<0.001].① In terms of the incidence of hypoglycemia,Using a fixed-effect model,meta-analysis results showed that the incidence of hypoglycemia in type 2 diabetes patients in the "vigliptin+metformin" group was lower than that in the"α-glycosidase inhibitor+metformin" group,the difference was statistically significant[RR=0.24,95%CI(0.08,0.69),P=0.008].③In terms of the incidence of body weight gain(≥3%),Using a fixed-effect model,meta-analysis showed that the incidence of weight gain(≥3%)in patients with type 2 diabetes in the"vigliptin+metformin" group was lower than that in the"α-glycosidase inhibitor+metformin" group,the difference was statistically significant[RR=0.57,95%CI(0.43,0.77),P<0.001].④ In terms of the incidence of gastrointestinal dysfunctions,a random-effect model was used.Meta-analysis results showed that there was no significant difference in the incidence of gastrointestinal dysfunctions in type 2 diabetes patients in the"vigliptin+metformin" group compared with "α-glycosidase inhibitor+metformin"group[RR=0.50,95%CI(0.23,1.09),P=0.082).(2)Health utility value of type 2 diabetes patientsEq-5d-51 scale was used to investigate the health status of 1194 patients with type 2 diabetes.It was found that the average health utility value of patients without diabetes complications was 0.94±0.006,and the average health utility value of patients with diabetes complications was 0.838±0.009.The health utility values is from 0.312±0.137 to 0.852±0.036 in different complication states:Ischemic heart disease is 0.802±0.023,myocardial infarction is 0.764±0.062,congestive heart failure is 0.718±0.121,stroke is 0.853±0.036,blindness is 0.844±0.014,end-stage renal disease is 0.792±0.031,ulcers is 0.547±0.041,amputation is 0.312 ± 0.137.Overall,the health utility value of diabetic patients with complications was lower than that of patients without complications,except for congestive heart failure and stroke,the differences in other groups were statistically significant(P<0.05).Meanwhile,the health utility in occupational,education,income and disease course was statistically significant(P<0.05).Different complications had different effects on quality of life,and the loss of health utility value was from 0.031±0.024 to 0.488±0.186.Ischemic heart disease is 0.103±0.033,acute myocardial infarction is 0.203±0.072,congestive heart failure is 0.154±0.109,stroke is 0.08±0.055,blindness is 0.31±0.024,end-stage renal disease is 0.082±0.034,ulcers is 0.357±0.039,amputation is 0.488±0.186.(3)Economics of vigliptin in the treatment of type 2 diabetes mellitus① Results of Cardiff type 2 diabetes model based on mean simulationIn terms of clinical efficacy,the survival trend of patients in the vigliptin +metformin group and the acarbose+metformin group are consistent.Specifically,After 50 years,2000 people simulated the operation,more than half of patients(>1000)survived more than 25 years.Meanwhile the vigliptin+metformin group is more effective in reducing HbAlc,weight,and SBP risk levels.In terms of diabetes-related complications,the predicted number of diabetes-related complications and deaths in the vigliptin+metformin group is generally lower than that in the acarbose+metformin group.It can reduce 6.949 myocardial infarction events,1.043 heart failure events,and 3.359 stroke events,3.467 blindness events,3.121 amputation events,2.058 ulcers events,3.176 event-related deaths and 5.639 diabetes-related deaths.But there was an increase of 0.221 ischemic heart disease events.In terms of diabetes treating-related costs,the vigliptin+metformin group is expected to save a total cost of 2026860.617 yuan compared with the acarbose+metformin group.Specifically,It saves 590474.848 yuan of costs related to myocardial infarction events,25429.763 yuan of costs related to heart failure events,18203.978 yuan of costs related to stroke events,249002.223 yuan of costs related to blindness events,99273.513 yuan of costs related to amputation events and 2388918.770 yuan of costs related to BMI.However,the cost of ischemic heart disease event increases by 4647.582 yuan,and the drug treatment cost increases by 1501564.889 yuan.In terms of cost-effectiveness ratio,compared with acarbose+metformin,vigliptin+metformin group reduced cost by 2026860.617 yuan,increased quality adjusted life years by 76.596QALYs,and gained an additional 39.162 life years.ICER is-26461.690 yuan/QALY,and the cost of each additional life year is-51755.371 yuan.In terms of sensitivity analysis,the results of single-factor sensitivity analysis shows that the patient’s baseline demographic characteristics,clinical baseline characteristics,health utility,and discount rate have a significant impact on the incremental cost,incremental QALYs and ICER of vigliptin+metformin group compared with acarbose+metformin group.② Results of Cardiff type 2 diabetes model simulation based on individual patient dataIn terms of clinical efficacy,the survival rate of patients in the vigagliptin+metformin group was generally higher than in the acarbose+group.After 50 years,2000 people simulated the operation,The median survival time of patients in the vigagliptin+metformin group was about 26 years,while the median survival time of patients in the acarbose+metformin group was about 23 years.Meanwhile the vigliptin+metformin group was more effective in reducing HbAlc,weight,and SBP risk levels.In terms of diabetes-related complications,the predicted number of diabetes-related complications and deaths was generally higher in the vigliptin+metformin group than in the acarbose+metformin group.It can increase 28.012 myocardial infarction events,42.944 myocardial infarction events,3.636 heart failure events,19.942 stroke events,9.447blindness events,20.283amputation events,7.091 ulcers events,25.266 event-related deaths and 36.354 diabetes-related deaths.But it can reduce 49.765 other causes-relate deaths.In terms of diabetes treating-related costs,the vigliptin+metformin group is expected to increase the total cost of 54945859.022 yuan compared with the acarbose+metformin group.Specifically,it can increase 696279.498 yuan of costs related to ischemic heart disease events,1799747.813 yuan of costs related to myocardial infarction events,7822.274 yuan of costs related to stroke events,306847.349yuan of costs related to blindness events,222745.680 yuan of the cost related to amputation events,50421912.737 yuan of the cost related to BMI events.And the drug treatment cost increases by 1505958.417 yuan.But it can reduce15454.744 yuan of the cost related to heart failure events.In terms of cost-effectiveness ratio,compared with acarbose+metformin,vigliptin+metformin group increased cost by 54945853.581yuan,the quality-adjusted life years increased by 1955.680 QALYs,and gained an additional 2105.936 life years.The cost of each additional life year is 26090.937 yuan,and ICER is 28095.540 yuan/QALY,which is lower than 1 times GDP per capita in 2021(80,643.75 yuan).In terms of sensitivity analysis,the results of single-factor sensitivity analysis shows that the patient’s baseline demographic characteristics,clinical baseline characteristics,health utility,and discount rate have a significant impact on the incremental cost,incremental QALYs and ICER of vigliptin+metformin group compared with acarbose+metformin group.Conclusions and SuggestionsBased on real world data,this study analyzed the efficacy and safety of vigagliptin+metformin in the treatment of type 2 diabetes mellitus through meta-analysis and Cardiff type 2 diabetes model,and simulated the long-term cost and effect of vigagliptin+metformin in the treatment of type 2 diabetes mellitus.Eq-5d-51 scale was used to investigate the health utility of diabetic patients and their complications,and the health utility loss value caused by diabetic complications was analyzed by regression.Main conclusions are drawn:(1)Vigliptin+metformin has good efficacy and safety in the treatment of type 2 diabetes mellitus.It can significantly reduce the level of HbA1c,and the overall incidence of adverse reactions is low,especially in the incidence of hypoglycemia.(2)In the long-term treatment of type 2 diabetes,vigliptin+metformin has a good clinical effect in the treatment of type 2 diabetes mellitus,which can better reduce the mortality of patients.The advantages and disadvantages about the prevention of diabetes-related complications and death still need to be further studied.It has economic advantages in terms of long-term cost expenditure and cost-effectiveness and should be recommended as a priority in clinical application.Centralized drug procurement can greatly reduce the disease burden of patients,and has a great influence on ICER value.(3)Gender,occupation,education level,current residence,main form of medical insurance,annual family income and duration of diabetes are all influential factors of the utility value of diabetes patients.Complications had a negative influence on the health utility value of diabetic patients,and the influence of diabetes course on the health utility value has a negative increasing trend.Based on the conclusions of this study,we suggest:(1)Encourage the use of vigliptin+metformin in the second-line treatment of type 2 diabetes mellitus.(2)Strengthen the application of pharmacoeconomic evidence in clinical rational use of type 2 diabetes mellitus.(3)Strengthen the application of research based on real world data in drug comprehensive evaluation(4)Strengthen the prevention and control of diabetes for key groups,improve the quality of life,and reduce the burden of disease(5)Strengthen the concentrated bidding purchase of medicines and reduce the burden of disease on patients... |
PDF Full Text Request